bluuebunny/crossref_metadata_2025 huggingface dataset:
Eemian landscape response to climatic shifts and evidence for northerly Neanderthal occupation at a palaeolake margin in northern Germany
Authors: Hein Michael , Urban Brigitte , Tanner David Colin , Buness Anton Hermann , Tucci Mario , Hoelzmann Philipp , Dietel Sabine , Kaniecki Marie , Schultz Jonathan , Kasper Thomas , von Suchodoletz Hans , Schwalb Antje , Weiss Marcel , Lauer Tobias
Published: August 2021

The prevailing view suggests that the Eemian interglacial on the European Plain was characterized by largely negligible geomorphic activity beyond the coastal areas. However, systematic geomorphological studies are sparse. Here we present a detailed reconstruction of Eemian to Early Weichselian landscape evolution in the vicinity of a small fingerlake on the northern margin of the Salzwedel Palaeolake in Lower Saxony (Germany). We apply a combination of seismics, sediment coring, pollen analysis and luminescence dating on a complex sequence of colluvial, paludal and lacustrine sediments. Results suggest two pronounced phases of geomorphic activity, directly before the onset and at the end of the Eemian period, with an intermediate period of pronounced landscape stability. The dynamic phases were largely driven by incomplete vegetation cover, but likely accentuated by fluvial incision in the neighbouring Elbe Valley. Furthermore, we discovered Neanderthal occupation at the lakeshore during Eemian pollen zone (PZ) E IV, which is chronologically in line with other known Eemian sites of central Europe. Our highly‐resolved spatio‐temporal data substantially contribute to the understanding of climate‐induced geomorphic processes throughout and directly after the last interglacial period. It helps unraveling the landscape dynamics between the coastal areas to the north and the loess belt to the south.
Monitoring of Environmental Contaminants in Mixed-Use Watersheds Combining Targeted and Nontargeted Analysis with Passive Sampling
Authors: Renaud Justin B. , Sabourin Lyne , Hoogstra Shawn , Helm Paul , Lapen David R. , Sumarah Mark W.
Published: August 2021

Understanding the environmental fate, transport, and occurrence of pesticides and pharmaceuticals in aquatic environments is of utmost concern to regulators. Traditionally, monitoring of environmental contaminants in surface water has consisted of liquid chromatography–tandem mass spectrometry analyses for a set of targeted compounds in discrete samples. These targeted approaches are limited by the fact that they only provide information on compounds within a target list present at the time and location of sampling. To address these limitations, there has been considerable interest in suspect screening and nontargeted analysis (NTA), which allow for the detection of all ionizable compounds in the sample with the added benefit of data archiving for retrospective mining. Even though NTA can detect a large number of contaminants, discrete samples only provide a snapshot perspective of the chemical disposition of an aquatic environment at the time of sampling, potentially missing episodic events. We evaluated two types of passive chemical samplers for nontargeted analysis in mixed-use watersheds. Nontargeted data were processed using MS-DIAL to screen against our in-house library and public databases of more than 1300 compounds. The data showed that polar organic chemicals integrative samplers (POCIS) were able to capture the largest number of analytes with better reproducibility than organic compound–diffusive gradients in thin film (o-DGT), resulting from the greater amount of binding sorbent. We also showed that NTA combined with passive sampling gives a more representative picture of the contaminants present at a given site and enhances the ability to identify the nature of point and nonpoint pollution sources and ecotoxicological impacts. Environ Toxicol Chem 2022;41:1131–1143. © 2021 Her Majesty the Queen in Right of Canada Environmental Toxicology and Chemistry © 2021 SETAC. Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

Abstract

Environmental surface water was collected by discrete sampling and two types of passive chemical samplers; organic compound–diffusive gradients in thin film (o–DGT) and polar organic chemicals integrative samplers (POCIS). Samples were analyzed by targeted and nontargeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) for determination of pesticide and pharmaceutical contaminants in surface water. QQQ = triple quadrupole mass spectrometer; NTA = nontargeted analysis.
Aquatic Biofilms—Sink or Source of Microplastics? A Critical Reflection on Current Knowledge
Authors: Kalčíková Gabriela , Bundschuh Mirco
Published: August 2021

