bluuebunny/crossref_metadata_2025 huggingface dataset:
Customized Borosilicate Bioglass Scaffolds With Excellent Biodegradation and Osteogenesis for Mandible Reconstruction
Authors: Zhang Peng , Yang Kang , Zhou Ziyu , Zhu Xingrong , Li Wenchao , Cao Chuanliang , Zhou Kui , Liao Lan , Ai Fanrong
Published: December 2020

Graft reconstruction of the mandible is an important approach that aims at improving the appearance and functionality of defected mandibles. The traditional implant materials are generally bioinert, non-degradable, and that they lack favorable pore structures for cell proliferation, which limit their clinical application. In this study, we used boron-containing bioactive glass which was combined with a three-dimensional (3D) printing technology to construct an osteoinductive implant scaffold, according to the imaging instructions of CT scan on bone defects. Here, the boron-containing bioglass scaffold (B-BGs) was prepared through sol-gel processing and a 3D print technique. Different boron content of borosilicate bioglass was prepared by incorporating B2O3 (molar: 19.4 and 38.8%) into 58S bioglass to replace parts of SiO2. For fabricated mandible implants through three-dimensional 3D printing of B-BGs (size: 8 × 2 mm; pore size: 250 μm) modified with borosilicate bioglass powder and sodium alginate. Notably, the compressive strength of the B-BGs was about 3.8 Mpa, which supported mandibular activity. Subsequently, the excellent biocompatibility of B-BGs was confirmed using cytotoxicity in vitro studies. Finally, data from in vivo experiments demonstrated that the B-BGs could promote bone regeneration and they could almost get completely degraded within 4 weeks. Our results showed that the boron-containing bioglass could repair mandibular defects.
Renewable Cyclopentanol From Catalytic Hydrogenation-Rearrangement of Biomass Furfural Over Ruthenium-Molybdenum Bimetallic Catalysts
Authors: Meng Shihang , Weng Yujing , Wang Xiaolong , Yin Hongxing , Wang Zhenfei , Sun Qi , Fan Maohong , Zhang Yulong
Published: December 2020

Biomass furfural-like compounds are chemicals that cannot be extracted from fossil materials, through which a large number of fine chemicals and fuel additives can be opened up, but one big efficiency problem during the transformation is the accumulation of oligomers. Here, we propose a novel and efficient Ru-Mo bimetallic catalyst for selective hydrogenation-rearrangement of furfural-like compounds. The result showed that an unprecedented rearrangement product selectivity of 89.1% to cyclopentanol was achieved under an optimized reaction condition over a 1%Ru−2.5%Mo/CNT catalyst reduced at 600°C. Subsequent characterization suggested that the catalyst presented with weak acidity and strong hydrogenation activity for the reaction, which not only ensures the smooth hydrogenation-rearrangement reaction but also inhibits the accumulation of furan polymers. These findings provide a convenient strategy to tune the catalytic performance of Mo-based catalysts by controlling the reduction and carburization conditions, which appear to be versatile for the rearrangement of furans and similar compounds.
Gonadal Sex Differentiation: Supporting Versus Steroidogenic Cell Lineage Specification in Mammals and Birds
Authors: Estermann Martin A. , Major Andrew T. , Smith Craig A.
Published: December 2020

The gonads of vertebrate embryos are unique among organs because they have a developmental choice; ovary or testis formation. Given the importance of proper gonad formation for sexual development and reproduction, considerable research has been conducted over the years to elucidate the genetic and cellular mechanisms of gonad formation and sexual differentiation. While the molecular trigger for gonadal sex differentiation into ovary of testis can vary among vertebrates, from egg temperature to sex-chromosome linked master genes, the downstream molecular pathways are largely conserved. The cell biology of gonadal formation and differentiation has long thought to also be conserved. However, recent discoveries point to divergent mechanisms of gonad formation, at least among birds and mammals. In this mini-review, we provide an overview of cell lineage allocation during gonadal sex differentiation in the mouse model, focusing on the key supporting and steroidogenic cells and drawing on recent insights provided by single cell RNA-sequencing. We compare this data with emerging information in the chicken model. We highlight surprising differences in cell lineage specification between species and identify gaps in our current understanding of the cell biology underlying gonadogenesis.
SARS-CoV-2 Infection in Asymptomatic Patients Hospitalized for Cardiac Emergencies: Implications for Patient Management
Authors: Kessler Thorsten , Wiebe Jens , Graf Tobias , Schunkert Heribert , Kastrati Adnan , Sager Hendrik B.
Published: December 2020

Background: The coronavirus disease (COVID-19) pandemic imposed diverse challenges on the health care system. Morbidity and mortality of non-COVID-19 emergencies might also have changed because hospitals may not be able to provide optimal care due to restructured resources and uncertainties how to deal with potentially infected patients. It has been recommended to stratify treatment of cardiovascular emergencies according to cardiovascular risk. However, data on the prevalence of asymptomatic SARS-CoV-2 infection in patients presenting with cardiac emergencies remain scarce.

Methods: We retrospectively analyzed patients' data from a tertiary cardiology department between April 15 and May 31, 2020. All patients were screened on admission for COVID-19 symptoms using a questionnaire and body temperature measurements. All hospitalized patients were routinely screened using nasopharyngeal swab testing.

