bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonal Evolution During Stress Hematopoiesis
Authors: Link Daniel C.
Published: April 2021

Hematopoietic stem and progenitor cells (HSPCs) acquire somatic mutations with age resulting in a heterogeneous cell population, with each HSPC possessing its own unique set of private mutations. HSPCs that acquire somatic mutations that confer a competitive fitness advantage relative to their normal counterparts may clonally expand. Indeed, several groups have documented the presence of clonal hematopoiesis in healthy individuals. Although originally thought to be limited to older individuals, a recent study using an ultra-sensitive sequencing technique showed that expanded hematopoietic clones are detectable in the majority of healthy 50-60-year-old individuals. With some notable exceptions, the same genes that are commonly mutated in clonal hematopoiesis also are somatically mutated in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, only a small fraction of individuals with clonal hematopoiesis subsequently develop a myeloid malignancy and the size of the mutant clone in clonal hematopoiesis can remain stable for years without disease progression. These observations raise several questions that will be addressed in this presentation. What drives expansion of hematopoietic clones? What role do external hematopoietic stressors, such as exposure to chemotherapy, play in the development of clonal hematopoiesis? Why do so few people with clonal hematopoiesis develop a myeloid malignancy, and are there certain mutations that confer a higher risk of transformation?

Disclosures

No relevant conflicts of interest to declare.
The fatty acid elongase ELOVL6 regulates bortezomib resistance in multiple myeloma
Authors: Lipchick Brittany C. , Utley Adam , Han Zhannan , Moparthy Sudha , Yun Dong Hyun , Bianchi-Smiraglia Anna , Wolff David W. , Fink Emily , Liu Liang , Furdui Cristina M. , Lee Jingyun , Lee Kelvin P. , Nikiforov Mikhail A.
Published: April 2021

Resistance to the proteasome inhibitor bortezomib (BTZ) represents a major obstacle in the treatment of multiple myeloma (MM). The contribution of lipid metabolism in the resistance of MM cells to BTZ is mostly unknown. Here we report that levels of fatty acid elongase 6 (ELOVL6) were lower in MM cells from BTZ-nonresponsive vs BTZ-responsive patients and in cultured MM cells selected for BTZ resistance compared with parental counterparts. Accordingly, depletion of ELOVL6 in parental MM cells suppressed BTZ-induced endoplasmic reticulum (ER) stress and cytotoxicity, whereas restoration of ELOVL6 levels in BTZ-resistant MM cells sensitized them to BTZ in tissue culture settings and, as xenografts, in a plasmacytoma mouse model. Furthermore, for the first time, we identified changes in the BTZ-induced lipidome between parental and BTZ-resistant MM cell lines underlying a functional difference in their response to BTZ. We demonstrated that restoration of ELOVL6 levels in BTZ-resistant MM cells resensitized them to BTZ largely via upregulation of ELOVL6-dependent ceramide species, which was a prerequisite for BTZ-induced ER stress and cell death in these cells. Our data characterize ELOVL6 as a major clinically relevant regulator of MM cell resistance to BTZ, which can emerge from the impaired ability of these cells to alter ceramide composition in response to BTZ.
The effect of platelet G proteins on platelet extravasation and tumor growth in the murine model of ovarian cancer
Authors: Cho Min Soon , Li Jiasong , Gonzalez-Delgado Ricardo , Lee Hani , Vasquez Matthew , He Tiancheng , He Yunjie , Liu Kai , Sasano Tomoyuki , Nürnberg Bernd , Sood Anil K. , Wong Stephen T. C. , Afshar-Kharghan Vahid
Published: April 2021

We and other investigators have shown that platelets promote metastasis and the growth of tumors. Our rationale for conducting this study is that platelets’ prometastatic and progrowth effects depend on a close encounter between platelets and cancer cells. This interaction occurs inside blood vessels with circulating tumor cells and outside blood vessels with cancer cells residing in the tumor parenchyma. Our hypothesis was that platelet extravasation is required for the effect of platelets on tumor growth. Platelets respond to environmental stimuli by activation of G protein–coupled receptors on their surface. We investigated the impact of various platelet G proteins on the growth of ovarian cancer tumors and platelet extravasation. We used mice with platelet-specific deficiency of Gαi2 (Gi), Gα13 (G13), or Gαq (Gq) in a syngeneic ovarian cancer model. We measured the total weight of tumor nodules resected from tumor-bearing mice. We developed methods for automated whole-slide image acquisition and unbiased computerized image analysis to quantify extravasated platelets. We compared the number of platelets inside tumor nodules of platelet G protein–deficient tumor-bearing mice. We found that deficiency of Gi and G13, but not Gq, in platelets resulted in smaller tumors compared with those in corresponding littermates. Deficiency of Gi and G13 in platelets reduced the number of extravasated platelets by >90%, but deficiency of Gq did not reduce the number of extravasated platelets significantly. The lack of Gi or G13 in platelets reduced platelet extravasation into the tumor and tumor growth.
New Guinean orogenic dynamics and biota evolution revealed using a custom geospatial analysis pipeline
Authors: Toussaint Emmanuel F. A. , White Lloyd T. , Shaverdo Helena , Lam Athena , Surbakti Suriani , Panjaitan Rawati , Sumoked Bob , von Rintelen Thomas , Sagata Katayo , Balke Michael
Published: April 2021

Background

The New Guinean archipelago has been shaped by millions of years of plate tectonic activity combined with long-term fluctuations in climate and sea level. These processes combined with New Guinea’s location at the tectonic junction between the Australian and Pacific plates are inherently linked to the evolution of its rich endemic biota. With the advent of molecular phylogenetics and an increasing amount of geological data, the field of New Guinean biogeography begins to be reinvigorated.

