bluuebunny/crossref_metadata_2025 huggingface dataset:
Early and late stage MPN patients show distinct gene expression profiles in CD34+ cells
Authors: Baumeister Julian , Maié Tiago , Chatain Nicolas , Gan Lin , Weinbergerova Barbora , de Toledo Marcelo A. S. , Eschweiler Jörg , Maurer Angela , Mayer Jiri , Kubesova Blanka , Racil Zdenek , Schuppert Andreas , Costa Ivan , Koschmieder Steffen , Brümmendorf Tim H. , Gezer Deniz
Published: August 2021

Myeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing–associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN.

Graphical abstract
Moisture recycling and the potential role of forests as moisture source during European heatwaves
Authors: Pranindita Agnes , Wang-Erlandsson Lan , Fetzer Ingo , Teuling Adriaan J.
Published: August 2021

Heatwaves are extreme weather events that have become more frequent and intense in Europe over the past decades. Heatwaves are often coupled to droughts. The combination of them lead to severe ecological and socio-economic impacts. Heatwaves can self-amplify through internal climatic feedback that reduces local precipitation. Understanding the terrestrial sources of local precipitation during heatwaves might help identify mitigation strategies on land management and change that alleviate impacts. Moisture recycling of local water sources through evaporation allows a region to maintain precipitation in the same region or, by being transported by winds, in adjacent regions. To understand the role of terrestrial moisture sources for sustaining precipitation during heatwaves, we backtrack and analyse the precipitation sources of Northern, Western, and Southern sub-regions across Europe during 20 heatwave periods between 1979 and 2018 using the moisture tracking model Water Accounting Model-2layers (WAM-2layers). In Northern and Western Europe, we find that stabilizing anticyclonic patterns reduce the climatological westerly supply of moisture, mainly from the North Atlantic Ocean, and enhances the moisture flow from the eastern Euro-Asian continent and from within their own regions—suggesting over 10% shift of moisture supply from oceanic to terrestrial sources. In Southern Europe, limited local moisture sources result in a dramatic decrease in the local moisture recycling rate. Forests uniformly supply additional moisture to all regions during heatwaves and thus contribute to buffer local impacts. This study suggests that terrestrial moisture sources, especially forests, may potentially be important to mitigate moisture scarcity during heatwaves in Europe.
Mitochondrial nucleoid in cardiac homeostasis: bidirectional signaling of mitochondria and nucleus in cardiac diseases
Authors: Feng Yuliang , Huang Wei , Paul Christian , Liu Xingguo , Sadayappan Sakthivel , Wang Yigang , Pauklin Siim
Published: August 2021

Metabolic function and energy production in eukaryotic cells are regulated by mitochondria, which have been recognized as the intracellular ‘powerhouses’ of eukaryotic cells for their regulation of cellular homeostasis. Mitochondrial function is important not only in normal developmental and physiological processes, but also in a variety of human pathologies, including cardiac diseases. An emerging topic in the field of cardiovascular medicine is the implication of mitochondrial nucleoid for metabolic reprogramming. This review describes the linear/3D architecture of the mitochondrial nucleoid (e.g., highly organized protein-DNA structure of nucleoid) and how it is regulated by a variety of factors, such as noncoding RNA and its associated R-loop, for metabolic reprogramming in cardiac diseases. In addition, we highlight many of the presently unsolved questions regarding cardiac metabolism in terms of bidirectional signaling of mitochondrial nucleoid and 3D chromatin structure in the nucleus. In particular, we explore novel techniques to dissect the 3D structure of mitochondrial nucleoid and propose new insights into the mitochondrial retrograde signaling, and how it regulates the nuclear (3D) chromatin structures in mitochondrial diseases.
Endurance training-induced increase in muscle oxidative capacity without loss of muscle mass in younger and older resistance-trained men
Authors: Hendrickse Paul William , Venckunas Tomas , Platkevicius Justinas , Kairaitis Ramutis , Kamandulis Sigitas , Snieckus Audrius , Stasiulis Arvydas , Vitkiene Jolanta , Subocius Andrejus , Degens Hans
Published: August 2021

