bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexistence of Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes and Pancreatitis
Authors: Zhang Amy L. , Wang Fang , Chang Lee-Shing , McDonnell Marie E. , Min Le
Published: April 2021

Autoimmune diabetes is a rare but severe endocrine toxicity induced by immune checkpoint inhibitor (ICI) treatment. It is unclear if ICI causes selective islet toxicity or non-selective pancreas toxicity. We analyzed 11 patients treated with ICI who developed ICI-related autoimmune diabetes. Eight patients had lipase and/or amylase tested on the same day of diagnosis of autoimmune diabetes. Among them, 75% (6/8) had normal lipase and 100% (6/6) had normal amylase. There was no correlation between glucose level at onset and biochemical pancreatitis. We characterized the clinical features of ICI-induced autoimmune diabetes. Fifty-five percent (6/11) of patients tested positive for GAD65 autoantibodies, and 55% (6/11) developed diabetic ketoacidosis at manifestation of hyperglycemia. In all 11 patients, C-peptide levels were low in the presence of hyperglycemia. ICI-induced thyroiditis was found in 64% (7/11), of which 36% (4/11) were newly diagnosed with thyroiditis while the remaining 27% (3/11) had pre-existing hypothyroidism followed by ICI-induced thyroiditis. Additionally, 27% (3/11), developed ICI-induced hypophysitis. Thyroiditis and autoimmune diabetes coexisted in all patients with ICI-induced hypophysitis. The median time from ICI treatment to the onset of autoimmune diabetes was 11 weeks. Our data suggest that few patients had coexistent ICI-induced autoimmune diabetes and pancreatitis, suggesting ICI mainly caused selective islet toxicity.
Characteristics, Treatment, Outcomes, and Survival in Neuroendocrine G1 and G2 Pancreatic Tumors: Experiences From a Single Tertiary Referral Center
Authors: Calissendorff Jan , Bjellerup-Calissendorff Freja , Bränström Robert , Juhlin C. Christofer , Falhammar Henrik
Published: April 2021

Purpose

Neuroendocrine tumors of the pancreas (Pan-NETs) are usually hormonally inactive with a capacity to metastasize. Since Pan-NETs are rare, more knowledge is needed.

Methods

We reviewed all patients’ medical files with Pan-NET treated at a tertiary center (2006-2019). Grade 1 (G1) and grade 2 (G2) tumors were compared. The latter group was subdivided arbitrarily based on proliferation index into G2a (3-9.9%) and G2b (10-19.9%).

Results

We found 137 patients (76 females, 61 males; G1 n=66, G2 n=42), the median age at diagnosis 61 years (interquartile range (IQR) 50–71), and tumor size 2 cm (1.3–5 cm). The initial surgery was performed in 101 patients. The remaining (n=36) were followed conservatively. Metastatic disease was evident in 22 patients (16%) at diagnosis while new lesions developed in 13 out of 22 patients (59%). In patients without previous metastatic disease, progressive disease was discovered in 29% of G1 vs. 55% of G2 patients (P=0.009), 47% of G2a vs. 75% of G2b patients (NS). Survival was poorer in patients with metastasis at diagnosis vs. those with local disease (P<0.001). During follow-up of 74 months, Pan-NET related death was found in 10 patients. Survival was not different between G1 vs. G2 or G2a vs. G2b, or if tumors were functional. Size ≤2 cm was associated with a better outcome (P=0.004). During the follow-up of small tumors (≤2 cm, n=36) two were resected.

Conclusion

In small non-functional Pan-NETs, active surveillance is reasonable. Progressive disease was more common in G2, but survival was similar in G1, G2 and between G2 subgroups. Survival was poorer in patients with metastasis at diagnosis.
Efficacy of Weight Reduction on Pediatric Nonalcoholic Fatty Liver Disease: Opportunities to Improve Treatment Outcomes Through Pharmacotherapy
Authors: Friesen Chance S. , Hosey-Cojocari Chelsea , Chan Sherwin S. , Csanaky Iván L. , Wagner Jonathan B. , Sweeney Brooke R. , Friesen Alec , Fraser Jason D. , Shakhnovich Valentina
Published: April 2021

Obesity is the single greatest risk factor for nonalcoholic fatty liver disease (NAFLD). Without intervention, most pediatric patients with NAFLD continue to gain excessive weight, making early, effective weight loss intervention key for disease treatment and prevention of NAFLD progression. Unfortunately, outside of a closely monitored research setting, which is not representative of the real world, lifestyle modification success for weight loss in children is low. Bariatric surgery, though effective, is invasive and can worsen NAFLD postoperatively. Thus, there is an evolving and underutilized role for pharmacotherapy in children, both for weight reduction and NAFLD management. In this perspective article, we provide an overview of the efficacy of weight reduction on pediatric NAFLD treatment, discuss the pros and cons of currently approved pharmacotherapy options, as well as drugs commonly used off-label for weight reduction in children and adolescents. We also highlight gaps in, and opportunities for, streamlining obesity trials to include NAFLD assessment as a valuable, secondary, therapeutic outcome measure, which may aid drug repurposing. Finally, we describe the already available, and emerging, minimally-invasive biomarkers of NAFLD that could offer a safe and convenient alternative to liver biopsy in pediatric obesity and NAFLD trials.
Maternal Serum Angiopoietin-Like 3 Levels in Healthy and Mild Preeclamptic Pregnant Women
Authors: Garces María Fernanda , Rodriguez - Navarro Haiver Antonio , Buell - Acosta Julieth Daniela , Burgos - Cardenas Alvaro Javier , Franco - Vega Roberto , Maldonado - Acosta Luis Miguel , Eslava - Schmalbach Javier , Parada - Baños Arturo José , Castro - Pinzon Andres , Sanchez Elizabeth , Angel - Muller Edith , Lacunza Ezequiel , Castaño Justo P. , Dieguez Carlos , Nogueiras Rubén , Ruiz - Parra Ariel Ivan , Caminos Jorge Eduardo
Published: April 2021

