bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research and Education Needs for Complex Generics
Authors: Stern Sydney , Coghlan Jill , Krishnan Vishalakshi , Raney Sam G. , Babiskin Andrew , Jiang Wenlei , Lionberger Robert , Xu Xiaoming , Schwendeman Anna , Polli James E. 
Published: December 2021

AbstractComplex generics are generic versions of drug products that generally have complex active ingredients, complex formulations, complex routes of delivery, complex dosage forms, are complex drug-device combination products, or have other characteristics that can make it complex to demonstrate bioequivalence or to develop as generics. These complex products (i.e. complex generics) are an important element of the United States (U.S.) Food and Drug Administration’s (FDA’s) Generic Drug User Fee Amendments (GDUFA) II Commitment Letter. The Center for Research on Complex Generics (CRCG) was formed by a grant from the FDA to address challenges associated with the development of complex generics. To understand these challenges, the CRCG conducted a “Survey of Scientific Challenges in the Development of Complex Generics”. The three main areas of questioning were directed toward which (types of) complex products, which methods of analysis to support a demonstration of bioequivalence, and which educational topics the CRCG should prioritize. The survey was open to the public on a website maintained by the CRCG. Regarding complex products, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and inhalation and nasal products. Regarding methods of analysis, the top three selections were locally-acting physiologically-based pharmacokinetic modeling; oral absorption models and bioequivalence; and data analytics and machine learning. Regarding educational topics, the top three selections were complex injectables, formulations, and nanomaterials; drug-device combination products; and data analytics, including quantitative methods and modeling & simulation. These survey results will help prioritize the CRCG’s initial research and educational initiatives.
Oddlab: fault-tolerant aware load-balancing framework for data center networks
Authors: Alawadi Aymen Hasan , Molnár Sándor 
Published: December 2021

AbstractData center networks (DCNs) act as critical infrastructures for emerging technologies. In general, a DCN involves a multi-rooted tree with various shortest paths of equal length from end to end. The DCN fabric must be maintained and monitored to guarantee high availability and better QoS. Traditional traffic engineering (TE) methods frequently reroute large flows based on the shortest and least-congested paths to maintain high service availability. This procedure results in a weak link utilization with frequent packet reordering. Moreover, DCN link failures are typical problems. State-of-the-art approaches address such challenges by modifying the network components (switches or hosts) to discover and avoid broken connections. This study proposes Oddlab (Odds labels), a novel deployable TE method to guarantee the QoS of multi-rooted data center (DC) traffic in symmetric and asymmetric modes. Oddlab creatively builds a heuristic model for efficient flow scheduling and faulty link detection by exclusively using the gathered statistics from the DCN data plane, such as residual bandwidth and the number of installed elephant flows. Besides, the proposed method is implemented in an SDN-based DCN without altering the network components. Our findings indicate that Oddlab can minimize the flow completion time, maximize bisection bandwidth, improve network utilization, and recognize faulty links with sufficient accuracy to improve DC productivity.
FertilityOnline: A Straightforward Pipeline for Functional Gene Annotation and Disease Mutation Discovery
Authors: Gao Jianing , Zhang Huan , Jiang Xiaohua , Ali Asim , Zhao Daren , Bao Jianqiang , Jiang Long , Iqbal Furhan , Shi Qinghua , Zhang Yuanwei 
Published: December 2021

AbstractExploring the genetic basis of human infertility is currently under intensive investigation. However, only a handful of genes have been validated in animal models as disease-causing genes in infertile men. Thus, to better understand the genetic basis of human spermatogenesis and bridge the knowledge gap between humans and other animal species, we construct the FertilityOnline, a database integrating the literature-curated functional genes during spermatogenesis into an existing spermatogenic database, SpermatogenesisOnline 1.0. Additional features, including the functional annotation and genetic variants of human genes, are also incorporated into FertilityOnline. By searching this database, users can browse the functional genes involved in spermatogenesis and instantly narrow down the number of candidates of genetic mutations underlying male infertility in a user-friendly web interface. Clinical application of this database was exampled by the identification of novel causative mutations in synaptonemal complex central element protein 1 (SYCE1) and stromal antigen 3 (STAG3) in azoospermic men. In conclusion, FertilityOnline is not only an integrated resource for spermatogenic genes but also a useful tool facilitating the exploration of the genetic basis of male infertility. FertilityOnline can be freely accessed at http://mcg.ustc.edu.cn/bsc/spermgenes2.0/index.html.
Search and Rescue in the Pacific West States
Authors: Ettinger Stephen , Long Andrea , Ganti Arun , Mortimer Roger B. , Chiang William , Spano Susanne 
Published: December 2021