Results: In total, we counted 710 urgent and emergency admissions. Nasopharyngeal swab tests were available in 689 (97%) patients, 409 and 280 of which presented as urgent and emergency admissions, respectively. Among 280 emergency admissions, none tested positive for SARS-CoV-2.

Conclusion: In cardiac emergency patients which were screened negative for COVID-19 symptoms, the prevalence of SARS-CoV-2 infection in regions with a modest overall prevalence is low. This finding might be helpful to better determine timing of emergency procedures and reasonable usage of protective equipment during the COVID-19 crisis and the future.
Machine Learning Revealed New Correlates of Chronic Pelvic Pain in Women
Authors: Elgendi Mohamed , Allaire Catherine , Williams Christina , Bedaiwy Mohamed A. , Yong Paul J.
Published: December 2020

Chronic pelvic pain affects one in seven women worldwide, and there is an urgent need to reduce its associated significant costs and to improve women's health. There are many correlated factors associated with chronic pelvic pain (CPP), and analyzing them simultaneously can be complex and involves many challenges. A newly developed interaction ensemble, referred to as INTENSE, was implemented to investigate this research gap. When applied, INTENSE aggregates three machine learning (ML) methods, which are unsupervised, as follows: interaction principal component analysis (IPCA), hierarchical cluster analysis (HCA), and centroid-based clustering (CBC). For our proposed research, we used INTENSE to uncover novel knowledge, which revealed new interactions in a sample of 656 patients among 25 factors: age, parity, ethnicity, body mass index, endometriosis, irritable bowel syndrome, painful bladder syndrome, pelvic floor tenderness, abdominal wall pain, depression score, anxiety score, Pain Catastrophizing Scale, family history of chronic pain, new or re-referral, age when first experienced pain, pain duration, surgery helpful for pain, infertility, smoking, alcohol use, trauma, dysmenorrhea, deep dyspareunia, CPP, and the Endometriosis Health Profile for functional quality of life. INTENSE indicates that CPP and the Endometriosis Health Profile are correlated with depression score, anxiety score, and the Pain Catastrophizing Scale. Other insights derived from these ML methods include the finding that higher body mass index was clustered with smoking and a history of life trauma. As well, sexual pain (deep dyspareunia) was found to be associated with musculoskeletal pain contributors (abdominal wall pain and pelvic floor tenderness). Therefore, INTENSE provided expert-like reasoning without training any model or prior knowledge of CPP. ML has the potential to identify novel relationships in the etiology of CPP, and thus can drive innovative future research.
The COVID-19 Diaries: Identity, Teaching, and Learning at a Crossroads
Authors: Sequeira Lavina , Dacey Charity M.
Published: December 2020

Despite the fact that American education has at its core strived to provide pathways of opportunity to remedy socio-economic inequalities, as educational institutions transitioned into online virtual classrooms due to the COVID-19 pandemic these inequalities have come into sharper focus for us. During the process of engaging in a larger self-study, we became more aware of the stark socio-economic disparities of our students in a virtual space, specifically amongst students of color, and how these disparities affected learning outcomes and their identity. Juxta positioning the situated in-between spaces of in-class and virtual environments our identities as educators were fluid and intersectional, negotiated in response to student interactions thereby enabling changes in our Dialogical Selves. The sample for this study consisted of 2 faculty members and 40 students. Data sources included reflexive journals, recorded class sessions, students' questionnaires, and artifacts such as student feedback collected through “exit tickets” as well as recorded meetings. Some findings include (1) students' identities were negotiated differently in face to face classrooms vs. virtual classrooms, (2) fluidity in intersectional identity due to intersections of I-positions in the dialogical self, and (3) acknowledging and accepting the presence of COVID-19 created a sense of community in the virtual classroom (4) incorporating self-care and caring pedagogical practices provided an empowering space for students and educators.
The Subhabitat Dependence of Biogeographic Pattern
Authors: Scrosati Ricardo A. , Freeman Matthew J. , Ellrich Julius A.
Published: December 2020

We introduce and test the subhabitat dependence hypothesis (SDH) in biogeography. This hypothesis posits that biogeographic pattern within a region differs when determined with species abundance data from different subhabitat types. It stems from the notion that the main abiotic factors that drive species distribution in different subhabitat types across a biogeographic region often vary differently across space. To test the SDH, we measured the abundance of algae and sessile invertebrates in two different subhabitats (high intertidal zone and mid-intertidal zone) at eight locations along the Atlantic Canadian coast. We conducted multivariate analyses of the species abundance data to compare alongshore biogeographic pattern between both zones. For both subhabitat types, location groupings based on community similarity not always responded to geographic proximity, leading to biogeographic patchiness to some extent. Nonetheless, both biogeographic patterns were statistically unrelated, thus supporting the SDH. This lack of concordance was most evident for southern locations, which clustered together based on high-intertidal data but showed considerable alongshore patchiness based on mid-intertidal data. We also found that the ordination pattern of these eight locations based on sea surface temperature data was significantly related to biogeographic pattern for the mid-intertidal zone but not for the high intertidal zone. This finding supports the rationale behind the SDH due to the longer periods of submergence experienced by the mid-intertidal zone. Overall, we conclude that biogeographic pattern within a region can depend on the surveyed subhabitat type. Thus, biological surveys restricted to specific subhabitats may not properly reveal biogeographic pattern for a biota as a whole or even just for other subhabitats. As many studies generate biogeographic information with data only for specific subhabitats, we recommend testing the SDH in other systems to determine its domain of application.
Quantification of Bacterial Colonization in Dental Hard Tissues Using Optimized Molecular Biological Methods
Authors: Sterzenbach Torsten , Pioch Anne , Dannemann Martin , Hannig Christian , Weber Marie-Theres
Published: December 2020