Objective

Angiopoietin-like protein 3(ANGPTL3) is an important regulator of lipoprotein metabolism in the fed state by inhibiting the enzyme lipoprotein lipase in oxidative tissues. However, the possible role of ANGPTL3 throughout gestation and its relationship with hormonal and biochemical variables are still unknown. The aim of this study was to determinate serum ANGPTL3 level in healthy non-pregnant women, during healthy and preeclamptic pregnancy and postpartum.

Methods

Serum ANGPTL3 was analyzed by enzyme-linked immunosorbent assay (ELISA), in a prospective cohort of healthy pregnant women (n = 52) and women with mild preeclampsia (n = 21), and women at three months postpartum (n = 20) and healthy non-pregnant women (n = 20). The results obtained were correlated with biochemical, hormonal and anthropometric variables and insulin resistance indices.

Results

Levels of ANGPTL3 were not different between the follicular and the luteal phases of the cycle in healthy non-pregnant women. There was a significant reduction in serum ANGPTL3 levels from the first to the third trimester in healthy pregnant women compared with healthy non-pregnant and postpartum women (p <0.01). ANGPTL3 levels do not differ significantly during the three trimesters of pregnancy neither in healthy women nor in preeclamptic women. The serum levels of ANGPTL3 in women who developed preeclampsia are not statistically different from those observed in healthy pregnant women in each trimester of pregnancy. A significant lineal positive correlation was observed between serum ANGPTL3 levels and triglyceride (P =0.0186, r =0.52), very low-density lipoprotein cholesterol (P =0.0224, r =0.50), and total cholesterol levels (P =0.0220, r =0.50) in healthy non-pregnant women (P 0.05). Besides, there were no significant correlations between serum ANGPTL3 and body mass index (BMI), high-density lipoprotein cholesterol, glucose, insulin, leptin, or HOMA-IR (P >0.05)

Conclusions

We describe for the first time the profile of ANGPTL3 throughout pregnancy and postpartum as well as and discussed about explore their potential contribution interactions with lipoprotein metabolism throughout pregnancy and postpartum. Thus, low levels of ANGPTL3 during pregnancy might favor lipid uptake in oxidative tissues as the main maternal energy source, while may helping to preserve glucose for use by the fetus and placenta.
Non-indigenous and Invasive Freshwater Species on the Atlantic Islands of the Azores Archipelago
Authors: Costa Ana C. , Balibrea Ana , Raposeiro Pedro M. , Santos Sofia , Souto Martin , Gonçalves Vítor
Published: April 2021

Freshwater systems on remote oceanic islands are particularly vulnerable to biological invasions. The case of freshwater ecosystems in the Azores Archipelago is especially relevant considering the islands’ youth and remoteness, and low natural connectivity. This study presents a review of the introduction and presence of non-indigenous freshwater species in the Azores, retrieved from various historical records, paleoenvironmental reconstructions, published records, and field data from two decades of the Water Framework Directive (WFD) monitoring programs. At least 132 non-indigenous freshwater species have successfully established in the Azores, belonging to several taxonomic groups: cyanobacteria (10), synurophytes (1), desmids (1), diatoms (20), plants (41), invertebrates (45), amphibia (2), and fishes (12). Intentional and accidental introductions have been occurring since the establishment of the first human settlers on the archipelago, impacting freshwater ecosystems. The first reported introductions in the Azores were intentional fish stocking in some lakes. Non-deliberate introductions have recently increased through transport-contaminants (51%) associated with the aquarium trade or agricultural products. In the Azores, the highest number of non-indigenous species occur on the largest and most populated island, São Miguel Island (116), followed by Flores (68). Plants constitute the most representative group of introduced species on all islands, but invertebrates, diatoms, and fishes are also well established on most islands. Among invertebrates, non-indigenous arthropods are the most well-established group on all islands except on the smallest Corvo Island. Many non-indigenous species will likely benefit from climate change and magnified by globalization that increases the probability of the movement of tropical and subtropical species to the Azores. Present trends in international trade, importations, and enhanced connectivity of the archipelago by increasing flights and shipping will probably promote the arrival of new species. Augmented connectivity among islands is likely to improve non-indigenous species dispersal within the archipelago as accidental transportation seems to be an essential pathway for non-indigenous freshwater species already present in the Azores.
Restoration of Degraded Alpine Meadows Improves Pollination Network Robustness and Function in the Tibetan Plateau
Authors: Gao Erliang , Wang Yuxian , Bi Cheng , Kaiser-Bunbury Christopher N. , Zhao Zhigang
Published: April 2021