Introduction The training practices and the level of medical oversight of search and rescue (SAR) organizations in the US National Park Service (NPS) Pacific west region is not known. Methods A database of SAR teams in the NPS Pacific west region was assembled using public sources. SAR team leaders received an electronic survey between May and December 2019. A descriptive analysis characterizing team size, technical and medical training protocols, and medical oversight was completed. Results are reported as median (interquartile range, range). Results Of the 250 SAR teams contacted, 39% (n=97) completed our survey. Annual mission volume was 25 (10–50, 1–200). Team size was 30 members (22–58, 1–405). SAR teams most frequently trained in helicopter operations (77%), low-angle rope rescue (75%), and avalanche rescue (43%). Nearly all teams (99%) had members with some medical training: first aid or cardiopulmonary resuscitation (89%), emergency medical technicians (75%), registered nurses or midlevel providers (52%), and physicians (40%). SAR members administered field medical care (84%), often in coordination with EMS (77%). Medical direction was present on a minority of teams (45%), most frequently by a provider specialized in emergency medicine (68%). Expanded medical procedures were permitted on 21% of SAR teams. Conclusions SAR teams across the NPS Pacific west region had composition and training standards similar to those surveyed previously in the US intermountain states. Healthcare professionals were present on most teams, typically as team members, not as medical directors. Few SAR teams use medical protocols in remote care environments.
Geodetic Monitoring at Axial Seamount Since Its 2015 Eruption Reveals a Waning Magma Supply and Tightly Linked Rates of Deformation and Seismicity
Authors: Chadwick William W. , Wilcock William S. D. , Nooner Scott L. , Beeson Jeffrey W. , Sawyer Audra M. , Lau T.‐K. 
Published: December 2021

AbstractAxial Seamount is a basaltic hot spot volcano with a summit caldera at a depth of ∼1,500 m below sea level, superimposed on the Juan de Fuca spreading ridge, giving it a robust and continuous magma supply. Axial erupted in 1998, 2011, and 2015, and is monitored by a cabled network of instruments including bottom pressure recorders and seismometers. Since its last eruption, Axial has re‐inflated to 85%–90% of its pre‐eruption level. During that time, we have identified eight discrete, short‐term deflation events of 1–4 cm over 1–3 weeks that occurred quasi‐periodically, about every 4–6 months between August 2016 and May 2019. During each short‐term deflation event, the rate of earthquakes dropped abruptly to low levels, and then did not return to higher levels until reinflation had resumed and returned near its previous high. The long‐term geodetic monitoring record suggests that the rate of magma supply has varied by an order of magnitude over decadal time scales. There was a surge in magma supply between 2011 and 2015, causing those two eruptions to be closely spaced in time and the supply rate has been waning since then. This waning supply has implications for eruption forecasting and the next eruption at Axial still appears to be 4–9 years away. We also show that the number of earthquakes per unit of uplift has increased exponentially with total uplift since the 2015 eruption, a pattern consistent with a mechanical model of cumulative rock damage leading to bulk failure during magma accumulation between eruptions.
3‐D Crustal Azimuthal Anisotropy Reveals Multi‐Stage Deformation Processes of the Sichuan Basin and Its Adjacent Area, SW China
Authors: Zhang Zhiqi , Yao Huajian , Wang Weitao , Liu Chuangming 
Published: December 2021

AbstractThe collision of the South China Block and the North China Block and the eastward extrusion of the Tibetan Plateau materials have caused complicated tectonic deformation and strong seismicity around the Sichuan Basin (SCB). In order to reveal regional stress distribution and deformation mechanisms, we invert for a 3‐D high‐resolution shear wave velocity and azimuthal anisotropy model from ambient noise tomography with data from 483 broadband seismographs deployed around the SCB. Our results reveal strong lateral contrasts of azimuthal anisotropy in the crust. The western Sichuan depression shows weak deformation. The central Sichuan uplift, used to be a stable microcontinent, shows relatively strong and coherent fossil anisotropy. In contrast, the eastern Sichuan folds shows strong anisotropy, indicating intense regional deformation. The fast axis direction is bifurcated when reaching the Longmenshan fault, which indicates the obstruction of the SCB to the crustal low velocity materials beneath the Songpan‐Ganzi Block. In the east, the rigid SCB and strike‐slip faults may transform the compressive stress to shear deformation in adjacent areas and cause a ring‐shaped anisotropy pattern below 15 km depth. Furthermore, anisotropy patterns display strong contrast at shallow depths in the Weiyuan and Changning regions, which may facilitate the accumulation of strain and more likely induce earthquakes during the shale gas exploration stage. Our new model provides important constraints for understanding the multi‐stage deformation processes in and around the SCB.
Characterizing the Roles of Biogeochemical Cycling and Ocean Circulation in Regulating Marine Copper Distributions
Authors: Cui Minming , Gnanadesikan Anand 
Published: December 2021