Bacterial infections of root canals and the surrounding dental hard tissue are still a challenge due to biofilm formation as well as the complex root canal anatomy. However, current methods for analyzing biofilm formation, bacterial colonization of root canals and dental hard tissue [e.g., scanning electron microscopy, confocal laser scanning microscopy (CLSM) or determination of colony forming units (CFU)] are time-consuming and only offer a selective qualitative or semi-quantitative analysis. The aim of the present study is the establishment of optimized molecular biological methods for DNA-isolation and quantification of bacterial colonization via quantitative PCR (qPCR) from dental hard tissue. Root canals of human premolars were colonized with Enterococcus faecalis. For isolation of DNA, teeth were then grinded with a cryo mill. Since the hard tissues dentin and especially enamel belong to the hardest materials in the human organism, the isolation of bacterial DNA from root dentin is very challenging. Therefore, treatment steps for the isolation of DNA from grinded teeth were systematically analyzed to allow improved recovery of bacterial DNA from dental hard tissues. Starting with the disintegration of the peptidoglycan-layer of bacterial cells, different lysozyme solutions were tested for efficacy. Furthermore, incubation times and concentrations of chelating agents such as EDTA were optimized. These solutions are crucial for the disintegration of teeth and hence improve the accessibility of bacterial DNA. The final step was the determination of prior bacterial colonization of each root canal as determined by qPCR and comparing the results to alternative methods such as CFU. As a result of this study, optimized procedures for bacterial DNA-isolation from teeth were established, which result in an increased recovery rate of bacterial DNA. This method allows a non-selective and straightforward procedure to quantify bacterial colonization from dental hard tissue. It can be easily adapted for other study types such as microbiome studies and for comparable tissues like bones.
Sharing CD4+ T Cell Loss: When COVID-19 and HIV Collide on Immune System
Authors: Peng Xiaorong , Ouyang Jing , Isnard Stéphane , Lin John , Fombuena Brandon , Zhu Biao , Routy Jean-Pierre
Published: December 2020

COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis. Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outcome. As CD4+ T cells play a critical role in orchestrating responses against viral infections, important lessons can be drawn by comparing T cell response in COVID-19 and in HIV infection and by studying HIV-infected patients who became infected by SARS-CoV-2. We critically reviewed host characteristics and hyper-inflammatory response in these two viral infections to have a better insight on the large difference in clinical outcome in persons being infected by SARS-CoV-2. The better understanding of mechanism of T cell dysfunction will contribute to the development of targeted therapy against severe COVID-19 and will help to rationally design vaccine involving T cell response for the long-term control of viral infection.
Specific Induction of Double Negative B Cells During Protective and Pathogenic Immune Responses
Authors: Ruschil Christoph , Gabernet Gisela , Lepennetier Gildas , Heumos Simon , Kaminski Miriam , Hracsko Zsuzsanna , Irmler Martin , Beckers Johannes , Ziemann Ulf , Nahnsen Sven , Owens Gregory P. , Bennett Jeffrey L. , Hemmer Bernhard , Kowarik Markus C.
Published: December 2020

Double negative (DN) (CD19+CD20lowCD27-IgD-) B cells are expanded in patients with autoimmune and infectious diseases; however their role in the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood B cell subsets, we observed an inflated DN B cell population in patients with variety of active inflammatory conditions: myasthenia gravis, Guillain-Barré syndrome, neuromyelitis optica spectrum disorder, meningitis/encephalitis, and rheumatic disorders. Furthermore, we were able to induce DN B cells in healthy subjects following vaccination against influenza and tick borne encephalitis virus. Transcriptome analysis revealed a gene expression profile in DN B cells that clustered with naïve B cells, memory B cells, and plasmablasts. Immunoglobulin VH transcriptome sequencing and analysis of recombinant antibodies revealed clonal expansion of DN B cells that were targeted against the vaccine antigen. Our study suggests that DN B cells are expanded in multiple inflammatory neurologic diseases and represent an inducible B cell population that responds to antigenic stimulation, possibly through an extra-follicular maturation pathway.
Effects of Ocean Acidification on Coral Endolithic Bacterial Communities in Isopora palifera and Porites lobata
Authors: Yang Sung-Yin , Lu Chih-Ying , Tang Sen-Lin , Das Rocktim Ramen , Sakai Kazuhiko , Yamashiro Hideyuki , Yang Shan-Hua
Published: December 2020