Results

We inferred a comprehensive dated molecular phylogeny of endemic diving beetles to test historical hypotheses pertaining to the evolution of the New Guinean biota. We used geospatial analysis techniques to compare our phylogenetic results with a newly developed geological terrane map of New Guinea as well as the altitudinal and geographic range of species (https://arcg.is/189zmz). Our divergence time estimations indicate a crown age (early diversification) for New Guinea Exocelina beetles in the mid-Miocene ca. 17 Ma, when the New Guinean orogeny was at an early stage. Geographic and geological ancestral state reconstructions suggest an origin of Exocelina ancestors on the eastern part of the New Guinean central range on basement rocks (with a shared affinity with the Australian Plate). Our results do not support the hypothesis of ancestors migrating to the northern margin of the Australian Plate from Pacific terranes that incrementally accreted to New Guinea over time. However, our analyses support to some extent a scenario in which Exocelina ancestors would have been able to colonize back and forth between the amalgamated Australian and Pacific terranes from the Miocene onwards. Our reconstructions also do not support an origin on ultramafic or ophiolite rocks that have been colonized much later in the evolution of the radiation. Macroevolutionary analyses do not support the hypothesis of heterogeneous diversification rates throughout the evolution of this radiation, suggesting instead a continuous slowdown in speciation.

Conclusions

Overall, our geospatial analysis approach to investigate the links between the location and evolution of New Guinea’s biota with the underlying geology sheds a new light on the patterns and processes of lineage diversification in this exceedingly diverse region of the planet.
Safety application of muscle relaxants and the traditional low-frequency ventilation during the flexible or rigid bronchoscopy in patients with central airway obstruction: a retrospective observational study
Authors: Li Jing-Jin , Li Nan , Ma Wei-Jia , Bao Ming-Xue , Chen Zi-Yang , Ding Zheng-Nian
Published: April 2021

Background

Bronchoscopy treatments of central airway obstruction (CAO) under general anesthesia are high-risky procedures, and posing a giant challenge to the anesthesiologists. We summarized and analyzed our clinical experience in patients with CAO undergoing flexible or rigid bronchoscopy, to estimate the safety of skeletal muscle relaxants application and the traditional Low-frequency ventilation.

Methods

Clinical data of 375 patients with CAO who underwent urgent endoscopic treatments in general anesthesia from January 2016 to October 2019 were retrospectively reviewed. The use ratio of skeletal muscle relaxants, dose of skeletal muscle relaxants used, the incidence of perioperative adverse events, adequacy of ventilation and gas exchange, post-operative recovery between rigid bronchoscopy and flexible bronchoscopy therapy, and risk factors for postoperative ICU admission were evaluated.

Results

Of the 375 patients with CAO, 204 patients were treated with flexible bronchoscopy and 171 patients were treated with rigid bronchoscopy. Muscle relaxants were used in 362 of 375 patients (including 313 cisatracurium, 45 rocuronium, 4 atracurium, and 13 unrecorded). The usage rate of muscle relaxants (96.5% in total) was very high in patients with CAO who underwent either flexible bronchoscopy (96.6%) or rigid bronchoscopy (96.5%) therapy. The dosage of skeletal muscle relaxants (Cisatracium) used was higher in rigid bronchoscopy compared with flexible bronchoscopy therapy (10.8 ± 3.8 VS 11.6 ± 3.6 mg, respectively,p < 0.05). No patient suffered the failure of ventilation, bronchospasm and intraoperative cough either in flexible or rigid bronchoscopy therapy. Hypoxemia was occurred in 13 patients (8 in flexible, 5 in rigid bronchoscopy) during the procedure, and reintubation after extubation happened in 2 patients with flexible bronchoscopy. Sufficient ventilation was successfully established using the traditional Low-frequency ventilation with no significant carbon dioxide accumulation and hypoxemia occurred both in flexible and rigid bronchoscopy group (p > 0.05). Three patients (1 in flexible and 2 in rigid) died, during the post-operative recovery, and the higher grade of American Society of Anesthesiologists (ASA) and obvious dyspnea or orthopnea were the independent risk factors for postoperative ICU admission.

Conclusion

The muscle relaxants and low-frequency traditional ventilation can be safely used both in flexible and rigid bronchoscopy treatments in patients with CAO. These results may provide strong clinical evidence for optimizing the anesthesia management of bronchoscopy for these patients.
Seasonality in extra-pulmonary tuberculosis notifications in Germany 2004-2014- a time series analysis
Authors: Charles Tanja , Eckardt Matthias , Karo Basel , Haas Walter , Kröger Stefan
Published: April 2021

Background

Seasonality in tuberculosis (TB) has been found in different parts of the world, showing a peak in spring/summer and a trough in autumn/winter. The evidence is less clear which factors drive seasonality. It was our aim to identify and evaluate seasonality in the notifications of TB in Germany, additionally investigating the possible variance of seasonality by disease site, sex and age group.