While concurrent training is regularly used in older populations, the inverse relationship between fibre size and oxidative capacity suggests that endurance training in resistance-trained individuals may result in some loss of resistance training-induced gains in muscle mass, which may be more pronounced in older people. We investigated the impact of superimposed endurance training in younger (28.5 ± 4.8 years; n = 8) and older (67.5 ± 5.5 years; n = 7) highly resistance-trained men. Participants underwent a 10-week endurance cycling training programme consisting of five 6-min intervals at 75% max heart rate (HRmax) separated by 4-min intervals at 90% HRmax. The anatomical cross-sectional area (ACSA) of the thigh muscles, as determined with MRI, was 24% smaller in older compared to younger participants (p < 0.001). Although maximal oxygen consumption (VO2max) was also lower in the older group (p < 0.001), VO2max per kg body mass did not differ significantly between younger and older participants. Histological analyses of biopsies of the m. vastus lateralis showed that endurance training induced an increase in succinate dehydrogenase activity in both younger and older participants (p ≤ 0.043), and an increase in the number of capillaries around type I fibres (p = 0.017). The superimposed endurance training did not induce a significant decrease in thigh ACSA, fibre cross-sectional area, or knee extensor maximum voluntary isometric force. These observations indicate that adding endurance training to resistance training can lead to positive endurance-related adaptations without negative consequences for muscle size and strength in older and younger resistance-trained people.
Rapidly fatal SMARCA4-deficient undifferentiated sarcoma originating from hybrid hemosiderotic fibrolipomatous tumor/pleomorphic hyalinizing angiectatic tumor of the foot
Authors: Agaimy Abbas , Meidenbauer Norbert , Sukov William R. , Stoehr Robert , Vieth Michael , Roemer Frank , Grützmann Robert , Folpe Andrew L.
Published: August 2021

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts and hemosiderotic fibrolipomatous tumor (HFLT) are two rare low-grade locally recurring neoplasms with predilection for the foot/ankle. Recent studies support a close link between the two entities, and origin of PHAT from HFLT and occurrence of hybrid HFLT/PHAT have been documented. Both lesions often harbor TGFBR3 or MGEA5 rearrangements. Rare sarcomas originating from HFLT/PHAT have been reported, typically resembling myxofibrosarcoma or myxoinflammatory fibroblastic sarcoma. We describe a novel SMARCA4-deficient undifferentiated sarcoma with rhabdoid features originating from hybrid HFLT/PHAT in the foot of a 54-year-old male. The tumor pursued a highly aggressive course with rapid regrowth after resection and multiple metastases resulting in patient’s death within 5 months, despite systemic chemotherapy. Immunohistochemistry revealed SMARCA4 loss in the undifferentiated sarcoma, but not in the HFLT/PHAT. Molecular testing confirmed TGFBR3/MGEA5 rearrangements. This report expands the phenotypes of sarcomas developing from pre-existing PHAT/HFLT.
Dissecting whole-brain conduction delays through MRI microstructural measures
Authors: Mancini Matteo , Tian Qiyuan , Fan Qiuyun , Cercignani Mara , Huang Susie Y.
Published: August 2021

Network models based on structural connectivity have been increasingly used as the blueprint for large-scale simulations of the human brain. As the nodes of this network are distributed through the cortex and interconnected by white matter pathways with different characteristics, modeling the associated conduction delays becomes important. The goal of this study is to estimate and characterize these delays directly from the brain structure. To achieve this, we leveraged microstructural measures from a combination of advanced magnetic resonance imaging acquisitions and computed the main determinants of conduction velocity, namely axonal diameter and myelin content. Using the model proposed by Rushton, we used these measures to calculate the conduction velocity and estimated the associated delays using tractography. We observed that both the axonal diameter and conduction velocity distributions presented a rather constant trend across different connection lengths, with resulting delays that scale linearly with the connection length. Relying on insights from graph theory and Kuramoto simulations, our results support the approximation of constant conduction velocity but also show path- and region-specific differences.
Barriers to Trauma Care in South and Central America: a systematic review
Authors: Kinder Florence , Mehmood Sarah , Hodgson Harry , Giannoudis Peter , Howard Anthony
Published: August 2021

Introduction

Trauma is widespread in Central and South America and is a significant cause of morbidity and mortality. Providing high quality emergency trauma care is of great importance. Understanding the barriers to care is challenging; this systematic review aims to establish current the current challenges and barriers in providing high-quality trauma care within the 21 countries in the region.

Methods

OVID Medline, Embase, EBM reviews and Global Health databases were systematically searched in October 2020. Records were screened by two independent researchers. Data were extracted according to a predetermined proforma. Studies of any type, published in the preceding decade were included, excluding grey literature and non-English records. Trauma was defined as blunt or penetrating injury from an external force. Studies were individually critically appraised and assessed for bias using the RTI item bank.

Results

57 records met the inclusion criteria. 20 countries were covered at least once. Nine key barriers were identified: training (37/57), resources and equipment (33/57), protocols (29/57), staffing (17/57), transport and logistics (16/57), finance (15/57), socio-cultural (13/57), capacity (9/57), public education (4/57).