Ecological restoration is widely used to mitigate the negative impacts of anthropogenic activities. There is an increasing demand to identify suitable restoration management strategies for specific habitat and disturbance types to restore interactions between organisms of degraded habitats, such as pollination. In the Tibetan Plateau, alpine meadows have suffered severe degradation due to overgrazing and climate change. Protecting vegetation by fencing during the growing season is a widely applied management regime for restoration of degraded grasslands in this region. Here, we investigated the effect of this restoration strategy on plant–pollinator communities and plant reproduction in the eastern Tibetan Plateau. We collected interaction and seed set data monthly across three grazed (grazed all year) and three ungrazed (fenced during growing season) alpine meadows in growing seasons of two consecutive years. We found ungrazed meadows produced more flowers and attracted more pollinator visits. Many common network metrics, such as nestedness, connectance, network specialization, and modularity, did not differ between grazing treatments. However, plants in ungrazed meadows were more robust to secondary species extinction than those in grazed meadows. The observed changes in the networks corresponded with higher seed set of plants that rely on pollinators for reproduction. Our results indicate that protection from grazing in growing seasons improves pollination network stability and function and thus is a viable restoration approach for degraded meadows.
A Dynamic Modeling Framework to Evaluate the Efficacy of Control Actions for a Woody Invasive Plant, Hakea sericea
Authors: Morais Maria C. , Gonçalves Berta , Cabral João A.
Published: April 2021

Invasive alien species (IAS) are a significant component of global changes, causing severe economic and biodiversity damage. In this regard,Hakea sericeais one of the most widespread IAS throughout the Mediterranean region, including Portugal. The difficulty surrounding its management is exacerbated by post-fire situations, signifying a challenging task for managers. To assist in this effort, we used a system dynamic approach to model the population dynamics ofHakea sericearegarding the combinations of wildfire risk and control scenarios, which differ in periodicity, type of interventions, and cohort age. The ultimate goal of this study was to assess the effectiveness and costs of control efforts at reducing the abundance of this IAS. A Natura 2000 site Alvão/Marão (code PTCON0003) in northern Portugal, severely invaded byHakea sericea, served as the study site. The modeling results demonstrate thatHakea sericeais likely to continue spreading if left uncontrolled. Although it may not be possible to ensure eradication ofHakea sericeafrom the study, repeated control actions aimed at the entire IAS population could be very effective in reducing its area. From a practical standpoint, removing all plants 24 months after each fire event followed by subsequent monitoring appears to be the most cost-effective strategy for managingHakea sericea. Considering the modeling results, the dynamic modeling framework developed is a versatile, instructive tool that can support decision-making aimed at effective management ofHakea sericea.
RNA-Seq Profiling of Circular RNAs During Development of Hindgut in Rat Embryos With Ethylenethiourea-Induced Anorectal Malformations
Authors: Li Si Ying , Wang Chen Yi , Xiao Yun Xia , Tang Xiao Bing , Yuan Zheng Wei , Bai Yu Zuo
Published: April 2021

Anorectal malformations (ARMs) are among the most common congenital terminal digestive tract malformations. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, play roles in the development of the digestive system; however, their contributions to the pathogenesis of ARMs are not well-established. In this study, we explored the mechanism underlying ethylenethiourea (ETU)-induced ARMs by profiling circRNA expression via RNA-seq and constructing a regulatory circRNA-miRNA-mRNA network. Nine pregnant rats were gavage-fed a single dose of 125 mg/kg 1% ETU (ARM group) on gestational day 10 (GD10), and another 9 pregnant rats received a similar dose of saline (normal group) as a control. Embryos were obtained by cesarean section on the key time-points of anorectal development (GD14, GD15, and GD16). Hindgut samples isolated from the fetuses were evaluated by high-throughput sequencing and differentially expressed circRNAs were validated by reverse transcription-quantitative polymerase chain reaction, agarose gel electrophoresis, and Sanger cloning and sequencing. A total of 18295 circRNAs were identified in the normal and ARM groups. Based on the 425 differentially expressed circRNAs (|Fc| > 2, p < 0.05), circRNA-miRNA and miRNA-mRNA pairs were predicted using miREAP, miRanda, and TargetScan. A total of 55 circRNAs (14 up- and 41 downregulated in the ARM group compared to the normal group) were predicted to bind to 195 miRNAs and 947 mRNAs. Competing endogenous RNA networks and a Kyoto Encyclopedia of Genes and Genomes analysis revealed that novel_circ_001042 had the greatest connectivity and was closely related to ARM-associated signaling pathways, such as the Wingless Type MMTV integration site family, mitogen-activated protein kinase, and transforming growth factor-β pathways. These results provide original insight into the roles of circRNAs in ARMs and provide a valuable resource for further analyses of molecular mechanisms and signaling networks.
Institutional and Social Issues Surrounding Genetic Counselors in Japan: Current Challenges and Implications for the Global Community
Authors: Aizawa Yayoi , Watanabe Atsushi , Kato Kazuto
Published: April 2021