Endolithic microbes in coral reefs may act as a nutrient source for their coral hosts. Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), which may affect marine organisms and ecosystems, especially calcifying organisms such as reef-building corals. However, knowledge of how OA affects marine microbes remains limited, and little research has been done on how coral endolithic communities respond to shifting environmental baselines. In this study, the endolithic communities of two common shallow water coral species, Isopora palifera and Porites lobata, were examined to investigate the microbial community dynamics under OA treatments. The colonies were placed in an environment with a partial pressure of carbon dioxide (pCO2) of 1,000 or 400 ppm (control) for 2 months. Several I. palifera colonies bleached and died at 1,000 ppm pCO2, but the P. lobata colonies remained unaffected. Inversely, the endolithic community in P. lobata skeletons showed significant changes after OA treatment, whereas no significant dynamics were observed among the I. palifera endoliths. Our findings suggest that the skeletal structures of different coral species may play a key role in corals host and endoliths under future high-OA scenarios.
Macrophage Markers Do Not Add to the Prediction of Liver Fibrosis by Transient Elastography in Patients With Metabolic Associated Fatty Liver Disease
Authors: Kazankov Konstantin , Rosso Chiara , Younes Ramy , Armandi Angelo , Hagström Hannes , Møller Holger Jon , Stål Per , Bugianesi Elisabetta , Grønbæk Henning
Published: December 2020

Background and Aims: Non-invasive fibrosis staging is essential in metabolic associated fatty liver disease (MAFLD). Transient elastography (TE) is a well-established method for liver fibrosis assessment. We have previously shown that the macrophage marker sCD163 is an independent predictor for fibrosis in MAFLD. In the present study we tested whether the combination of macrophage markers and TE improves fibrosis prediction.

Methods: We measured macrophage markers soluble (s)CD163 and mannose receptor (sMR) in two independent cohorts from Italy (n = 141) and Sweden (n = 70) with biopsy-proven MAFLD and available TE.

Results: In the Italian cohort, TE and sCD163 showed similar moderate associations with liver fibrosis (rho = 0.56, p < 0.001 and rho = 0.42, p < 0.001, respectively). TE had an area under the Receiver Operating Characteristics curve (AUROC, with 95% CI) for fibrosis; F ≥ 2 = 0.79 (0.72–0.86), F ≥ 3 = 0.81 (0.73–0.89), F4 = 0.95 (0.90–1.0). sCD163 also predicted fibrosis well [F ≥ 2 = 0.71 (0.63–0.80), F ≥ 3 = 0.82 (0.74–0.90), F4 = 0.89 (0.76–1.0)]. However, combining sCD163 and TE did not improve the AUROCs significantly [F ≥ 2 = 0.79 (0.72–0.86), F ≥ 3 = 0.85 (0.78–0.92), F4 = 0.97 (0.93–1.0)]. In the Swedish cohort, TE showed a closer association with fibrosis (rho = 0.73, p < 0.001) than sCD163 (rho = 0.43, p < 0.001) and sMR (rho = 0.46, p < 0.001). TE predicted fibrosis well [F ≥ 2 = 0.88 (0.80–0.97), F ≥ 3 = 0.90 (0.83–0.97), F4 = 0.87 (0.78–0.96)], whereas sCD163 did not (best AUROC 0.75). sMR showed a better prediction [F ≥ 2 = 0.68 (0.56–0.81), F ≥ 3 = 0.82 (0.71–0.92), F4 = 0.79 (0.66–0.93)], but the addition of sMR did not further improve the prediction of fibrosis by TE.

Conclusion: In these cohorts of MAFLD patients, TE was superior to macrophage markers for fibrosis prediction and in contrast to our hypothesis the addition of these markers to TE did not improve its predictive capability.
The Total and Active Bacterial Community of the Chlorolichen Cetraria islandica and Its Response to Long-Term Warming in Sub-Arctic Tundra
Authors: Klarenberg Ingeborg J. , Keuschnig Christoph , Warshan Denis , Jónsdóttir Ingibjörg Svala , Vilhelmsson Oddur
Published: December 2020

Lichens are traditionally defined as a symbiosis between a fungus and a green alga and or a cyanobacterium. This idea has been challenged by the discovery of bacterial communities inhabiting the lichen thalli. These bacteria are thought to contribute to the survival of lichens under extreme and changing environmental conditions. How these changing environmental conditions affect the lichen-associated bacterial community composition remains unclear. We describe the total (rDNA-based) and potentially metabolically active (rRNA-based) bacterial community of the lichen Cetaria islandica and its response to long-term warming using a 20-year warming experiment in an Icelandic sub-Arctic tundra. 16S rRNA and rDNA amplicon sequencing showed that the orders Acetobacterales (of the class Alphaproteobacteria) and Acidobacteriales (of the phylum Acidobacteria) dominated the bacterial community. Numerous amplicon sequence variants (ASVs) could only be detected in the potentially active community but not in the total community. Long-term warming led to increases in relative abundance of bacterial taxa on class, order and ASV level. Warming altered the relative abundance of ASVs of the most common bacterial genera, such as Granulicella and Endobacter. The potentially metabolically active bacterial community was also more responsive to warming than the total community. Our results suggest that the bacterial community of the lichen C. islandica is dominated by acidophilic taxa and harbors disproportionally active rare taxa. We also show for the first time that climate warming can lead to shifts in lichen-associated bacterial community composition.
Identification of Potential Inhibitors of 3CL Protease of SARS-CoV-2 From ZINC Database by Molecular Docking-Based Virtual Screening
Authors: Abdusalam Ashraf Ahmed Ali , Murugaiyah Vikneswaran
Published: December 2020