Conclusion

Nine key barriers negatively impact on the provision of high-quality trauma care and highlight potential areas for improving care in Central & South America. Many countries in the region, along with rural areas, are under-represented by the current literature and future research is urgently required to assess barriers to trauma management in these countries.

No funding was received. Clinical Trial Registration: PROSPERO CRD42020220380.
How I do it: proximal control in parkinson’s triangle for a very large paraclinoid aneurysm
Authors: Volovici Victor , Dammers Ruben
Published: August 2021

Background

Paraclinoid aneurysms, especially when they are large, can be quite difficult to treat, both endovascularly and through microsurgical clip reconstruction. There are many possibilities to approach this region surgically, and most hinge on total or partial removal of the anterior clinoid process. Gaining proximal control may be a challenge when space is limited, which is why Parkinson’s triangle may be a viable alternative in some cases.

Methods

We describe in a stepwise fashion the steps used to reconstruct a very large paraclinoid aneurysm. We first attempted to gain proximal control in the carotid cave and later in Parkinson’s triangle because of limited manoeuvrability.

Conclusion

Proximal control in Parkinson’s triangle can be a safe alternative when the post-clinoidal segment of the internal carotid artery (ICA) is short and working space is limited in paraclinoid aneurysm microsurgical clip reconstruction.
Associations between age and cortisol awakening response in patients with borderline personality disorder
Authors: Rausch Juliane , Flach Elisa , Panizza Angelika , Brunner Romuald , Herpertz Sabine C. , Kaess Michael , Bertsch Katja
Published: August 2021

Patients with borderline personality disorder (BPD) often display increased stress vulnerability, which may be linked to altered hypothalamus–pituitary–adrenal (HPA) axis functioning. Corresponding deviations of the cortisol awakening response (CAR) are presumed to mirror maladaptive neuroendocrine processes, which may explain why CARs are increased compared to healthy controls (HC). Prior research speculated that these alterations may be caused by early life stress and/or chronic stress related to the ongoing burden of the disorder. Yet, it remains to be investigated how BPD influences CAR in the course of development. Therefore, the current study examined CAR in female adolescents and adults with BPD compared to HC with a particular focus on associations with age. These potential associations were especially focused, as it was hypothesized that the CAR would be even more elevated (i.e., higher) in older individuals with BPD. CAR was assessed in 54 female individuals with BPD (aged 15–40 years) and 54 sex-, age-, and intelligence-matched HC (aged 15–48 years). Group differences were investigated and analyses of covariance using age as continuous predictor were performed to analyze potential developmental associations with CAR alongside BPD-specific effects. Pearson’s correlations were calculated to examine associations between CAR and age. Analyses were repeated with potential confounders as control factors. Results not only demonstrated increased CARs in female individuals with BPD compared to HC but demonstrated elevated CARs with increasing age in BPD individuals exclusively. Effects remained stable after controlling for potential confounders. Thereby, findings suggest that endocrine alterations in BPD may reinforce with increasing age and BPD chronicity.
Formal requirements modeling for cyber-physical systems engineering: an integrated solution based on FORM-L and Modelica
Authors: Bouskela Daniel , Falcone Alberto , Garro Alfredo , Jardin Audrey , Otter Martin , Thuy Nguyen , Tundis Andrea
Published: August 2021

The increasing complexity of cyber-physical systems (CPSs) makes their design, development and operation extremely challenging. Due to the nature of CPS that involves many heterogeneous components, which are often designed and developed by organizations belonging to different engineering domains, it is difficult to manage, trace and verify their properties, requirements and constraints throughout their lifecycle by using classical techniques. In this context, the paper presents an integrated solution to formally define system requirements and automate their verification through simulation. The solution is based on the FOrmal Requirements Modeling Language and the Modelica language. The solution is exemplified through two case studies concerning a Trailing-Edge High-Lift system and a Heating, Ventilation and Air Conditioning system.
On the manipulability of a class of social choice functions: plurality kth rules
Authors: Bednay Dezső , Tasnádi Attila , Yadav Sonal
Published: August 2021