Methods

We conducted an integer-valued time series analysis using national surveillance data. We analysed the reported monthly numbers of started treatments between 2004 and 2014 for all notified TB cases and stratified by disease site, sex and age group.

Results

We detected seasonality in the extra-pulmonary TB cases (N = 11,219), with peaks in late spring/summer and troughs in fall/winter. For all TB notifications together (N = 51,090) and for pulmonary TB only (N = 39,714) we did not find a distinct seasonality. Additional stratified analyses did not reveal any clear differences between age groups, the sexes, or between active and passive case finding.

Conclusion

We found seasonality in extra-pulmonary TB only, indicating that seasonality of disease onset might be specific to the disease site. This could point towards differences in disease progression between the different clinical disease manifestations. Sex appears not to be an important driver of seasonality, whereas the role of age remains unclear as this could not be sufficiently investigated.
Second sacral sacralalar‐iliac (S2AI) screw placement in adult degenerative scoliosis (ADS) patients: an imaging study
Authors: Wu Bing , Song Kai , Cheng Junyao , Chi Pengfei , Wang Zhaohan , Wang Zheng
Published: April 2021

Background

The imaging characteristics of sacral sacralalar-iliac (S2AI) screw trajectory in adult degenerative scoliosis (ADS) patients will be determined.

Methods

S2AI screw trajectories were mapped on three-dimensional computed tomography (3DCT) reconstructions of 40 ADS patients. The starting point, placement plane, screw template, and a circle centered at the lowest point of the ilium inner cortex were set on these images. A tangent line from the starting point to the outer diameter of the circle was selected as the axis of the screw trajectory. The related parameters in different populations were analyzed and compared.

Results

The trajectory length of S2AI screws in ADS patients was 12.00 ± 0.99 cm, the lateral angle was 41.24 ± 3.92°, the caudal angle was 27.73 ± 6.45°, the distance from the axis of the screw trajectory to the iliosciatic notch was 1.05 ± 0.81 cm, the distance from the axis of the screw trajectory to the upper edge of the acetabulum was 1.85 ± 0.33 cm, and the iliac width was 2.12 ± 1.65 cm. Compared with females, the lateral angle of male ADS patients was decreased, but the trajectory length was increased (P < 0.05). Compared to patients without ADS in previous studies, the lateral angle of male patients was larger, the lateral angle of female patients was increased, and the caudal angle was decreased (P < 0.05).

Conclusions

There is an ideal trajectory of S2AI screws in ADS patients. A different direction should be noticed in the placement of S2AI screws, especially in female patients.
Waking experience modulates sleep need in mice
Authors: Milinski Linus , Fisher Simon P. , Cui Nanyi , McKillop Laura E. , Blanco-Duque Cristina , Ang Gauri , Yamagata Tomoko , Bannerman David M. , Vyazovskiy Vladyslav V.
Published: April 2021

Background

Homeostatic regulation of sleep is reflected in the maintenance of a daily balance between sleep and wakefulness. Although numerous internal and external factors can influence sleep, it is unclear whether and to what extent the process that keeps track of time spent awake is determined by the content of the waking experience. We hypothesised that alterations in environmental conditions may elicit different types of wakefulness, which will in turn influence both the capacity to sustain continuous wakefulness as well as the rates of accumulating sleep pressure. To address this, we compared the effects of repetitive behaviours such as voluntary wheel running or performing a simple touchscreen task, with wakefulness dominated by novel object exploration, on sleep timing and EEG slow-wave activity (SWA) during subsequent NREM sleep.

Results

We find that voluntary wheel running is associated with higher wake EEG theta-frequency activity and results in longer wake episodes, as compared with exploratory behaviour; yet, it does not lead to higher levels of EEG SWA during subsequent NREM sleep in either the frontal or occipital derivation. Furthermore, engagement in a touchscreen task, motivated by food reward, results in lower SWA during subsequent NREM sleep in both derivations, as compared to exploratory wakefulness, even though the total duration of wakefulness is similar.

Conclusion

Overall, our study suggests that sleep-wake behaviour is highly flexible within an individual and that the homeostatic processes that keep track of time spent awake are sensitive to the nature of the waking experience. We therefore conclude that sleep dynamics are determined, to a large degree, by the interaction between the organism and the environment.
Screening of gene markers related to the prognosis of metastatic skin cutaneous melanoma based on Logit regression and survival analysis
Authors: Jia Guoliang , Song Zheyu , Xu Zhonghang , Tao Youmao , Wu Yuanyu , Wan Xiaoyu
Published: April 2021

Background

Bioinformatics was used to analyze the skin cutaneous melanoma (SKCM) gene expression profile to provide a theoretical basis for further studying the mechanism underlying metastatic SKCM and the clinical prognosis.