The scientific understanding regarding sources, occurrence, and effects of microplastics in the aquatic environment has advanced rapidly, leaving some meaningful knowledge gaps virtually untouched. One of them is the interactions of microplastics and biofilms, microbial communities ubiquitous in aquatic ecosystems and fundamental for a range of ecosystem-level processes. It is evident that biofilms can quickly develop on the microplastic surface and consequently change particle properties and, as such, its fate and ecotoxicity. Moreover, microplastics interact with ubiquitous biofilms that are developed on any surfaces in aquatic ecosystems. Although the knowledge about these interactions is at best limited, it is expected that microplastics attach to the water–biofilm interface or penetrate the biofilm matrix. Microplastics can accumulate and ab- or adsorb to those biofilms where they are subjected to transformation processes such as fragmentation. Thus, biofilms may function as a sink. Changes in environmental conditions may, however, stress biofilms initiating their dieback and microplastic release, which could turn biofilms into a source of microplastics. We argue that the accumulation and release dynamics are a largely overlooked but potentially important piece to the puzzle that is a comprehensive understanding of microplastic fate in the environment and thus under the influence of multiple interacting factors. Environ Toxicol Chem 2022;41:838–843. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
A Comparison of Spoken and Written Language Use in Traditional andTechnology‐MediatedLearning Environments
Authors: Kyle Kristopher , Choe Ann Tai , Eguchi Masaki , LaFlair Geoff , Ziegler Nicole
Published: August 2021

A key piece of a validity argument for a language assessment tool is clear overlap between assessment tasks and the target language use (TLU) domain (i.e., the domain description inference). The TOEFL 2000 Spoken and Written Academic Language (T2K‐SWAL) corpus, which represents a variety of academic registers and disciplines in traditional learning environments (e.g., lectures, office hours, textbooks, course packs), has served as an important foundation for theTOEFL iBT® test's domain description inference for more than 15 years. There are, however, signs that the characteristics of the registers that students encounter may be changing. Increasingly, typical university courses include technology‐mediated learning environments (TMLEs), such as those represented by course management software and other online educational tools. To ensure that the characteristics of TOEFL iBT test tasks continue to align with the TLU domain, it is important to analyze the registers that are typically encountered in TMLEs. In this study, we address this issue by collecting a relatively large (4.5 million words) corpus of spoken and written TMLE registers across the six primary disciplines represented in T2K‐SWAL. This corpus was subsequently tagged for a wide variety of linguistic features, and a multidimensional analysis was conducted to compare and contrast written and spoken language in TMLE and T2K‐SWAL. The results indicate that although some similarities exist across spoken and written texts in traditional learning environments and TMLEs, language use also differs across learning environments (and modes) with regard to key linguistic dimensions.
The real effect of foreign exchange hedging on corporate innovation
Authors: Xia Chongwu , Yang Chuyi , Zhang Lei
Published: August 2021

We study the effects of foreign exchange hedging on corporate innovation. According to the information asymmetry hypothesis, corporate hedging reduces firms' information asymmetry, alleviates managers' career concerns, and helps investors better monitor managers, which enhances innovation. According to the market pressure hypothesis, hedging imposes short‐term earnings pressure on managers as a result of mark‐to‐market hedge accounting, discouraging innovation. Using 32,194 observations of 5847 nonfinancial firms from 1998 to 2006, we document results that support the information asymmetry hypothesis. Hedged firms invest more heavily in innovative projects, generate more patents, and have more patent citations. To address endogeneity concerns, we employ both difference‐in‐differences and instrumental variable regressions and explicitly test for reverse causality.
Assessing acute myeloid leukemia susceptibility in rearrangement‐driven patients by DNA breakage at topoisomerase II and CCCTC‐binding factor/cohesin binding sites
Authors: Atkin Naomi D. , Raimer Heather M. , Wang Zhenjia , Zang Chongzhi , Wang Yuh‐Hwa
Published: August 2021