In this paper we introduce the plurality kth social choice function selecting an alternative, which is ranked kth in the social ranking following the number of top positions of alternatives in the individual ranking of voters. As special case the plurality 1st is the same as the well-known plurality rule. Concerning individual manipulability, we show that the larger k the more preference profiles are individually manipulable. We also provide maximal non-manipulable domains for the plurality kth rules. These results imply analogous statements on the single non-transferable vote rule. We propose a decomposition of social choice functions based on plurality kth rules, which we apply for determining non-manipulable subdomains for arbitrary social choice functions. We further show that with the exception of the plurality rule all other plurality kth rules are group manipulable, i.e. coordinated misrepresentation of individual rankings are beneficial for each group member, with an appropriately selected tie-breaking rule on the set of all profiles.
Is there an imbalance in the supply and demand for universal accessibility knowledge? Twenty years of UAIS papers viewed through the lens of WCAG
Authors: Sandnes Frode Eika
Published: August 2021

Purpose: Some universal accessibility practitioners have voiced that they experience a mismatch in the research focus and the need for knowledge within specialized problem domains. This study thus set out to identify the balance of research into the main areas of accessibility, the impact of this research, and how the research profile varies over time and across geographical regions. Method: All UAIS papers indexed in Scopus were analysed using bibliometric methods. The WCAG taxonomy of accessibility was used for the analysis, namely perceivable, operable, and understandable. Results: The results confirm the expectation that research into visual impairment has received more attention than papers addressing operable and understandable. Although papers focussing on understandable made up the smallest group, papers in this group attracted more citations. Funded research attracted fewer citations than research without funding. The breakdown of research efforts appears consistent over time and across different geographical regions. Researchers in Europe and North America have been active throughout the last two decades, while Southeast Asia, Latin America, and Middle East became active in during the last five years. There is also seemingly a growing trend of out-of-scope papers. Conclusions: Based on the findings, several recommendations are proposed to the UAIS editorial board.
Counteracting flawed landslide data in statistically based landslide susceptibility modelling for very large areas: a national-scale assessment for Austria
Authors: Lima Pedro , Steger Stefan , Glade Thomas
Published: August 2021

The reliability of input data to be used within statistically based landslide susceptibility models usually determines the quality of the resulting maps. For very large territories, landslide susceptibility assessments are commonly built upon spatially incomplete and positionally inaccurate landslide information. The unavailability of flawless input data is contrasted by the need to identify landslide-prone terrain at such spatial scales. Instead of simply ignoring errors in the landslide data, we argue that modellers have to explicitly adopt their modelling design to avoid misleading results. This study examined different modelling strategies to reduce undesirable effects of error-prone landslide inventory data, namely systematic spatial incompleteness and positional inaccuracies. For this purpose, the Austrian territory with its abundant but heterogeneous landslide data was selected as a study site. Conventional modelling practices were compared with alternative modelling designs to elucidate whether an active counterbalancing of flawed landslide information can improve the modelling results. In this context, we compared widely applied logistic regression with an approach that allows minimizing the effects of heterogeneously complete landslide information (i.e. mixed-effects logistic regression). The challenge of positionally inaccurate landslide samples was tackled by elaborating and comparing the models for different terrain representations, namely grid cells, and slope units. The results showed that conventional logistic regression tended to reproduce incompleteness inherent in landslide training data in case the underlying model relied on explanatory variables directly related to the data bias. The adoption of a mixed-effects modelling approach appeared to reduce these undesired effects and led to geomorphologically more coherent spatial predictions. As a consequence of their larger spatial extent, the slope unit–based models were able to better cope with positional inaccuracies of the landslide data compared to their grid-based equals. The presented research demonstrates that in the context of very large area susceptibility modelling (i) ignoring flaws in available landslide data can lead to geomorphically incoherent results despite an apparent high statistical performance and that (ii) landslide data imperfections can actively be diminished by adjusting the research design according to the respective input data imperfections.
Improved PrEP Awareness and Use among Trans Women in San Francisco, California
Authors: Wilson Erin C. , Hernandez Christopher J. , Scheer Susan , Trujillo Dillon , Arayasirikul Sean , Sicro Sofia , McFarland Willi
Published: August 2021

Transgender women face a serious risk of HIV infection. Despite this, there is limited knowledge and use of Pre-exposure prophylaxis (PrEP). We measured the continuity of prevention across services in the PrEP cascade and correlates of PrEP use among trans women in San Francisco enrolled in the 2019/20 National HIV Behavioral Surveillance Study. Knowledge and use of PrEP among trans women in San Francisco increased in recent years; almost all (94.0%) had heard about PrEP, 64.7% had discussed PrEP with a healthcare provider, and 44.8% had taken PrEP in the past 12 months. PrEP use was associated with participation in a PrEP demonstration project (aOR = 31.44, p = 0.001) and condomless receptive anal intercourse (aOR = 3.63, p = 0.024). Injection drug use was negatively associated (aOR = 0.19, p = 0.014). Efforts are needed to combat the gender-based stigma and discrimination faced by trans women, which can result in avoidance and mistrust of the medical system.
Measuring associational thinking through word embeddings
Authors: Periñán-Pascual Carlos
Published: August 2021