In recent years, genetic counseling has started playing a major role in the field of genomic medicine. There are currently about 7,000 genetic counselors in more than 28 countries, with 267 certified genetic counselors in Japan alone (about 2 per million population, as of April 2020). While the rapid advancement of genomic medicine has expanded this field, the challenges genetic counselors face are also evolving. This article aims to provide an overview of the institutional and social issues surrounding genetic counselors in Japan and discuss implications for the global community. In Japan, with the rapid changes in genomic medicine and the establishment of a delivery mechanism within the healthcare system, several issues need to be discussed. First, many genetic testing, counseling, and preventive healthcare programs are not covered by public health insurance. Second, reducing human resource shortages for genetic counseling is an urgent issue. Third, the lack of a national qualification in the profession is critically important issue in the field. Fourth, research on the role and value of genetic counselors is still limited. To address these issues, discussions among relevant stakeholders, including genetic counselors, professionals in genomic medicine, and lawmakers, are necessary. Additionally, we believe that research by genetic counselors to evaluate and improve their practice and examine institutional and social issues is crucial for developing their profession’s activities and delivering high-quality healthcare to many people. To establish the position and role of the relatively new profession of genetic counselor, sharing information and collaborating on institutional and social challenges faced by genetic counselors globally will be beneficial.
NEPdb: A Database of T-Cell Experimentally-Validated Neoantigens and Pan-Cancer Predicted Neoepitopes for Cancer Immunotherapy
Authors: Xia Jiaqi , Bai Peng , Fan Weiliang , Li Qiming , Li Yongzheng , Wang Dehe , Yin Lei , Zhou Yu
Published: April 2021

T-cell recognition of somatic mutation-derived cancer neoepitopes can lead to tumor regression. Due to the difficulty to identify effective neoepitopes, constructing a database for sharing experimentally validated cancer neoantigens will be beneficial to precise cancer immunotherapy. Meanwhile, the routine neoepitope prediction in silico is important but laborious for clinical use. Here we present NEPdb, a database that contains more than 17,000 validated human immunogenic neoantigens and ineffective neoepitopes within human leukocyte antigens (HLAs) via curating published literature with our semi-automatic pipeline. Furthermore, NEPdb also provides pan-cancer level predicted HLA-I neoepitopes derived from 16,745 shared cancer somatic mutations, using state-of-the-art predictors. With a well-designed search engine and visualization modes, this database would enhance the efficiency of neoantigen-based cancer studies and treatments. NEPdb is freely available at http://nep.whu.edu.cn/.
The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy
Authors: Asiry Saeed , Kim Gina , Filippou Panagiota S. , Sanchez Luis Rivera , Entenberg David , Marks Douglas K. , Oktay Maja H. , Karagiannis George S.
Published: April 2021

Although cancer immunotherapy has resulted in unpreceded survival benefits to subsets of oncology patients, accumulating evidence from preclinical animal models suggests that the immunosuppressive tumor microenvironment remains a detrimental factor limiting benefit for many patient subgroups. Recent efforts on lymphocyte-mediated immunotherapies are primarily focused on eliminating cancer foci at primary and metastatic sites, but few studies have investigated the impact of these therapies on the highly complex process of cancer cell dissemination. The metastatic cascade involves the directional streaming of invasive/migratory tumor cells toward specialized blood vessel intravasation gateways, called TMEM doorways, to the peripheral circulation. Importantly, this process occurs under the auspices of a specialized tumor microenvironment, herewith referred to as “Dissemination Trajectory”, which is supported by an ample array of tumor-associated macrophages (TAMs), skewed towards an M2-like polarization spectrum, and which is also vital for providing microenvironmental cues for cancer cell invasion, migration and stemness. Based on pre-existing evidence from preclinical animal models, this article outlines the hypothesis that dissemination trajectories do not only support the metastatic cascade, but also embody immunosuppressive niches, capable of providing transient and localized immunosubversion cues to the migratory/invasive cancer cell subpopulation while in the act of departing from a primary tumor. So long as these dissemination trajectories function as “immune deserts”, the migratory tumor cell subpopulation remains efficient in evading immunological destruction and seeding metastatic sites, despite administration of cancer immunotherapy and/or other cytotoxic treatments. A deeper understanding of the molecular and cellular composition, as well as the signaling circuitries governing the function of these dissemination trajectories will further our overall understanding on TAM-mediated immunosuppression and will be paramount for the development of new therapeutic strategies for the advancement of optimal cancer chemotherapies, immunotherapies, and targeted therapies.
The Warburg Effect Occurs Rapidly in Stimulated Human Adult but Not Umbilical Cord Blood Derived Macrophages
Authors: Ó Maoldomhnaigh Cilian , Cox Donal J. , Phelan James J. , Malone Fergal D. , Keane Joseph , Basdeo Sharee A.
Published: April 2021