The rapid outbreak of Coronavirus Disease 2019 (COVID-19) that was first identified in Wuhan, China is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The 3CL protease (3CLpro) is the main protease of the SARS-CoV-2, which is responsible for the viral replication and therefore considered as an attractive drug target since to date there is no specific and effective vaccine available against this virus. In this paper, we reported molecular docking-based virtual screening (VS) of 2000 compounds obtained from the ZINC database and 10 FDA-approved (antiviral and anti-malaria) on 3CLpro using AutoDock Vina to find potential inhibitors. The screening results showed that the top four compounds, namely ZINC32960814, ZINC12006217, ZINC03231196, and ZINC33173588 exhibited high affinity at the 3CLpro binding pocket. Their free energy of binding (FEB) were −12.3, −11.9, −11.7, and −11.2 kcal/mol while AutoDock Vina scores were −12.61, −12.32, −12.01, and -11.92 kcal/mol, respectively. These results were better than the co-crystallized ligand N3, whereby its FEB was −7.5 kcal/mol and FDA-approved drugs. Different but stable interactions were obtained between the four identified compounds with the catalytic dyad residues of the 3CLpro. In conclusion, novel 3CLpro inhibitors from the ZINC database were successfully identified using VS and molecular docking approach, fulfilling the Lipinski rule of five, and having low FEB and functional molecular interactions with the target protein. The findings suggests that the identified compounds may serve as potential leads that act as COVID-19 3CLpro inhibitors, worthy for further evaluation and development.
Endovascular Treatment of Tiny Aneurysms With Low-Profile Visualized Intraluminal Support Devices Using a “Compressed” Stent Technique
Authors: Zhou Yangyang , Peng Qichen , Wu Xinzhi , Zhang Yisen , Liu Jian , Yang Xinjian , Mu Shiqing
Published: December 2020

Objective: To investigate the safety and efficacy of low-profile visualized intraluminal support (LVIS) stent-assisted coiling of intracranial tiny aneurysms using a “compressed” stent technique.

Methods: We retrospectively analyzed patients with tiny aneurysms treated in our hospital with LVIS devices using a compressed stent technique. We analyzed patients' imaging outcomes, clinical outcomes, and complications.

Results: Forty-two tiny aneurysms in 42 patients were included in this study cohort; 8 patients presented with subarachnoid hemorrhage at admission. The immediate postoperative complete embolization rate was 76.2% (32/42). After an average of 8.5 months of imaging follow-up, the complete embolization rate was 90.5% (38/42), and no aneurysm recanalization occurred. After an average of 24.4 months of clinical follow-up, 95.2% (40/42) of the patients achieved favorable clinical outcomes (modified Rankin scale = 0/1). Operation-related complications occurred in two patients (4.8%); one intraoperative acute thrombosis, and one significant unilateral decreased vision during the postoperative follow-up.

Conclusion: LVIS stent-assisted coiling of intracranial tiny aneurysms using a compressed stent technique is safe and effective. Combined stent compression technology is beneficial to maximize the complete embolization of aneurysms and reduce aneurysm recanalization. This study expands the clinical applicability of LVIS stents.
Responses of Neurons in the Medullary Lateral Tegmental Field and Nucleus Tractus Solitarius to Vestibular Stimuli in Conscious Felines
Authors: Bielanin John P. , Douglas Nerone O. , Shulgach Jonathan A. , McCall Andrew A. , Miller Derek M. , Amin Pooja R. , Murphey Charles P. , Barman Susan M. , Yates Bill J.
Published: December 2020

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.
N2b Reflects the Cognitive Changes in Executive Functioning After Concussion: A Scoping Review
Authors: Krokhine Sophie N. , Ewers Nathalee P. , Mangold Kiersten I. , Boshra Rober , Lin Chia-Yu A. , Connolly John F.
Published: December 2020

Objectives: The N2b is an event-related potential (ERP) component thought to index higher-order executive function. While the impact of concussion on executive functioning is frequently discussed in the literature, limited research has been done on the role of N2b in evaluating executive functioning in patients with concussion. The aims of this review are to consolidate an understanding of the cognitive functions reflected by the N2b and to account for discrepancies in literature findings regarding the N2b and concussion.

Methods: A scoping review was conducted on studies that used the N2b to measure cognitive functioning in healthy control populations, as well as in people with concussions.

Results: Sixty-six articles that met inclusion criteria demonstrated that the N2b effectively represents stimulus-response conflict management, response selection, and response inhibition. However, the 19 included articles investigating head injury (using terms such as concussion, mild head injury, and mild traumatic brain injury) found widely varied results: some studies found the amplitude of the N2b to be increased in the concussion group, while others found it to be decreased or unchanged.