The development of a model to quantify semantic similarity and relatedness between words has been the major focus of many studies in various fields, e.g. psychology, linguistics, and natural language processing. Unlike the measures proposed by most previous research, this article is aimed at estimating automatically the strength of associative words that can be semantically related or not. We demonstrate that the performance of the model depends not only on the combination of independently constructed word embeddings (namely, corpus- and network-based embeddings) but also on the way these word vectors interact. The research concludes that the weighted average of the cosine-similarity coefficients derived from independent word embeddings in a double vector space tends to yield high correlations with human judgements. Moreover, we demonstrate that evaluating word associations through a measure that relies on not only the rank ordering of word pairs but also the strength of associations can reveal some findings that go unnoticed by traditional measures such as Spearman’s and Pearson’s correlation coefficients.
A Longitudinal Qualitative Analysis of the Way Peer Support Specialist Roles Change Over Time in a Psychiatric Hospital Setting in Asia
Authors: Poremski Daniel , Kuek Jonathan , Qi Yuan , Li Ziqiang , Yow Kah Lai , Eu Pui Wai , Chua Hong Choon
Published: August 2021

The current study seeks to determine how peer support roles change as peer support specialists’ positions within organizations and departments mature. We followed ten peer support specialists over the course of a year, interviewing them at three points, starting approximately three months after they began working as peer support specialists. We used an inductive process to analyze our data and followed guidelines on the structuring of longitudinal qualitative trajectories to divide the data into watershed moments. Our participants worked in a variety of departments in the hospital, and their service use experiences generally echo those of their service users. Participants appear to pass through four phases over the course of their employment as peers: early beginnings, establishing the role, role narrowing, and role sustainability. Services wishing to integrate new peers must be aware of the time required for integration. Having general job descriptions limited to specifying that peers are expected to use their lived experience to support current service users may lead to uncertainty amongst new and existing staff. Without role clarity, peers may struggle to find their place. Pairing new staff with mentors may limit this burden. As roles consolidate, boundaries may emerge. If these boundaries narrow the role of the PSS, they may no longer find the role appealing. They may then choose other caregiver roles with wider or different spheres of influence. Organizations may benefit by clearly indicating if they expect peer support positions to be static or transitionary.
Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer
Authors: Li Huiping , Song Guohong , Zhou Qiaoxia , Ran Ran , Jiang Hanfang , Zhang Ruyan , Liu Yaxin , Zhang Jiayang , Meng Luping , Ma Liandong , Sun Ye , Wang Meiyu , Zhou Qingqing , Yan Honghua , Zhou Qianxiang , Dong Xunwei , Tong Youzhi
Published: August 2021

Purpose

To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients.

Methods

The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity.

Results

GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing.

Conclusion

GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.
Echocardiography and EuroSCORE II for the stratification of low-gradient severe aortic stenosis and preserved left ventricular ejection fraction
Authors: Fan Yan , Shen Hong , Stacey Brandon , Zhao David , Applegate Robert J. , Kon Neal D. , Kincaid Edward H. , Gandhi Sanjay K. , Pu Min
Published: August 2021

The purpose of this study was to explore the utility of echocardiography and the EuroSCORE II in stratifying patients with low-gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF ≥ 50%) with or without aortic valve intervention (AVI). The study included 323 patients with LG SAS (aortic valve area ≤ 1.0 cm2 and mean pressure gradient < 40 mmHg). Patients were divided into two groups: a high-risk group (EuroSCORE II ≥ 4%, n = 115) and a low-risk group (EuroSCORE II < 4%, n = 208). Echocardiographic and clinical characteristics were analyzed. All-cause mortality was used as a clinical outcome during mean follow-up of 2 ± 1.3 years. Two-year cumulative survival was significantly lower in the high-risk group than the low-risk patients (62.3% vs. 81.7%, p = 0.001). AVI tended to reduce mortality in the high-risk patients (70% vs. 59%; p = 0.065). It did not significantly reduce mortality in the low-risk patients (82.8% with AVI vs. 81.2%, p = 0.68). Multivariable analysis identified heart failure, renal dysfunction and stroke volume index (SVi) as independent predictors for mortality. The study suggested that individualization of AVI based on risk stratification could be considered in a patient with LG SAS and preserved LVEF.
Experiencing the community of inquiry framework using asynchronous online role-playing in computer-aided instruction class
Authors: Junus Kasiyah , Santoso Harry Budi , Ahmad Mubarik
Published: August 2021