The Warburg effect, defined as increased glycolysis and decreased oxidative phosphorylation, occurs in murine macrophages following LPS stimulation and is required for activation. There are differences between human and murine macrophage metabolic responses to stimulation, with peak metabolite concentrations occurring earlier in humans than mice. Complex changes occur in the human immune system with age, resulting in the very young and the very old being more susceptible to infections. Anti-bacterial immune responses in umbilical cord immune cells are considered deficient but there is a paucity of data on the role that metabolism plays. We hypothesized that metabolic responses in human macrophages occur early during activation. In addition, we hypothesized that umbilical cord derived macrophages have an altered immunometabolic response compared with adult macrophages. We demonstrate that adult and cord blood monocyte derived macrophages (MDM) immediately increase glycolysis in response to stimulation with LPS or Mycobacterium tuberculosis (Mtb), however only adult MDM decrease oxidative phosphorylation. At 24 hours post stimulation, glycolysis remains elevated in both adult and cord blood MDM, oxidative phosphorylation remains unchanged in the cord blood MDM and has normalized in the adult MDM stimulated with Mtb. However, LPS stimulated adult MDM have increased oxidative phosphorylation at 24 hours, illustrating differences in metabolic responses to different stimuli, time-dependent variation in responses and differences in macrophage metabolism in adults compared with umbilical cord blood. We compared the phenotype and function of macrophages derived from adult or cord blood. Cord blood MDM secreted less TNF following Mtb stimulation and more IL-6 following LPS stimulation compared with adult MDM. Our findings demonstrate that whilst cord blood MDM exhibit an immediate increase in glycolytic flux in response to stimulation, similar to adult MDM, cord blood MDM do not concomitantly decrease oxygen consumption. This indicates that adult macrophages shift to Warburg metabolism immediately after stimulation, but cord blood macrophages do not. Understanding the differences in the metabolic profiles of macrophages over a human lifetime will enable the translation of immunometabolism into effective immuno-supportive therapies that could potentially be targeted at vulnerable populations, such as the very old and the very young.
Interplay of Opposing Effects of the WNT/β-Catenin Pathway and PPARγ and Implications for SARS-CoV2 Treatment
Authors: Vallée Alexandre , Lecarpentier Yves , Vallée Jean-Noël
Published: April 2021

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has quickly reached pandemic proportions. Cytokine profiles observed in COVID-19 patients have revealed increased levels of IL-1β, IL-2, IL-6, and TNF-α and increased NF-κB pathway activity. Recent evidence has shown that the upregulation of the WNT/β-catenin pathway is associated with inflammation, resulting in a cytokine storm in ARDS (acute respire distress syndrome) and especially in COVID-19 patients. Several studies have shown that the WNT/β-catenin pathway interacts with PPARγ in an opposing interplay in numerous diseases. Furthermore, recent studies have highlighted the interesting role of PPARγ agonists as modulators of inflammatory and immunomodulatory drugs through the targeting of the cytokine storm in COVID-19 patients. SARS-CoV2 infection presents a decrease in the angiotensin-converting enzyme 2 (ACE2) associated with the upregulation of the WNT/β-catenin pathway. SARS-Cov2 may invade human organs besides the lungs through the expression of ACE2. Evidence has highlighted the fact that PPARγ agonists can increase ACE2 expression, suggesting a possible role for PPARγ agonists in the treatment of COVID-19. This review therefore focuses on the opposing interplay between the canonical WNT/β-catenin pathway and PPARγ in SARS-CoV2 infection and the potential beneficial role of PPARγ agonists in this context.
T-Cell Receptor Therapy in the Treatment of Ovarian Cancer: A Mini Review
Authors: Wu Jessica W. Y. , Dand Sudiksha , Doig Lachlan , Papenfuss Anthony T. , Scott Clare L. , Ho Gwo , Ooi Joshua D.
Published: April 2021

Ovarian cancer, in particularly high-grade serous ovarian cancer (HGSOC) and ovarian carcinosarcoma (OCS), are highly aggressive and deadly female cancers with limited treatment options. These tumors are generally unresponsive to immune check-point inhibitor (ICI) therapy and are referred to as immunologically “cold” tumors. Cell-based therapy, in particular, adoptive T-cell therapy, is an alternative immunotherapy option that has shown great potential, especially chimeric antigen receptor T cell (CAR-T) therapy in the treatment of hematologic malignancies. However, the efficacy of CAR-T therapy in solid tumors has been modest. This review explores the potential of another cell-based therapy, T-cell receptor therapy (TCR-T) as an alternate treatment option for immunological “cold” OC and OCS tumors.
Tourist Knowledge, Pro-Conservation Intentions, and Tourist Concern for the Impacts of Whale-Watching in Las Perlas Archipelago, Panama
Authors: Cárdenas Susana , Gabela-Flores María Virginia , Amrein Arielle , Surrey Katie , Gerber Leah R. , Guzmán Hector M.
Published: April 2021

Whale watching has become an important economic activity for many coastal areas where whales aggregate at certain times of year. Las Perlas Archipelago in Panama is a breeding ground for humpback whales, where the numbers of both visitors and tour operators have increased in recent years with little compliance and enforcement of regulations. Nevertheless, there is potential to improve whale-watching management at this site and its use as a tool for education and conservation awareness. Our objective was to assess tourist knowledge, perceptions and pro-conservation attitudes related to whale watching and how this activity is managed in Las Perlas. One hundred and eleven tourists were surveyed in the summer of 2019 after they participated in whale−watching tours. Overall, respondents had little knowledge about whales and their conservation before a whale-watching trip. However, after the excursion, tourists felt they had learned more about whale biology and the regulations for whale-watching. Trip satisfaction after whale-watching activities was higher when whale behaviors, including breaching and tail slaps, were observed. Respondents expressed low satisfaction when there was an excessive number of boats around a whale-sighting. Concern for lack of compliance seemed to be associated with whale-watching operations that onboard tour guides. This study highlights the importance of whale watching as a tool for promoting whale conservation through education and the need to improve the enforcement of existing regulations and visitor monitoring to reduce potential negative impacts of whale-watching.
Influence of Non-protein Diets on Hepatic Metabolism and Endocrine in Barramundi (Lates calcarifer)
Authors: Fu Zhengyi , Zhou Shengjie , Yu Gang , Yang Rui , Han Mingyang , Ma Zhenhua
Published: April 2021