AbstractCopper (Cu) is a key micronutrient for marine phytoplankton. Its oceanic biogeochemical cycle has elicited considerable attention due to dissolved Cu exhibiting a unique linear profile with depth. Several processes have been proposed for explaining this behavior. In this study, we characterize the relationships between the observed Cu, PO43−, and Si on a global scale. We find that the depth profiles of Cu resemble those of Si more than of PO43− in the global ocean. To understand their relationships, we couple the biogeochemical and internal circulation processes in a model, fitting optimal Cu:PO43− uptake ratios and remineralization length‐scales to replicate the marine Cu distributions. The modeling results suggest that Cu uptake needs in the Southern Ocean are substantially higher than those in other oceanic regions. In addition, our modeling results indicate a deep Cu remineralization in the global ocean. We offer an alternative mechanism that relies on biogeochemical cycling and internal circulation to produce the linear depth profiles of dissolved Cu. Our results suggest that diatoms are likely the major phytoplankton dominating oceanic Cu cycling.
Central Continental Boreal Summer “Warming Holes” Modulated by Atlantic Multidecadal Oscillation Via Low‐Level Jets
Authors: Pan Zaitao , Kumar Sanjiv , Zhang Yuanjie , Shi Chunhua 
Published: December 2021

AbstractDespite the accelerated global warming, the central‐eastern U.S. experienced summer daytime cooling during the 20th century. A number of studies have attributed various factors responsible for this abnormal regional cooling, termed the “warming hole (WH)”. This study demonstrates that another WH also existed in the south‐central China that shares similar temporal trend and geographical location to the U.S. WH, including the cooling reversal around 1995. Generalizing the two WHs unravels that they both occurred (a) to the east of major mountain ranges, (b) in heavily cultivated agricultural regions, and (c) near the terminus of the low‐level jets. This study further finds that the WH patterns are the leading mode of surface maximum temperature variability in summer of their respective regions. The WH cooling was consistent with reduction in cloud‐forced solar radiation supported by moisture convergence through weakening of low‐level southerly flow downstream of China WH and strengthening of the southerly flow upstream of U.S. WH. The long‐term trends of WH temperature are highly correlated to the Atlantic Multidecadal Oscillation (AMO) and WH cooling turned into warming around 1995 when the AMO shifted to the positive phase, which combined with overall regional warming, may explain why the summer WH phenomenon has been in diminution for past two decades or so. Given the AMO's association with global climate trend, the WH phenomenon could also be viewed as a local thermal response to the global warming via AMO modulation of regional dynamic and moisture circulation.
Determining Spatial Scales of Soil Moisture—Cloud Coupling Pathways Using Semi‐Idealized Simulations
Authors: Sakaguchi K. , Berg L. K. , Chen J. , Fast J. , Newsom R. , Tai S.‐L. , Yang Z. , Gustafson W. I. , Gaudet B. J. , Huang M. , Pekour M. , Pressel K. , Xiao H. 
Published: December 2021