This current study investigates the use of online role-playing, in an online discussion forum, in learning the community of inquiry framework – an area of learning covered in the Computer-Aided Instruction (CAI) course, an elective course for Computer Science undergraduate students at Universitas Indonesia. The participants were divided into different roles. Each group was triggered to discuss the implementation of online collaborative learning. A mixed-methods approach was utilised to analyse the qualitative and quantitative data. The result of content analysis exhibited students implementing all the components of the CoI framework. Teaching presence was the rarest, as students were focused on delivering their ideas. Social presence appeared in almost all messages since it is the easiest, and students can feel the impact immediately. The discussion moved to the integration phase but did not proceed to resolution. This study suggested some recommendations and future research topics.
Glycans in autophagy, endocytosis and lysosomal functions
Authors: Reggiori Fulvio , Gabius Hans-Joachim , Aureli Massimo , Römer Winfried , Sonnino Sandro , Eskelinen Eeva-Liisa
Published: August 2021

Glycans have been shown to function as versatile molecular signals in cells. This prompted us to look at their roles in endocytosis, endolysosomal system and autophagy. We start by introducing the cell biological aspects of these pathways, the concept of the sugar code, and provide an overview on the role of glycans in the targeting of lysosomal proteins and in lysosomal functions. Moreover, we review evidence on the regulation of endocytosis and autophagy by glycans. Finally, we discuss the emerging concept that cytosolic exposure of luminal glycans, and their detection by endogenous lectins, provides a mechanism for the surveillance of the integrity of the endolysosomal compartments, and serves their eventual repair or disposal.
Speeding Up Reachability Queries in Public Transport Networks Using Graph Partitioning
Authors: Tesfaye Bezaye , Augsten Nikolaus , Pawlik Mateusz , Böhlen Michael H. , Jensen Christian S.
Published: August 2021

Computing path queries such as the shortest path in public transport networks is challenging because the path costs between nodes change over time. A reachability query from a node at a given start time on such a network retrieves all points of interest (POIs) that are reachable within a given cost budget. Reachability queries are essential building blocks in many applications, for example, group recommendations, ranking spatial queries, or geomarketing. We propose an efficient solution for reachability queries in public transport networks. Currently, there are two options to solve reachability queries. (1) Execute a modified version of Dijkstra’s algorithm that supports time-dependent edge traversal costs; this solution is slow since it must expand edge by edge and does not use an index. (2) Issue a separate path query for each single POI, i.e., a single reachability query requires answering many path queries. None of these solutions scales to large networks with many POIs. We propose a novel and lightweight reachability index. The key idea is to partition the network into cells. Then, in contrast to other approaches, we expand the network cell by cell. Empirical evaluations on synthetic and real-world networks confirm the efficiency and the effectiveness of our index-based reachability query solution.
Metabolic response of Botryococcus braunii to high bicarbonate dosages and other conditions: analysis of photosynthetic performance, productivity, and lipidomic profile
Authors: Giraldo Néstor David , Correa Sandra Marcela , Arbeláez Andrés , Figueroa Felix L. , Ríos-Estepa Rigoberto , Atehortúa Lucía
Published: August 2021

In this study the metabolic responses of Botryococcus braunii were analyzed upon different inorganic carbon dosages and nutrient limitation conditions in terms of lipid and biomass productivity, as well as photosynthetic performance. The nutritional schemes evaluated included different levels of sodium bicarbonate and nitrogen and phosphorus starvation, which were contrasted against standard cultures fed with CO2. Bicarbonate was found to be an advantageous carbon source since high dosages caused a significant increase in biomass and lipid productivity, in addition to an enhanced photosynthetic quantum yield and neutral lipids abundance. This contrasts to the commonly used approach of microalgae nutrient limitation, which leads to high lipid accumulation at the expense of impaired cellular growth, causing a decline in overall lipid productivity. The lipidome analysis served to hypothesize about the influence of the nutritional context on B. braunii structural and storage lipid metabolism, besides the adaptive responses exhibited by cells that underwent nutrient stress.
Effect of dramatic alteration of landscape structure on the Orthoptera assemblages of Transcarpathian lowland meadows (West Ukraine)
Authors: Szanyi Sz. , Potish L. , Rácz I. A. , Varga Z. , Nagy A.
Published: August 2021