This study evaluated the effects of different dietary non-protein energy sources on hepatic metabolism and endocrine of barramundi. Fish were fed iso-energy diets (18 MJ kg–1) with two types of non-protein energy source in the experimental group and a regular diet was used as the control. The feeding trial lasted 56 days. In the present study, CPT1 and SCD expression in fish fed high lipid diet were upregulated and liver lipid metabolism was more active than the control group. Serum biochemical parameters including serum glucose, serum triacylglycerol and serum cholesterol were significantly increased. The IGF-I and IGF-II expressions were significantly upregulated, and growth performances were improved in fish fed the high lipid diet. When barramundi were fed with the high carbohydrate diet, GK expression was downregulated and cPEPCK expression was upregulated, indicating that glycogen might accumulate in liver. The fluctuation of serum biochemical parameters and the growth performance were not significantly different compared to the control group. In conclusion, high lipid diet can shorten the raising period, but it causes the change of metabolic level and the increase of useless adipose tissue; The high carbohydrate diet did not significantly improve the growth performance, and no significant metabolic abnormalities were observed, indicating that carbohydrate has the potential to be the feed energy supply source for juvenile barramundi. The results provide insights for further understanding the availability of non-protein energy sources in the diet of juvenile barramundi.
Case Report: Congenital Arthrogryposis and Unilateral Absences of Distal Arm in Congenital Zika Syndrome
Authors: Contreras-Capetillo Silvina Noemí , Palma-Baquedano José Rafael , Valadéz-González Nina , Manrique-Saide Pablo , Barrera-Pérez Hirian Alonso Moshe , Pinto-Escalante Doris , Pavía-Ruz Norma
Published: April 2021

Zika virus was recognized as a teratogen in 2015, when prenatal Zika infection was associated with neonatal microcephaly. The transmission, virulence, tropism, and consequences of Zika virus infection during pregnancy are currently studied. Decreased neural progenitor cells, arrest in neuronal migration and/or disruption of the maturation process of the fetus central nervous system have been associated. Congenital Zika Syndrome produces a fetal brain disruption sequence resulting in structural brain abnormalities, microcephaly, intracranial calcifications, fetal akinesia and arthrogryposis. Vascular abnormalities like unique umbilical artery and decreased cerebral vascular flow have been described in some patients. This article reports a Zika positive patient with sequence of fetal brain disruption, arthrogryposis and absence of distal third of the right forearm. This report expands the clinical observations of congenital Zika syndrome that may be related to disruptive vascular events.
Clinical Characteristics of Patients With Dizziness/Vertigo Accompanied by Posterior Semicircular Canal Hypofunction
Authors: Li Zheyuan , Liu Bo , Si Hongli , Li Kangzhi , Shen Bo , Li Xiang , Ling Xia , Yang Xu
Published: April 2021

Objective: To investigate the clinical characteristics of patients with dizziness/vertigo accompanied by loss of the posterior canal(s) (LPC).

Methods: Clinical data of 23 patients with LPC were collected. We determined video-head-impulse test (vHIT) gains of all six semicircular canals and correlated vHIT findings with other vestibulo-cochlear tests, including caloric test, ocular and cervical vestibular-evoked myogenic potentials (oVEMP, cVEMP), pure tone audiometry (PTA), and analyzed the differences in clinical manifestations of patients with LPC with different etiologies.

Results: LPC was identified in 23 patients. At the time of disease onset, most patients presented with dizziness (47.8%) and vertigo (30.4%) only, and some patients (21.7%) complained of unsteadiness. Among these 23 patients with LPC, there were 14 (60.9%) patients of isolated LPC (ILPC), 21 (91.3%) patients of unilateral LPC (ULPC), and 2 (8.7%) patients of bilateral LPC (BLPC). (1) Among 14 patients with ILPC, 13 (92.9%) patients had unilateral ILPC, the rate of ipsilesional impairment on caloric test, or oVEMP/cVEMP test or PTA ipsilesionally was 53.8% (7/13) in patients with unilateral ILPC. The causes of unilateral ILPC were vertigo/dizziness of unclear origin (38.5%), labyrinthine infarction (15.4%), vestibular migraine (15.4%), and other diseases (30.8%); (2) among 21 patients with ULPC, 7 patients (33.3%) were accompanied with horizontal semicircular canal hypofunction ipsilesionally, the abnormal rate of caloric test, or oVEMP/cVEMP tests or PTA ipsilesionally was 57.1%. The causes of ULPC were vertigo/dizziness of unclear origin (33.3%), autoimmune inner ear disease (14.3%), labyrinthine infarction (14.3%), vestibular neuritis (9.5%), vestibular migraine (9.5%), and other diseases (19.0%); (3) among two patients with BLPC, one patient presented with unsteadiness, the causes of BLPC were vestibular paroxysmia and autoimmune inner ear disease.