Methods

We downloaded the gene expression profiles of 358 metastatic and 102 primary (nonmetastatic) CM samples from The Cancer Genome Atlas (TCGA) database as a training dataset and the GSE65904 dataset from the National Center for Biotechnology Information database as a validation dataset. Differentially expressed genes (DEGs) were screened using the limma package of R3.4.1, and prognosis-related feature DEGs were screened using Logit regression (LR) and survival analyses. We also used the STRING online database, Cytoscape software, and Database for Annotation, Visualization and Integrated Discovery software for protein–protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on the screened DEGs.

Results

Of the 876 DEGs selected, 11 (ZNF750, NLRP6, TGM3, KRTDAP, CAMSAP3, KRT6C, CALML5, SPRR2E, CD3G, RTP5, and FAM83C) were screened using LR analysis. The survival prognosis of nonmetastatic group was better compared to the metastatic group between the TCGA training and validation datasets. The 11 DEGs were involved in 9 KEGG signaling pathways, and of these 11 DEGs, CALML5 was a feature DEG involved in the melanogenesis pathway, 12 targets of which were collected.

Conclusion

The feature DEGs screened, such as CALML5, are related to the prognosis of metastatic CM according to LR. Our results provide new ideas for exploring the molecular mechanism underlying CM metastasis and finding new diagnostic prognostic markers.
How prepared is Mozambique to treat COVID-19 patients? A new approach for estimating oxygen service availability, oxygen treatment capacity, and population access to oxygen-ready treatment facilities
Authors: Denhard Langan , Kaviany Parisa , Chicumbe Sérgio , Muianga Cláudio , Laisse Guitunga , Aune Kyle , Sheffel Ashley
Published: April 2021

Background

This study aims to assess the COVID-19 response preparedness of the Mozambican health system by 1) determining the location of oxygen-ready public health facilities, 2) estimating the oxygen treatment capacity, and 3) determining the population coverage of oxygen-ready health facilities in Mozambique.

Methods

This analysis utilizes information on the availability of oxygen sources and delivery apparatuses to determine if a health facility is ready to deliver oxygen therapy to patients in need, and estimates how many patients can be treated with continuous oxygen flow for a 7-day period based on the available oxygen equipment at health facilities. Using GIS mapping software, the study team modeled varying travel times to oxygen-ready facilities to estimate the proportion of the population with access to care.

Results

0.4% of all health facilities in Mozambique are prepared to deliver oxygen therapy to patients, for a cumulative total of 283.9 to 406.0 patients-weeks given the existing national capacity, under varying assumptions including ability to divert oxygen from a single source to multiple patients. 35% of the population in Mozambique has adequate access within one-hour driving time of an oxygen-ready health facility. This varies widely by region; 89.1% of the population of Maputo City was captured by the one-hour driving time network, as compared ot 4.4% of the population of Niassa province.

Conclusions

The Mozambican health system faces the dual challenges of under-resourced health facilities and low geographic accessibility to healthcare as it prepares to confront the COVID-19 pandemic. This analysis also illustrates the disparity between provinces in preparedness to deliver oxygen therapy to patient, with Cabo Delgado and Nampula being particularly under-resourced.
The influence of corporate market power on health: exploring the structure-conduct-performance model from a public health perspective
Authors: Wood Benjamin , Williams Owain , Baker Phil , Nagarajan Vijaya , Sacks Gary
Published: April 2021

Background

The detrimental impact of dominant corporations active in health-harming commodity industries is well recognised. However, to date, existing analyses of the ways in which corporations influence health have paid limited attention to corporate market power. Accordingly, the public health implications of concentrated market structures, the use of anti-competitive market strategies, and the ways in which market power mediates the allocation and distribution of resources via market systems, remain relatively unexplored. To address this gap, this paper aimed to identify and explore key literature that could inform a comprehensive framework to examine corporate market power from a public health perspective. The ultra-processed food (UPF) industry was used to provide illustrative examples.

Methods

A scoping review of a diverse range of literature, including Industrial Organization, welfare economics, global political economy and antitrust policy, was conducted to identify important concepts and metrics that could be drawn upon within the field of public health to understand and explore market power. The Structure-Conduct-Performance (SCP) model, a guiding principle of antitrust policy and the regulation of market power, was used as an organising framework.

Results

We described each of the components of the traditional SCP model and how they have historically been used to assess market power through examining the interrelations between the structure of industries and markets, the conduct of dominant firms, and the overall ability of markets and firms to efficiently allocate and distribute the scarce resources.

Conclusion

We argue that the SCP model is well-placed to broaden public health research into the ways in which corporations influence health. In addition, the development of a comprehensive framework based on the key findings of this paper could help the public health community to better engage with a set of policy and regulatory tools that have the potential to curb the concentration of corporate power for the betterment of population health.
Strengthening healthcare providers’ capacity for safe abortion and post-abortion care services in humanitarian settings: lessons learned from the clinical outreach refresher training model (S-CORT) in Uganda, Nigeria, and the Democratic Republic of Congo
Authors: Tran Nguyen Toan , Greer Alison , Dah Talemoh , Malilo Bibiche , Kakule Bergson , Morisho Thérèse Faila , Asifiwe Douglass Kambale , Musa Happiness , Simon Japheth , Meyers Janet , Noznesky Elizabeth , Neusy Sarah , Vranovci Burim , Powell Bill
Published: April 2021

Background

Fragile and crisis-affected countries account for most maternal deaths worldwide, with unsafe abortion being one of its leading causes. This case study aims to describe the Clinical Outreach Refresher Training strategy for sexual and reproductive health (S-CORT) designed to update health providers’ competencies on uterine evacuation using both medications and manual vacuum aspiration. The paper also explores stakeholders’ experiences, recommendations for improvement, and lessons learned.