AbstractThe spatial scales of land‐atmosphere interactions over heterogeneous, realistic soil moisture patterns are critical to improve our understanding of land‐atmosphere interactions. However, these scales are poorly quantified. We use high‐resolution numerical experiments to quantify the spatial scales for a selected day during the Holistic Interactions of Shallow Clouds, Aerosols, and Land‐Ecosystems (HI‐SCALE) campaign in Oklahoma. A semi‐idealized approach (removing background winds and surface topography while retaining the real‐world data for other boundary conditions) enables examination of the local influence from the surface. Simulations that apply uniform surface, variable land cover with uniform soil moisture, and variable land cover with variable soil moisture are then compared. Land cover variations, especially water and urban surfaces, create two variance peaks in the surface sensible heat flux in the scales >10 km (meso‐β) and <6 km (meso‐γ). Both peaks are enhanced by the observation‐based soil moisture distribution that has most of its variance in the meso‐β scale. Atmospheric response in the meso‐β scale is hydrostatic with weak vertical motion. The land cover variations induce secondary circulations in the scales of 2.5–6 km. The additional soil moisture variability intensifies extreme circulations over dry soil patches and sharp sensible heat flux gradients, slightly extending the characteristic scales to 2.5–9 km. While their areal coverage is small, soil moisture variations on such “hotspots” lead to substantially larger convective cloud structure and domain‐mean rainfall, calling for a consideration of their non‐linear effect in large‐scale models.
Airborne Measurements of Surface Albedo and Leaf Area Index of Snow‐Covered Boreal Forest
Authors: Manninen Terhikki , Roujean Jean‐Louis , Hautecoeur Olivier , Riihelä Aku , Lahtinen Panu , Jääskeläinen Emmihenna , Siljamo Niilo , Anttila Kati , Sukuvaara Timo , Korhonen Lauri 
Published: December 2021

AbstractHelicopter based simultaneous measurements of broadband surface albedo and the effective leaf area index (LAIeff) were carried out in subarctic area of Finnish Lapland in spring 2008, 2009, and 2010 under varying illumination and snow cover conditions. Vertical profile measurements show that the found relationship between albedo and LAIeff seems to be rather independent of the flight altitude and therefore the footprint scale. Actually, flights above 500 m in altitude revealed low variations of the surface albedo approaching an aerial average at 1 km, meaning that a footprint of 20 km is representative of the landscape. The albedo of the area was beta distributed, and without LAIeff values below 0.25, the average albedo value of the area would decrease from 0.49 to 0.44 showing the albedo sensitivity to sparse vegetation. The results agreed with the photon recollision probability based model PARAS and the MODIS satellite albedo product MCD43A3. However, differences between satellite based and airborne albedo values were noticed, which could be explained by a difference in footprint size and/or the strong local heterogeneity as certain flights were operated on specific targets.
Influence of stress induced by the first announced state of emergency due to coronavirus disease 2019 on outpatient blood pressure management in Japan
Authors: Kobayashi Kazuo , Chin Keiichi , Umezawa Shinichi , Ito Shun , Yamamoto Hareaki , Nakano Shiro , Takada Nobukazu , Hatori Nobuo , Tamura Kouichi 
Published: December 2021

AbstractTo prevent further spread of coronavirus disease 2019 (COVID-19), the Japanese government announced a state of emergency, resulting in major stress for the population. The aim of this study was to investigate a possible association between changes in daily stress and blood pressure (BP) in Japanese patients. We retrospectively investigated 748 patients with chronic disease who were treated by the Sagamihara Physicians Association to determine changes in stress during the COVID-19 state of emergency from 7 April to 31 May 2020. During the state of emergency, office BP significantly increased from 136.5 ± 17.5/78.2 ± 12.0 to 138.6 ± 18.6/79.0 ± 12.2 (p < 0.001 and p = 0.03, respectively). In contrast, home BP significantly decreased from 128.2 ± 10.3/75.8 ± 8.8 to 126.9 ± 10.2/75.2 ± 9.0 (p < 0.001 and p = 0.01, respectively), and the ratio of white coat hypertension was significantly increased (p < 0.001). Fifty-eight percent of patients worried about adverse effects of hypertension as a condition contributing to the severity and poor prognosis of COVID-19; decreased amounts of exercise and worsened diet compositions were observed in 39% and 17% of patients, respectively. In conclusion, a significant increase in office BP with the white coat phenomenon was observed during the state of emergency, as well as an increase in related stress. To prevent cardiovascular events, general practitioners should pay more attention to BP management during stressful global events, including the COVID-19 pandemic.
mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses
Authors: Huynh HoangDinh , Levitz Ruth , Huang Rong , Kahn Jeffrey S. 
Published: December 2021

AbstractTherapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.
Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia
Authors: Sabaie Hani , Moghaddam Madiheh Mazaheri , Moghaddam Marziyeh Mazaheri , Ahangar Noora Karim , Asadi Mohammad Reza , Hussen Bashdar Mahmud , Taheri Mohammad , Rezazadeh Maryam 
Published: December 2021

AbstractSchizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein–protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.