Conclusion: vHIT is a fast and effective method for assessing LPC, which can be used to detect isolated PC dysfunction. The causes of ILPC were peripheral origin or central origin. Patients with ILPC and ULPC mostly presented with dizziness/vertigo, and ULPC was often accompanied by ipsilateral vestibulo-cochlear impairment.
Systemic Administration of α7-Nicotinic Acetylcholine Receptor Ligands Does Not Improve Renal Injury or Behavior in Mice With Advanced Systemic Lupus Erythematosus
Authors: Morales Jessica Y. , Young-Stubbs Cassandra M. , Shimoura Caroline G. , Kem William R. , Uteshev Victor V. , Mathis Keisa W.
Published: April 2021

There is a critical need for safe treatment options to control inflammation in patients with systemic lupus erythematosus (SLE) since the inflammation contributes to morbidity and mortality in advanced disease. Endogenous neuroimmune mechanisms like the cholinergic anti-inflammatory pathway can be targeted to modulate inflammation, but the ability to manipulate such pathways and reduce inflammation and end organ damage has not been fully explored in SLE. Positive allosteric modulators (PAM) are pharmacological agents that inhibit desensitization of the nicotinic acetylcholine receptor (α7-nAChR), the main anti-inflammatory feature within the cholinergic anti-inflammatory pathway, and may augment α7-dependent cholinergic tone to generate therapeutic benefits in SLE. In the current study, we hypothesize that activating the cholinergic anti-inflammatory pathway at the level of the α7-nAChR with systemic administration of a partial agonist, GTS-21, and a PAM, PNU-120596, would reduce inflammation, eliminating the associated end organ damage in a mouse model of SLE with advanced disease. Further, we hypothesize that systemic α7 ligands will have central effects and improve behavioral deficits in SLE mice. Female control (NZW) and SLE mice (NZBWF1) were administered GTS-21 or PNU-120596 subcutaneously via minipumps for 2 weeks. We found that the increased plasma dsDNA autoantibodies, splenic and renal inflammation, renal injury and hypertension usually observed in SLE mice with advanced disease at 35 weeks of age were not altered by GTS-21 or PNU-120596. The anxiety-like behavior presented in SLE mice was also not improved by GTS-21 or PNU-120596. Although no significant beneficial effects of α7 ligands were observed in SLE mice at this advanced stage, we predict that targeting this receptor earlier in the pathogenesis of the disease may prove to be efficacious and should be addressed in future studies.
An Overview of Biological and Computational Methods for Designing Mechanism-Informed Anti-biofilm Agents
Authors: An Andy Y. , Choi Ka-Yee Grace , Baghela Arjun S. , Hancock Robert E. W.
Published: April 2021

Bacterial biofilms are complex and highly antibiotic-resistant aggregates of microbes that form on surfaces in the environment and body including medical devices. They are key contributors to the growing antibiotic resistance crisis and account for two-thirds of all infections. Thus, there is a critical need to develop anti-biofilm specific therapeutics. Here we discuss mechanisms of biofilm formation, current anti-biofilm agents, and strategies for developing, discovering, and testing new anti-biofilm agents. Biofilm formation involves many factors and is broadly regulated by the stringent response, quorum sensing, and c-di-GMP signaling, processes that have been targeted by anti-biofilm agents. Developing new anti-biofilm agents requires a comprehensive systems-level understanding of these mechanisms, as well as the discovery of new mechanisms. This can be accomplished through omics approaches such as transcriptomics, metabolomics, and proteomics, which can also be integrated to better understand biofilm biology. Guided by mechanistic understanding, in silico techniques such as virtual screening and machine learning can discover small molecules that can inhibit key biofilm regulators. To increase the likelihood that these candidate agents selected from in silico approaches are efficacious in humans, they must be tested in biologically relevant biofilm models. We discuss the benefits and drawbacks of in vitro and in vivo biofilm models and highlight organoids as a new biofilm model. This review offers a comprehensive guide of current and future biological and computational approaches of anti-biofilm therapeutic discovery for investigators to utilize to combat the antibiotic resistance crisis.
Gut Microbiota in Untreated Diffuse Large B Cell Lymphoma Patients
Authors: Yuan Li , Wang Wei , Zhang Wei , Zhang Yan , Wei Chong , Li Jingnan , Zhou Daobin
Published: April 2021

Intestinal microecology plays an important role in the development and progression of hematological malignancies. However, characteristics of gut microbiota in diffuse large B cell lymphoma (DLBCL) have not been reported. The microbiota composition of fecal samples from 25 untreated DLBCL patients and 26 healthy volunteers was examined by 16S rRNA gene sequencing. On α-diversity analysis, there was no significant difference in species diversity and abundance between the two groups. However, a significant difference was observed on β-diversity analysis. The intestinal microbiota in patients with DLBCL showed a continuous evolutionary relationship, which progressed from phylum, proteobacteria, to genus, Escherichia-Shigella. Their abundance was significantly higher than that of the control group. At the genus level, Allisonella, lachnospira, and Roseburia were more abundant in patients with DLBCL than in the control group. Functional prediction by PICRUSt indicated that thiamine metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis were significantly lower in the DLBCL group than in the control group. In conclusion, our results clearly demonstrate that the gut microbiota was changed significantly in DLBCL. The study highlights fundamental differences in the microbial diversity and composition of patients with DLBCL and paves the way for future prospective studies and microbiome-directed interventional trials to improve patient outcomes.
Sources and Assembly of Microbial Communities in Vineyards as a Functional Component of Winegrowing
Authors: Griggs Reid G. , Steenwerth Kerri L. , Mills David A. , Cantu Dario , Bokulich Nicholas A.
Published: April 2021