Conclusion: Based on the available evidence, differences in the amplitude of the N2b have been linked to response selection, conflict, and inhibition deficits in concussion. However, due to large variations in methodology across studies, findings about the directionality of this effect remain inconclusive. The results of this review suggest that future research should be conducted with greater standardization and consistency.
The Effect of Bilingualism on Cue-Based vs. Memory-Based Task Switching in Older Adults
Authors: Rieker Jennifer A. , Reales José Manuel , Ballesteros Soledad
Published: December 2020

Findings suggest a positive impact of bilingualism on cognition, including the later onset of dementia. However, it is not clear to what extent these effects are influenced by variations in attentional control demands in response to specific task requirements. In this study, 20 bilingual and 20 monolingual older adults performed a task-switching task under explicit task-cuing vs. memory-based switching conditions. In the cued condition, task switches occurred in random order and a visual cue signaled the next task to be performed. In the memory-based condition, the task alternated after every second trial in a predictable sequence without presenting a cue. The performance of bilinguals did not vary across experimental conditions, whereas monolinguals experienced a pronounced increase in response latencies and error rates in the cued condition. Both groups produced similar switch costs (difference in performance on switch trials as opposed to repeating trials within the mixed-task block) and mixing costs (difference in performance on repeat trials of a mixed-task block as opposed to trials of a single-task block), but bilinguals produced them with lower response latencies. The cognitive benefits of bilingualism seem not to apply to executive functions per se but to affect specific cognitive processes that involve task-relevant context processing. The present results suggest that lifelong bilingualism could promote in older adults a flexible adjustment to environmental cues, but only with increased task demands. However, due to the small sample size, the results should be interpreted with caution.
Peripheral Levels of Renin-Angiotensin System Components Are Associated With Cognitive Performance in Huntington’s Disease
Authors: Rocha Natalia P. , Cleary Courtney , Colpo Gabriela D. , Furr Stimming Erin , Teixeira Antonio L.
Published: December 2020

The renin-angiotensin system (RAS) has proven to be involved in the pathophysiology of neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), serving as a potential therapeutic target and a disease burden marker. Studies have associated negative clinical outcomes with the activation of the classical RAS arm composed of the angiotensin-converting enzyme (ACE) and angiotensin (Ang) II, while suggested positive outcomes with the activation of the counter-regulatory RAS arm involving ACE2 and Ang-(1–7). Huntington’s disease (HD) shares many pathological and clinical outcomes with AD and PD, but the evidence of direct involvement of RAS components in the pathophysiology of HD is still limited and needs further investigation. Herein, we investigated peripheral levels of the RAS components Ang II, Ang-(1–7), ACE, and ACE2 in controls, premanifest, and manifest HD gene carriers and their relationship with clinical outcomes. Peripheral blood samples were collected via phlebotomy, and plasma concentrations of RAS components were measured by Enzyme-Linked Immunosorbent Assay. Clinical evaluation included a questionnaire about socio-demographic characteristics, motor, and cognitive assessments. Results showed (1) no significant group differences in plasma concentrations of RAS components; (2) positive correlations between ACE2 and Verbal Fluency Test (VFT) scores; and (3) negative correlations between Ang II and Mini–Mental State Examination scores. These results corroborate the proposed balance between the classical (ACE/Ang II) and the counter-regulatory [ACE2/Ang-(1–7)] arms of the RAS, with the former associated with negative clinical outcomes and the latter with positive effects in HD.
Degeneration-Dependent Retinal Remodeling: Looking for the Molecular Trigger
Authors: Telias Michael , Nawy Scott , Kramer Richard H.
Published: December 2020

Vision impairment and blindness in humans are most frequently caused by the degeneration and loss of photoreceptor cells in the outer retina, as is the case for age-related macular degeneration, retinitis pigmentosa, retinal detachment and many other diseases. While inner retinal neurons survive degeneration, they undergo fundamental pathophysiological changes, collectively known as “remodeling.” Inner retinal remodeling downstream to photoreceptor death occurs across mammalian retinas from mice to humans, independently of the cause of degeneration. It results in pervasive spontaneous hyperactivity and membrane hyperpermeability in retinal ganglion cells, which funnel all retinal signals to the brain. Remodeling reduces light detection in vision-impaired patients and precludes meaningful vision restoration in blind individuals. In this review, we summarize current hypotheses proposed to explain remodeling and their potential medical significance highlighting the important role played by retinoic acid and its receptor.
Prognostic and Predictive Value of the American Joint Committee on Cancer Pathological Prognostic Staging System in Nodal Micrometastatic Breast Cancer
Authors: Shi Jian , Lian Chen-Lu , Chi Feng , Zhou Ping , Lei Jian , Hua Li , Wang Jun , He Zhen-Yu , Wu San-Gang
Published: December 2020

Introduction

To investigate the prognostic and predictive effect of the American Joint Committee on Cancer (AJCC) 8th edition pathological prognostic staging system in patients with T1-2N1micM0 breast cancer who underwent mastectomy.

Methods

Data from T1-2N1micM0 breast cancer patients who underwent mastectomy from 2010–2014 were obtained from the Surveillance, Epidemiology, and End Results program. The chi-square test, binomial logistics regression, receiver-operating characteristics curve, competing-risk regression model, Cox proportional hazards regression model, and proportional hazard assumption were used for statistical analyses.

Results

We identified 4,729 patients, including 1,062 patients were received postmastectomy radiotherapy (PMRT). Stage change occurred in 88.2% of the patients, of which 84.4% were downstaged and 3.7% were upstaged. Patients with higher pathological prognostic stages were independently predicted to receive PMRT. The 5-year breast cancer-specific survival (BCSS) was 97.5, 93.7, 90.1, 86.0, and 73.5% in disease stages IA, IB, IIA, IIB, and IIIA, respectively, according to the 8th edition criteria (P < 0.001). The AJCC 8th edition demonstrated moderate discriminative ability, and it had a significantly better ability to predict the BCSS than the AJCC 7th edition criteria (P < 0.001). The multivariate prognostic analysis showed that the new pathological prognostic staging was an independent prognostic factor affecting the BCSS. The BCSS worsened with an increase in the stage. The PMRT did not affect the BCSS regardless of the pathological prognostic stage. Similar trends were found using the competing-risks regression model.