Methods

Using mixed methods, we evaluated three training workshops that piloted the uterine evacuation module in 2019 in humanitarian contexts of Uganda, Nigeria, and the Democratic Republic of Congo.

Results

Results from the workshops converged to suggest that the module contributed to increasing participants’ theoretical knowledge and possibly technical and counseling skills. Equally noteworthy were their confidence building and positive attitudinal changes promoting a rights-based, fearless, non-judgmental, and non-discriminatory approach toward clients. Participants valued the hands-on, humanistic, and competency-based training methodology, although most regretted the short training duration and lack of practice on real clients. Recommendations to improve the capacity development continuum of uterine evacuation included recruiting the appropriate health cadres for the training; sharing printed pre-reading materials to all participants; sustaining the availability of medication and supplies to offer services to clients after the training; and helping staff through supportive supervision visits to accelerate skills transfer from training to clinic settings.

Conclusions

When the lack of skilled human resources is a barrier to lifesaving uterine evacuation services in humanitarian settings, the S-CORT strategy could offer a rapid hands-on refresher training opportunity for service providers needing an update in knowledge and skills. Such a capacity-building approach could be useful in humanitarian and fragile settings as well as in development settings with limited resources as part of an overall effort to strengthen other building blocks of the health system.
Novel therapies emerging in oncology to target the TGF-β pathway
Authors: Kim Byung-Gyu , Malek Ehsan , Choi Sung Hee , Ignatz-Hoover James J. , Driscoll James J.
Published: April 2021

The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Collectively, the pleiotropic nature of TGF-β signaling contributes to drug resistance, tumor escape and undermines clinical response to therapy. Based upon a wealth of preclinical studies, the TGF-β pathway has been pharmacologically targeted using small molecule inhibitors, TGF-β-directed chimeric monoclonal antibodies, ligand traps, antisense oligonucleotides and vaccines that have been now evaluated in clinical trials. Here, we have assessed the safety and efficacy of TGF-β pathway antagonists from multiple drug classes that have been evaluated in completed and ongoing trials. We highlight Vactosertib, a highly potent small molecule TGF-β type 1 receptor kinase inhibitor that is well-tolerated with an acceptable safety profile that has shown efficacy against multiple types of cancer. The TGF-β ligand traps Bintrafusp alfa (a bifunctional conjugate that binds TGF-β and PD-L1), AVID200 (a computationally designed trap of TGF-β receptor ectodomains fused to an Fc domain) and Luspatercept (a recombinant fusion that links the activin receptor IIb to IgG) offer new ways to fight difficult-to-treat cancers. While TGF-β pathway antagonists are rapidly emerging as highly promising, safe and effective anticancer agents, significant challenges remain. Minimizing the unintentional inhibition of tumor-suppressing activity and inflammatory effects with the desired restraint on tumor-promoting activities has impeded the clinical development of TGF-β pathway antagonists. A better understanding of the mechanistic details of the TGF-β pathway should lead to more effective TGF-β antagonists and uncover biomarkers that better stratify patient selection, improve patient responses and further the clinical development of TGF-β antagonists.
Correction to: Ventilator-associated pneumonia in critically ill patients with COVID-19
Authors: Maes Mailis , Higginson Ellen , Pereira-Dias Joana , Curran Martin D. , Parmar Surendra , Khokhar Fahad , Cuchet-Lourenço Delphine , Lux Janine , Sharma-Hajela Sapna , Ravenhill Benjamin , Hamed Islam , Heales Laura , Mahroof Razeen , Soderholm Amelia , Forrest Sally , Sridhar Sushmita , Brown Nicholas M. , Baker Stephen , Navapurkar Vilas , Dougan Gordon , Scott Josefn Bartholdson , Morris Andrew Conway
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Phase-IIa randomized, double-blind, sham-controlled, parallel group trial on anodal transcranial direct current stimulation (tDCS) over the left and right tempo-parietal junction in autism spectrum disorder—StimAT: study protocol for a clinical trial
Authors: Luckhardt Christina , Schütz Magdalena , Mühlherr Andreas , Mössinger Hannah , Boxhoorn Sara , Dempfle Astrid , Salvador Ricardo , Ruffini Giulio , Pereira Helena C. , Castelo-Branco Miguel , Latinus Marianne , Bonnet-Brilhault Frédérique , Siemann Julia , Siniatchkin Michael , Ecker Christine , Freitag Christine M.
Published: April 2021

Background

Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction, and stereotyped, repetitive behaviour and sensory interests. To date, there is no effective medication that can improve social communication and interaction in ASD, and effect sizes of behaviour-based psychotherapy remain in the low to medium range. Consequently, there is a clear need for new treatment options. ASD is associated with altered activation and connectivity patterns in brain areas which process social information. Transcranial direct current stimulation (tDCS) is a technique that applies a weak electrical current to the brain in order to modulate neural excitability and alter connectivity. Combined with specific cognitive tasks, it allows to facilitate and consolidate the respective training effects. Therefore, application of tDCS in brain areas relevant to social cognition in combination with a specific cognitive training is a promising treatment approach for ASD.