Microbiomes are integral to viticulture and winemaking – collectively termed winegrowing – where diverse fungi and bacteria can exert positive and negative effects on grape health and wine quality. Wine is a fermented natural product, and the vineyard serves as a key point of entry for quality-modulating microbiota, particularly in wine fermentations that are conducted without the addition of exogenous yeasts. Thus, the sources and persistence of wine-relevant microbiota in vineyards critically impact its quality. Site-specific variations in microbiota within and between vineyards may contribute to regional wine characteristics. This includes distinctions in microbiomes and microbiota at the strain level, which can contribute to wine flavor and aroma, supporting the role of microbes in the accepted notion of terroir as a biological phenomenon. Little is known about the factors driving microbial biodiversity within and between vineyards, or those that influence annual assembly of the fruit microbiome. Fruit is a seasonally ephemeral, yet annually recurrent product of vineyards, and as such, understanding the sources of microbiota in vineyards is critical to the assessment of whether or not microbial terroir persists with inter-annual stability, and is a key factor in regional wine character, as stable as the geographic distances between vineyards. This review examines the potential sources and vectors of microbiota within vineyards, general rules governing plant microbiome assembly, and how these factors combine to influence plant-microbe interactions relevant to winemaking.
A GC-MS/Single-Cell Method to Evaluate Membrane Transporter Substrate Specificity and Signaling
Authors: Fairweather Stephen J. , Okada Shoko , Gauthier-Coles Gregory , Javed Kiran , Bröer Angelika , Bröer Stefan
Published: April 2021

Amino acid transporters play a vital role in metabolism and nutrient signaling pathways. Typically, transport activity is investigated using single substrates and competing amounts of other amino acids. We used GC-MS and LC-MS for metabolic screening of Xenopus laevis oocytes expressing various human amino acid transporters incubated in complex media to establish their comprehensive substrate profiles. For most transporters, amino acid selectivity matched reported substrate profiles. However, we could not detect substantial accumulation of cationic amino acids by SNAT4 and ATB0,+ in contrast to previous reports. In addition, comparative substrate profiles of two related sodium neutral amino acid transporters known as SNAT1 and SNAT2, revealed the latter as a significant leucine accumulator. As a consequence, SNAT2, but not SNAT1, was shown to be an effective activator of the eukaryotic cellular growth regulator mTORC1. We propose, that metabolomic profiling of membrane transporters in Xenopus laevis oocytes can be used to test their substrate specificity and role in intracellular signaling pathways.
Salt-Dependent RNA Pseudoknot Stability: Effect of Spatial Confinement
Authors: Feng Chenjie , Tan Ya-Lan , Cheng Yu-Xuan , Shi Ya-Zhou , Tan Zhi-Jie
Published: April 2021

Macromolecules, such as RNAs, reside in crowded cell environments, which could strongly affect the folded structures and stability of RNAs. The emergence of RNA-driven phase separation in biology further stresses the potential functional roles of molecular crowding. In this work, we employed the coarse-grained model that was previously developed by us to predict 3D structures and stability of the mouse mammary tumor virus (MMTV) pseudoknot under different spatial confinements over a wide range of salt concentrations. The results show that spatial confinements can not only enhance the compactness and stability of MMTV pseudoknot structures but also weaken the dependence of the RNA structure compactness and stability on salt concentration. Based on our microscopic analyses, we found that the effect of spatial confinement on the salt-dependent RNA pseudoknot stability mainly comes through the spatial suppression of extended conformations, which are prevalent in the partially/fully unfolded states, especially at low ion concentrations. Furthermore, our comprehensive analyses revealed that the thermally unfolding pathway of the pseudoknot can be significantly modulated by spatial confinements, since the intermediate states with more extended conformations would loss favor when spatial confinements are introduced.
Reduced Retinal Microvascular Perfusion in Patients With Stroke Detected by Optical Coherence Tomography Angiography
Authors: Liu Baoyi , Hu Yijun , Ma Guixian , Xiao Yu , Zhang Bin , Liang Yingying , Zhong Pingting , Zeng Xiaomin , Lin Zhanjie , Kong Huiqian , Wu Guanrong , Du Zijing , Fang Ying , Huang Manqing , Wang Lijuan , Yang Xiaohong , Yu Honghua
Published: April 2021

Currently there is a shortage of biomarkers for stroke, one of the leading causes of death and disability in aging populations. Retinal vessels offer a unique and accessible “window” to study the microvasculature in vivo. However, the relationship between the retinal microvasculature and stroke is not entirely clear. To investigate the retinal microvascular characteristics in stroke, we recruited patients with stroke and age-matched control subjects from a tertiary hospital in China. The macular vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), foveal avascular zone (FAZ) metrics, and optical coherence tomography angiography (OCTA) measured optic disc VD were recorded for analysis. A total of 189 patients with stroke and 195 control subjects were included. After adjusting for sex, visual acuity, systolic and diastolic blood pressure, a history of smoking, levels of hemoglobulin (HbA1c), cholesterol, and high-density lipoprotein (HDL), the macular VD of SCP and DCP in all sectors was decreased in patients with stroke. In the stroke group, the VD around the FAZ and the VD of the optic disk were lower. Logistic regression found the parafovea-superior-hemi VD of DCP > 54.53% [odds ratio (OR): 0.169] as a protective factor of stroke. Using the integration of all OCTA parameters and traditional risk factors, the area under the receiver operating characteristic (AUC) curve of distinguishing patients with stroke was 0.962, with a sensitivity of 0.944 and a specificity of 0.871. Our study demonstrates that the retinal VD is decreased in patients with stroke independently of the traditional risk factors of stroke, which may shed light on the monitoring of stroke using the retinal microvascular parameters.