Conclusions

The 8th AJCC breast cancer pathological prognostic staging system downstaged 84.4% of patients with T1-2N1micM0 disease and the survival outcome prediction with this staging system was more accurate than the AJCC 7th edition system. Our study does not support using the prognostic stage as a guideline to escalate of PMRT.
Radiotherapy Plus Chemotherapy Is Associated With Improved Survival Compared to Radiotherapy Alone in Patients With Primary Vaginal Carcinoma: A Retrospective SEER Study
Authors: Zhou Wei-li , Yue Yang-yang
Published: December 2020

Background

The efficacy of radiotherapy plus chemotherapy (RTCT) versus radiotherapy alone (RT) in the treatment of primary vaginal carcinoma has been controversial. We aimed to evaluate the up-to-date efficacy of RTCT on primary vaginal carcinoma in a real-world cohort.

Methods

We performed a retrospective analysis in patients with primary vaginal carcinoma retrieved from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2016. Kaplan–Meier survival curves were plotted and compared by the log-rank test. Inverse probability weighting (IPW)-adjusted multivariate Cox proportional hazards and Fine-Gray competing-risk model was applied.

Results

Of the 1,813 qualified patients with primary vaginal carcinoma from 2004 to 2016, 1,137 underwent RTCT and 676 underwent RT. The median survival time was 34 months for the RT group and 63 months for the RTCT group. RTCT was significantly associated with improved overall survival (unadjusted HR = 0.71, 95% CI 0.62–0.82, p < 0.001; adjusted HR = 0.73, 95% CI 0.63–0.84, p < 0.001) and cancer-specific survival (unadjusted sHR = 0.81, 95% CI 0.69–0.95, p = 0.012; adjusted sHR = 0.81, 95% CI 0.69–0.96, p = 0.016). Age, histological type, tumor size, surgery, and FIGO stage were all independent prognostic factors for survival (p < 0.05 for all). Subgroup analysis demonstrated that RTCT was significantly associated with better survival in most subgroups, except for those with adenocarcinoma, tumor size <2 cm, or FIGO stage I. Moreover, sensitivity analysis did not alter the beneficial effects of RTCT.

Conclusion

RTCT is significantly correlated with prolonged survival in patients with primary vaginal carcinoma. RTCT should be applied to most patients with primary vaginal carcinoma instead of RT alone, except for those with adenocarcinoma, tumor size <2 cm, or FIGO stage I.
Radiomics Approach for Prediction of Recurrence in Non-Functioning Pituitary Macroadenomas
Authors: Zhang Yang , Ko Ching-Chung , Chen Jeon-Hor , Chang Kai-Ting , Chen Tai-Yuan , Lim Sher-Wei , Tsui Yu-Kun , Su Min-Ying
Published: December 2020

Objectives

A subset of non-functioning pituitary macroadenomas (NFPAs) may exhibit early progression/recurrence (P/R) after surgical resection. The purpose of this study was to apply radiomics in predicting P/R in NFPAs.

Methods

Only patients who had undergone preoperative MRI and postoperative MRI follow-ups for more than 1 year were included in this study. From September 2010 to December 2017, 50 eligible patients diagnosed with pathologically confirmed NFPAs were identified. Preoperative coronal T2WI and contrast-enhanced (CE) T1WI imaging were analyzed by computer algorithms. For each imaging sequence, 32 first-order features and 75 texture features were extracted. Support vector machine (SVM) classifier was utilized to evaluate the importance of extracted parameters, and the most significant three parameters were used to build the prediction model. The SVM score was calculated based on the three selected features.

Results

Twenty-eight patients exhibited P/R (28/50, 56%) after surgery. The median follow-up time was 38 months, and the median time to P/R was 20 months. Visual disturbance, hypopituitarism, extrasellar extension, compression of the third ventricle, large tumor height and volume, failed optic chiasmatic decompression, and high SVM score were more frequently encountered in the P/R group (p < 0.05). In multivariate Cox hazards analysis, symptoms of sex hormones, hypopituitarism, and SVM score were high risk factors for P/R (p < 0.05) with hazard ratios of 10.71, 2.68, and 6.88. The three selected radiomics features were T1 surface-to-volume radio, T1 GLCM-informational measure of correlation, and T2 NGTDM-coarseness. The radiomics predictive model shows 25 true positive, 16 true negative, 6 false positive, and 3 false negative cases, with an accuracy of 82% and AUC of 0.78 in differentiating P/R from non-P/R NFPAs. For SVM score, optimal cut-off value of 0.537 and AUC of 0.87 were obtained for differentiation of P/R. Higher SVM scores were associated with shorter progression-free survival (p < 0.001).