Methods

A phase-IIa pilot randomized, double-blind, sham-controlled, parallel-group clinical study is presented, which aims at investigating if 10 days of 20-min multi-channel tDCS stimulation of the bilateral tempo-parietal junction (TPJ) at 2.0 mA in combination with a computer-based cognitive training on perspective taking, intention and emotion understanding, can improve social cognitive abilities in children and adolescents with ASD. The main objectives are to describe the change in parent-rated social responsiveness from baseline (within 1 week before first stimulation) to post-intervention (within 7 days after last stimulation) and to monitor safety and tolerability of the intervention. Secondary objectives include the evaluation of change in parent-rated social responsiveness at follow-up (4 weeks after end of intervention), change in other ASD core symptoms and psychopathology, social cognitive abilities and neural functioning post-intervention and at follow-up in order to explore underlying neural and cognitive mechanisms.

Discussion

If shown, positive results regarding change in parent-rated social cognition and favourable safety and tolerability of the intervention will confirm tDCS as a promising treatment for ASD core-symptoms. This may be a first step in establishing a new and cost-efficient intervention for individuals with ASD.

Trial registration

The trial is registered with the German Clinical Trials Register (DRKS), DRKS00014732. Registered on 15 August 2018.

Protocol version

This study protocol refers to protocol version 1.2 from 24 May 2019.
Correction to: Single-cell transcriptome conservation in a comparative analysis of fresh and cryopreserved human skin tissue: pilot in localized scleroderma
Authors: Mirizio Emily , Tabib Tracy , Wang Xinjun , Chen Wei , Liu Christopher , Lafyatis Robert , Jacobe Heidi , Torok Kathryn S.
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Effect of combined pulmonary fibrosis and emphysema on patients with connective tissue diseases and systemic sclerosis: a systematic review and meta-analysis
Authors: Koo Bon San , Park Kyu Yong , Lee Hyun Jung , Kim Hyun Jung , Ahn Hyeong Sik , Yim Shin-Young , Jun Jae-Bum
Published: April 2021

Background

This study aimed to analyze the literature systematically to determine the clinical characteristics and prognosis of patients with connective tissue disease (CTD) with combined pulmonary fibrosis and emphysema (CPFE) compared to those of patients with CTD-interstitial lung disease (CTD-ILD) without emphysema.

Methods

We searched MEDLINE, EMBASE, Cochrane Library, and KoreaMed for relevant articles published before July 2019. Studies meeting all the following criteria were included: (1) original research studies evaluating the effect of CPFE on CTD, (2) studies that compared patients with CTD-CPFE to those with CTD-ILD without emphysema, and (3) studies providing data on physical capacity, pulmonary function, or death in patients with CTD. Clinical characteristics of patients with CTD-CPFE were compared with those of patients with CTD-ILD without emphysema, and the influence of CPFE on physical capacity, pulmonary function, and death was analyzed.

Results

Six studies between 2013 and 2019 were included. Two hundred ninety-nine (29.5%) and 715 (70.5%) patients had CTD-CPFE and CTD-ILD without emphysema, respectively. Regarding the type of CTD, 711 (68.3%) patients had systemic sclerosis, 263 (25.3%) rheumatoid arthritis, and 67 (6.4%) other CTDs. Patients with CTD-CPFE had a higher frequency of pulmonary hypertension and pulmonary fibrosis > 20% of the total lung volume, higher ratio of the forced vital capacity to the diffusion capacity of the lung for carbon monoxide (DLCO), lower arterial oxygen pressure at rest, and lower DLCO compared to those in patients with CTD-ILD without emphysema. In addition, more deaths occurred among those with CTD-CPFE (odds ratio, 2.95; 95% confidence interval, 1.75–4.96).

Conclusion

CTD-CPFE is associated with worse physical and pulmonary function and more deaths compared to those in CTD-ILD without emphysema. These findings indicate the need for increased awareness and close monitoring of patients with CTD-CPFE.
Posterior fossa extra-axial variations of medulloblastoma: a pictorial review as a primer for radiologists
Authors: Al-Sharydah Abdulaziz M. , Al-Abdulwahhab Abdulrahman Hamad , Al-Suhibani Sari Saleh , Al-Issawi Wisam M. , Al-Zahrani Faisal , Katbi Faisal Ahmad , Al-Thuneyyan Moath Abdullah , Jallul Tarek , Mishaal Alabbas Faisal
Published: April 2021