Traditional and extensively used agricultural lands maintain and protect high levels of biological diversity. This diversity is in decline due to land use intensification and abandonment. Natural and semi-natural grasslands of the Carpathian lowlands have become endangered over the 19th century. However, some remains of former wetlands have survived land use change in the Bereg Region (North-eastern Hungary and Eastern Ukraine). We surveyed Orthopterans as sensitive indicators of habitat structure and microclimate in grasslands. We identified three different Orthoptera assemblages and their character species. Although rare and especially valuable species were not found in the studied sites, the species rich remains of wetlands still protected relics of former wildlife of wetlands. Understanding the quantitative character of the assemblages, ratios of life forms and particularly co-occurrences of their character species (Chorthippus dorsatus, Leptophyes albovittata, Tettigonia viridissimaandRuspolia nitidula) and use of Grasshopper Conservation Indexes (GCI) can help to identify remaining good quality patches with highest conservation value and monitoring.

Implications for insect conservation

The focused management of these habitats with reconsideration of the traditional water management can be effective practice for wetland management and Orthoptera conservation.
Development of bioinks for 3D printing microporous, sintered calcium phosphate scaffolds
Authors: Montelongo Sergio A. , Chiou Gennifer , Ong Joo L. , Bizios Rena , Guda Teja
Published: August 2021

Beta-tricalcium phosphate (β-TCP)-based bioinks were developed to support direct-ink 3D printing-based manufacturing of macroporous scaffolds. Binding of the gelatin:β-TCP ink compositions was optimized by adding carboxymethylcellulose (CMC) to maximize the β-TCP content while maintaining printability. Post-sintering, the gelatin:β-TCP:CMC inks resulted in uniform grain size, uniform shrinkage of the printed structure, and included microporosity within the ceramic. The mechanical properties of the inks improved with increasing β-TCP content. The gelatin:β-TCP:CMC ink (25:75 gelatin:β-TCP and 3% CMC) optimized for mechanical strength was used to 3D print several architectures of macroporous scaffolds by varying the print nozzle tip diameter and pore spacing during the 3D printing process (compressive strength of 13.1 ± 2.51 MPa and elastic modulus of 696 ± 108 MPa was achieved). The sintered, macroporous β-TCP scaffolds demonstrated both high porosity and pore size but retained mechanical strength and stiffness compared to macroporous, calcium phosphate ceramic scaffolds manufactured using alternative methods. The high interconnected porosity (45–60%) and fluid conductance (between 1.04 ×10−9 and 2.27 × 10−9 m4s/kg) of the β-TCP scaffolds tested, and the ability to finely tune the architecture using 3D printing, resulted in the development of novel bioink formulations and made available a versatile manufacturing process with broad applicability in producing substrates suitable for biomedical applications.
Genetic Analysis of a Cohort of 275 Patients with Hyper-IgE Syndromes and/or Chronic Mucocutaneous Candidiasis
Authors: Frede Natalie , Rojas-Restrepo Jessica , Caballero Garcia de Oteyza Andrés , Buchta Mary , Hübscher Katrin , Gámez-Díaz Laura , Proietti Michele , Saghafi Shiva , Chavoshzadeh Zahra , Soler-Palacin Pere , Galal Nermeen , Adeli Mehdi , Aldave-Becerra Juan Carlos , Al-Ddafari Moudjahed Saleh , Ardenyz Ömür , Atkinson T. Prescott , Kut Fulya Bektas , Çelmeli Fatih , Rees Helen , Kilic Sara S. , Kirovski Ilija , Klein Christoph , Kobbe Robin , Korganow Anne-Sophie , Lilic Desa , Lunt Peter , Makwana Niten , Metin Ayse , Özgür Tuba Turul , Karakas Ayse Akman , Seneviratne Suranjith , Sherkat Roya , Sousa Ana Berta , Unal Ekrem , Patiroglu Turkan , Wahn Volker , von Bernuth Horst , Whiteford Margo , Doffinger Rainer , Jouhadi Zineb , Grimbacher Bodo
Published: August 2021

Hyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers.
Control on the Manifolds of Mappings with a View to the Deep Learning
Authors: Agrachev Andrei , Sarychev Andrey
Published: August 2021

Deep learning of the artificial neural networks (ANN) can be treated as a particular class of interpolation problems. The goal is to find a neural network whose input-output map approximates well the desired map on a finite or an infinite training set. Our idea consists of taking as an approximant the input-output map, which arises from a nonlinear continuous-time control system. In the limit such control system can be seen as a network with a continuum of layers, each one labelled by the time variable. The values of the controls at each instant of time are the parameters of the layer.
Elder Mistreatment Victims during the COVID-19 Pandemic: Administrative Data from San Francisco Adult Protective Services
Authors: Liu Pi-Ju , Wang Aining , Schwab-Reese Laura M. , Stratton Sara K.
Published: August 2021