Conclusions

Our preliminary results showed that objective and quantitative MR radiomic features can be extracted from NFPAs. Pending more studies and evidence to support the findings, radiomics analysis of preoperative MRI may have the potential to offer valuable information in treatment planning for NFPAs.
Post-infectious Bronchiolitis Obliterans: HRCT, DECT, Pulmonary Scintigraphy Images, and Clinical Follow-up in Eight Children
Authors: Chen I-Chen , Hsu Jui-Sheng , Chen Yu-Wen , Liu Yi-Ching , Wu Yen-Hsien , Hsu Jong-Hau , Cheng Yi-Fang , Dai Zen-Kong
Published: December 2020

Background:Bronchiolitis obliterans (BO), first mentioned in 1901, is a severe and rare chronic lung disease in children. BO has various etiologies and the most common in children is post-infectious BO (PIBO). High resolution CT (HRCT) is an often-used image tool for the diagnosis of BO, and pulmonary scintigraphy is an alternative tool that can functionally evaluate BO. Recently, dual-energy computed tomography (DECT) have also been applied to BO for its accuracy and safety. Here we described the characteristics of HRCT, pulmonary scintigraphy, DECT, and the clinical profiles of patients with PIBO.

Methods:This is a retrospective and descriptive study. Data were collected from patients diagnosed with PIBO from 2014 to 2019 in the Pediatric Cardiopulmonary Outpatient Clinics of Kaohsiung Medical University Hospital. The diagnosis was based on clinical, chest X-ray, and HRCT findings. Clinical profile, radiological characteristics, and images of pulmonary scintigraphy were documented.

Results:Eight children (4 boys and 4 girls) were diagnosed with PIBO at a mean age of 25.8 months (range 15 to 41 months). Two of our patients developed pulmonary hypertension. The most common HRCT finding is mosaic pattern, where match ventilation/perfusion (V/Q) defects is a general feature in pulmonary scintigraphy. DECT pulmonary blood vasculature images revealed various degrees of decreased perfusion and is compatible with the decreased perfusion on pulmonary scintigraphy.

Conclusion:The therapeutic strategy of PIBO is still lacking of standardization. HRCT and V/Q scans are important image tools in diagnosis and follow-up of BO. DECT may be used in BO patients as it has no additional radiation exposure and add value on functional information of HRCT.
Systematic Review: Study of the Prescribing Pattern of Antibiotics in Outpatients and Emergency Departments in the Gulf Region
Authors: Mahmood Rana Kamran , Gillani Syed Wasif , Saeed Muhammad Waqas , Hafeez Muhammad Umar , Gulam Shabaz Muhammad
Published: December 2020

Purpose: To study the prescribing pattern of antibiotics in outpatients and emergency departments in the Gulf region. To compare the appropriateness of prescriptions and antibiotics commonly prescribed for respiratory tract infection.

Method: The search was limited to the years 2008–2020, and articles had to be in English. Articles were searched from various resources and evaluated using PRISMA. Forty-one articles were selected and screened, and in the end, 17 articles were included in the study. All articles were selected from the gulf region of six countries: UAE, Saudi Arabia, Qatar, Oman, Yemen, and Bahrain. Only primary literature were included. Inpatient and literature from other countries outside the gulf region were excluded.

Result: Penicillins, cephalosporins, and macrolides are highly useful antibiotics for respiratory tract infections. Ceftriaxone IV is recommended in acute respiratory tract infection if therapy with penicillin fails. Most of the antibiotic prescriptions in Gulf countries are inappropriate. Inappropriate antibiotic prescribing in the gulf region varies from place to place and reaches a maximum of 80%. Antibiotics may be prescribed with the wrong dosage or frequency and inappropriate guidelines. Penicillins are prescribed at about 50–60%; the most common penicillins prescribed are amoxicillin and co-amoxiclave. Cephalosporins are prescribed at about 30%, and the most common are third-generation. Macrolides are prescribed at about 17–20%, and the most common macrolides are azithromycin and clarithromycin. Fluoroquinolones are prescribed at about 10–12%, of which levofloxacin and ciprofloxacin are more commonly prescribed with metronidazole at 10%.

Conclusion: It is suggested that the antibiotic-prescribing pattern in outpatient and emergency departments in the Gulf region are highly inappropriate and need improvement through education, following guidelines, annual vaccination, and stewardship programs; the most prescribed antibiotic is amoxicillin/co-amoxiclave, and the most often encountered infection in outpatients is acute respiratory tract infection.
Novel Strategies for Endothelial Preservation in Lung Transplant Ischemia-Reperfusion Injury
Authors: Jungraithmayr Wolfgang
Published: December 2020

Lung ischemia reperfusion (IR) injury inevitably occurs during lung transplantation. The pulmonary endothelium is the primary target of IR injury that potentially results in severe pulmonary dysfunction. Over the last decades, various molecules, receptors, and signaling pathways were identified in order to develop treatment strategies for the preservation of the pulmonary endothelium against IR injury. We here review the latest and most promising therapeutic strategies for the protection of the endothelium against IR injury. These include the stabilization of the endothelial glycocalyx, inhibition of endothelial autophagy, inhibition of adhesion molecules, targeting of angiotensin-converting enzyme, and traditional viral and novel non-viral gene transfer approaches. Though some of these strategies proved to be promising in experimental studies, very few of these treatment concepts made the transfer into clinical application. This dilemma underscores the need for more experimental evidence for the translation into clinical studies to invent therapeutic concepts against IR injury-mediated endothelial damage.