Manifestations of an atypical variant of medulloblastoma of the posterior fossa in extra-axial locations have been reported, and key questions concerning its interpretation have been raised previously. This review illustrated the clinico-radiological and histopathological features of the posterior fossa extra-axial medulloblastoma and described possible management strategies. We thoroughly reviewed all atypical anatomical locations of medulloblastoma reported within the posterior fossa and extra-axial spaces. The main characteristics of diagnostic imaging and histopathological results, primarily the distinctive radiopathological characteristics, were summarized to distinguish between intra- and extra-axial medulloblastoma, or pathologies mimicking this tumor. Most cases of posterior fossa extra-axial medulloblastoma have been reported in the cerebellopontine angle, followed by the tentorial and lateral cerebellar locations. The dural tail sign, which is commonly observed in meningioma, is rarely seen in intra- or extra-axial medulloblastoma and might be associated with other benign or malignant lesions. In addition to magnetic resonance imaging, the proposed new imaging techniques, including advances in modern neuroimaging modalities, were discussed, as potentially efficient modalities for characterizing extra-axial medulloblastoma. Radionuclide imaging and magnetic resonance perfusion imaging are practical alternatives to limit the number of differential diagnoses. We believe that medulloblastoma cases are likely under-reported because of publication bias and frequent tumors in unusual locations. Addressing these issues would help establish a more accurate understanding of this entity.
RETRACTED ARTICLE: Practical application of wireless communication network multimedia courseware in college basketball teaching
Authors: Chen Wengang , Wang Fang
Published: April 2021

With the acceleration of informatization and the coverage of wireless networks, homes, conferences, schools and other places have a higher pursuit of the wireless transmission capabilities of electronic devices. Wireless screen transmission technology is used more frequently in life, work and study. This article mainly discusses the practical application of network multimedia courseware in college basketball teaching. This article first elaborates the teaching plan of multimedia courseware, including teaching content, teacher guidance, student learning and multimedia courseware. Secondly, the multimedia courseware of basketball tactics basic teaching is completed by using Flash mx2004 plug-in. After that, it specifically introduces the process of how to transmit basketball teaching content through multimedia equipment to the video network for students to learn under the wireless network environment. It emphasizes that the “wireless multimedia communication” course is an important course in the electronic information subject. Finally, through the teaching experiment, the accuracy of the multimedia teaching method was tested, and the validity of the courseware content was tested by the empirical validity evaluation method. At the same time, after the teaching experiment, in order to test the two groups of students’ mastery of the basic coordination theory of basketball tactics, the basic coordination theory of basketball tactics was tested. The experimental group had 22 students with a score of 90 or more, accounting for 27.5%, and the control group had 13 students with a score of 90 or more, accounting for 16.5%. The results show that wireless network multimedia computer-assisted teaching has a positive effect on improving students’ interest in learning.
On weighted means and their inequalities
Authors: Raïssouli Mustapha , Furuichi Shigeru
Published: April 2021

In (Pal et al. in Linear Multilinear Algebra 64(12):2463–2473, 2016), Pal et al. introduced some weighted means and gave some related inequalities by using an approach for operator monotone functions. This paper discusses the construction of these weighted means in a simple and nice setting that immediately leads to the inequalities established there. The related operator version is here immediately deduced as well. According to our constructions of the means, we study all cases of the weighted means from three weighted arithmetic/geometric/harmonic means by the use of the concept such as stable and stabilizable means. Finally, the power symmetric means are studied and new weighted power means are given.
Executing cyclic scientific workflows in the cloud
Authors: Krämer Michel , Würz Hendrik M. , Altenhofen Christian
Published: April 2021

We present an algorithm and a software architecture for a cloud-based system that executes cyclic scientific workflows whose structure may change during run time. Existing approaches either rely on workflow definitions based on directed acyclic graphs (DAGs) or require workarounds to implement cyclic structures. In contrast, our system supports cycles natively, avoids workarounds, and as such reduces the complexity of workflow modelling and maintenance. Our algorithm traverses workflow graphs and transforms them iteratively into linear sequences of executable actions. We call these sequences process chains. Our software architecture distributes the process chains to multiple compute nodes in the cloud and oversees their execution. We evaluate our approach by applying it to two practical use cases from the domains of astronomy and engineering. We also compare it with two existing workflow management systems. The evaluation demonstrates that our algorithm is able to execute dynamically changing workflows with cycles and that design and maintenance of complex workflows is easier than with existing solutions. It also shows that our software architecture can run process chains on multiple compute nodes in parallel to significantly speed up the workflow execution. An implementation of our algorithm and the software architecture is available with the Steep Workflow Management System that we released under an open-source license. The resources for the first practical use case are also available as open source for reproduction.
Health anxiety, perceived stress, and coping styles in the shadow of the COVID-19
Authors: Garbóczy Szabolcs , Szemán-Nagy Anita , Ahmad Mohamed S. , Harsányi Szilvia , Ocsenás Dorottya , Rekenyi Viktor , Al-Tammemi Ala’a B. , Kolozsvári László Róbert
Published: April 2021

Background

In the case of people who carry an increased number of anxiety traits and maladaptive coping strategies, psychosocial stressors may further increase the level of perceived stress they experience. In our research study, we aimed to examine the levels of perceived stress and health anxiety as well as coping styles among university students amid the COVID-19 pandemic.