This study examined elder mistreatment victims’ experiences at the beginning of the COVID-19 pandemic, focusing on their COVID-19 awareness and unmet needs. San Francisco Adult Protective Services (APS) caseworkers conducted phone interviews with clients or collaterals (client’s family, trusted other, or service provider) to inquire about clients’ awareness of COVID-19 and unmet needs. Nine-hundred-and-thirty-four (71%) of 1,313 APS’ past clients or their collaterals were interviewed, with 741 (79%) responding positively to COVID-19-awareness questions, and 697 (75%) having no unmet needs. Binary logistic regression with Firth adjusted maximum likelihood estimation method revealed that older persons (p < .05), self-neglectors (p < .05), and victims of neglect (p < .05) were less aware of COVID-19. Unmet needs varied by mistreatment type. Victims of isolation were more likely to have medical needs (p < .05), while victims of emotional abuse were more likely to report loneliness (p < .001). Case notes reflected clients who were well-prepared for the pandemic, versus those who required additional assistance to follow preventative measures of the COVID-19 pandemic to stay home. Although the majority of San Francisco APS’ past clients experienced no unmet needs at the beginning of the COVID-19 pandemic, the prolonged length and intensity of the pandemic could have exacerbated this vulnerable group’s situation. Collaboration between service providers is key in assisting victims experiencing unmet needs to live safely in a public health crisis, especially underserved victims of specific ethnic backgrounds.
Anti-fog nanocomposite coatings of enhanced durability
Authors: Momoli Riccardo , Giacomazzo Sujatha , Gandin Alessandro , Brusatin Giovanna
Published: August 2021

Highly porous nanocomposite films were produced at room temperature from SiO2 or TiO2–SiO2 solutions synthesized by a sol–gel route in the presence of oxide nanoparticles. The photocatalytic behavior of titania-based films was controlled at the sol synthesis step, through three parameters: the relative molar concentration between polymeric and condensed silica, the reactivity of the hydrolysis step, and the relative molar concentration of the active component. The reported method allowed ample tuneability of film refractive index, an important parameter for the design of antireflective and multifunctional coatings. Superhydrophilic properties were demonstrated by the samples and, notably, retained for over 30 days. Experimentally mimicking accelerated surface pollution with olive oil and stearic acid, a strong correlation was found between residual organic contamination, quantified by integrating the film absorption FT-IR spectrum over the C–Hn stretching area, and the measured water contact angle (WCA). Strategies for a fast surface cleaning and restoration of the superhydrophilic behavior via a mild oxidizing agent, based on UV exposure or immersion in a NaClO water solution, were investigated.
Long-term maize-Desmodium intercropping shifts structure and composition of soil microbiome with stronger impact on fungal communities
Authors: Mwakilili Aneth David , Mwaikono Kilaza Samson , Herrera Sebastian Larsson , Midega Charles A. O. , Magingo Francis , Alsanius Beatrix , Dekker Teun , Lyantagaye Sylvester Leonard
Published: August 2021

Purpose

Push–pull is an intercropping technology that is rapidly spreading among smallholder farmers in Sub-Saharan Africa. The technology intercrops cereals with Desmodium to fight off stem borers, eliminate parasitic weeds, and improve soil fertility and yields of cereals. The above-ground components of push–pull cropping have been well investigated. However, the impact of the technology on the soil microbiome and the subsequent role of the microbiome on diverse ecosystem benefits are unknown. Here we describe the soil microbiome associated with maize—Desmodium intercropping in push–pull farming in comparison to long-term maize monoculture.

Methods

Soil samples were collected from long-term maize—Desmodium intercropping and maize monoculture plots at the international centre for insect physiology and ecology (ICIPE), Mbita, Kenya. Total DNA was extracted before16S rDNA and ITS sequencing and subsequent analysis on QIIME2 and R.

Results

Maize—Desmodium intercropping caused a strong divergence in the fungal microbiome, which was more diverse and species rich than monoculture plots. Fungal groups enriched in intercropping plots are linked to important ecosystem services, belonging to functional groups such as mycorrhiza, endophytes, saprophytes, decomposers and bioprotective fungi. Fewer fungal genera were enriched in monoculture plots, some of which were associated with plant pathogenesis and opportunistic infection in humans. In contrast, the impact of intercropping on soil bacterial communities was weak with few differences between intercropping and monoculture.

Conclusion

Maize—Desmodium intercropping diversifies fungal microbiomes and favors taxa associated with important ecosystem services including plant health, productivity and food safety.