Methods

A cross-sectional study was conducted using an online-based survey at the University of Debrecen during the official lockdown in Hungary when dormitories were closed, and teaching was conducted remotely. Our questionnaire solicited data using three assessment tools, namely, the Perceived Stress Scale (PSS), the Ways of Coping Questionnaire (WCQ), and the Short Health Anxiety Inventory (SHAI).

Results

A total of 1320 students have participated in our study and 31 non-eligible responses were excluded. Among the remaining 1289 participants, 948 (73.5%) and 341 (26.5%) were Hungarian and international students, respectively. Female students predominated the overall sample with 920 participants (71.4%). In general, there was a statistically significant positive relationship between perceived stress and health anxiety. Health anxiety and perceived stress levels were significantly higher among international students compared to domestic ones. Regarding coping, wishful thinking was associated with higher levels of stress and anxiety among international students, while being a goal-oriented person acted the opposite way. Among the domestic students, cognitive restructuring as a coping strategy was associated with lower levels of stress and anxiety. Concerning health anxiety, female students (domestic and international) had significantly higher levels of health anxiety compared to males. Moreover, female students had significantly higher levels of perceived stress compared to males in the international group, however, there was no significant difference in perceived stress between males and females in the domestic group.

Conclusion

The elevated perceived stress levels during major life events can be further deepened by disengagement from home (being away/abroad from country or family) and by using inadequate coping strategies. By following and adhering to the international recommendations, adopting proper coping methods, and equipping oneself with the required coping and stress management skills, the associated high levels of perceived stress and anxiety could be mitigated.
Identifying resting locations of a small elusive forest carnivore using a two-stage model accounting for GPS measurement error and hidden behavioral states
Authors: Hance Dalton J. , Moriarty Katie M. , Hollen Bruce A. , Perry Russell W.
Published: April 2021

Background

Studies of animal movement using location data are often faced with two challenges. First, time series of animal locations are likely to arise from multiple behavioral states (e.g., directed movement, resting) that cannot be observed directly. Second, location data can be affected by measurement error, including failed location fixes. Simultaneously addressing both problems in a single statistical model is analytically and computationally challenging. To both separate behavioral states and account for measurement error, we used a two-stage modeling approach to identify resting locations of fishers (Pekania pennanti) based on GPS and accelerometer data.

Methods

We developed a two-stage modelling approach to estimate when and where GPS-collared fishers were resting for 21 separate collar deployments on 9 individuals in southern Oregon. For each deployment, we first fit independent hidden Markov models (HMMs) to the time series of accelerometer-derived activity measurements and apparent step lengths to identify periods of movement and resting. Treating the state assignments as given, we next fit a set of linear Gaussian state space models (SSMs) to estimate the location of each resting event.

Results

Parameter estimates were similar across collar deployments. The HMMs successfully identified periods of resting and movement with posterior state assignment probabilities greater than 0.95 for 97% of all observations. On average, fishers were in the resting state 63% of the time. Rest events averaged 5 h (4.3 SD) and occurred most often at night. The SSMs allowed us to estimate the 95% credible ellipses with a median area of 0.12 ha for 3772 unique rest events. We identified 1176 geographically distinct rest locations; 13% of locations were used on > 1 occasion and 5% were used by > 1 fisher. Females and males traveled an average of 6.7 (3.5 SD) and 7.7 (6.8 SD) km/day, respectively.

Conclusions

We demonstrated that if auxiliary data are available (e.g., accelerometer data), a two-stage approach can successfully resolve both problems of latent behavioral states and GPS measurement error. Our relatively simple two-stage method is repeatable, computationally efficient, and yields directly interpretable estimates of resting site locations that can be used to guide conservation decisions.
Ligand-modulated synthesis of gold nanoclusters for sensitive and selective detection of folic acid
Authors: Li Xiangfei , Qiao Juan , Sun Yongjun , Li Zhiwei , Qi Li
Published: April 2021

Precisely changing the optical properties of gold nanoclusters (AuNCs) with different ligands offers a promising prospect for highly sensitive and selective drug sensing. In this study, AuNCs were synthesized with d-tryptophan (d-Trp) and its derivatives as the ligands. Optical measurements showed that d-Trp@AuNCs produced higher fluorescence intensity and shorter fluorescence emission wavelength than the d-Trp-derivatives-ligands protected AuNCs, indicating that the ligand-shell rigidity and core-shell charge transfer affected their fluorescent properties. At the excitation wavelength of 370 nm, the emission wavelength of d-Trp@AuNCs was 460 nm. The fluorescence changes revealed the high selectivity of d-Trp@AuNCs for detecting folic acid due to the static quenching and inner filter effect. In the presence of folic acid, the fluorescence of d-Trp@AuNCs was remarkably quenched with good linearity ranging from 6.3-100.0 μM (R2 = 0.997) and a detection limit of 5.8 μM. The proposed assay was successfully utilized to determine the amount of folic acid in human urine with recoveries from 94.3 to 107.3%. This work shows the great potential of d-Trp@AuNCs for detecting folic acid in real bio-samples. It also presents an effective strategy for preparation of the AuNCs with enhanced fluorescence efficiency by regulating the rigidity of the ligands shell and the core-shell charge transfer.