An initiating DNA double strand break (DSB) event precedes the formation of cancer‐driven chromosomal abnormalities, such as gene rearrangements. Therefore, measuring DNA breaks at rearrangement‐participating regions can provide a unique tool to identify and characterize susceptible individuals. Here, we developed a highly sensitive and low‐input DNA break mapping method, the first of its kind for patient samples. We then measured genome‐wide DNA breakage in normal cells of acute myeloid leukemia (AML) patients with KMT2A (previously MLL) rearrangements, compared to that of nonfusion AML individuals, as a means to evaluate individual susceptibility to gene rearrangements. DNA breakage at the KMT2A gene region was significantly greater in fusion‐driven remission individuals, as compared to nonfusion individuals. Moreover, we identified select topoisomerase II (TOP2)‐sensitive and CCCTC‐binding factor (CTCF)/cohesin‐binding sites with preferential DNA breakage in fusion‐driven patients. Importantly, measuring DSBs at these sites, in addition to the KMT2A gene region, provided greater predictive power when assessing individual break susceptibility. We also demonstrated that low‐dose etoposide exposure further elevated DNA breakage at these regions in fusion‐driven AML patients, but not in nonfusion patients, indicating that these sites are preferentially sensitive to TOP2 activity in fusion‐driven AML patients. These results support that mapping of DSBs in patients enables discovery of novel break‐prone regions and monitoring of individuals susceptible to chromosomal abnormalities, and thus cancer. This will build the foundation for early detection of cancer‐susceptible individuals, as well as those preferentially susceptible to therapy‐related malignancies caused by treatment with TOP2 poisons.
Experimental study on soda granites of the Singhbhum Craton, eastern India, and its petrogenetic significance
Authors: Ray Jyotisankar , Paul Madhuparna , Kar Rajib , Sheikh Janisar M. , Patel Suresh C. , Sinha Deepak Kumar , Sadasivan Rakesh , Alam Parvej , Chatterjee Sanchari , Sarma Samhati , Saha Ayendrila
Published: August 2021

The soda granite (~Paleoproterozoic) of the Singhbhum Craton (SC) of eastern India occurs along the entire stretch of the Singhbhum Shear Zone (SSZ; or Copper Belt Thrust Zone). The SSZ (marking a thrust contact between the adjacent North Singhbhum mobile belt and SC) serves as the important locale to host apatite‐magnetite, copper sulphide, and uraniferous mineralization. Typical field occurrence of soda granite is either as tongues (or patches) within a shear zone or as lit‐per‐lit style injections into surrounding country rocks which are generally highly sheared and mylonitized. Experimental studies on granite bodies can potentially throw light on their mineralogical and petrogenetic aspects; however, these studies are hitherto unreported in case of soda granites for almost the last 60 years. In this view, during the present research, experimental studies on soda granites have been carried out and these decipher the nature of the stability relationship of K‐feldspar (and transgression to more disordered anorthoclase), amphibole (both Ca‐amphibole and Fe–Mg–Mn amphibole and breaking down of Ca‐amphibole to Fe–Mg–Mn amphibole + non‐quad pyroxene + quartz at an appropriate temperature), biotite, muscovite, and albite (high albite‐ low albite displacive transformation). Whole‐rock chemistry (deduced from homogenized glass compositions) indicates its peraluminous, S‐type nature with an affinity towards Caledonian post‐collisional plutons. Characteristic geochemical plots suggest a pelitic source material for melting (and subsequent internal differentiation of the melt) and this has given rise to both migmatite as well as patchy soda granite exposures in the field. It is suggested that partial melting of mainly metapelitic (and minor mafic magmatic rocks) source (belonging to Singhbhum Series) gave rise to soda granites in this region.
Evidence for magma mixing during Triassic magmatism in West Qinling, China: Constraints from petrology, geochemistry, U–Pb zircon geochronology, and Sr–Nd–Hf isotopic of the Baguashan pluton
Authors: Li Xuefeng , Dong Guochen , Yu Xiaofei , Li Yongsheng , Santosh M. , Lv Xin , Xia Qing
Published: August 2021

The West Qinling Orogen, which forms the western part of the Qinling Orogenic Belt, is characterized by the voluminous distribution of Triassic granitoids. Here, we investigate the Baguashan monzogranite which hosts numerous mafic microgranular enclaves (MMEs). We present zircon U–Pb–Hf and whole‐rock geochemical as well as Sr–Nd isotopic data of the monzogranites and MMEs with a view to gain insights on the petrogenesis and geodynamic setting. Zircon LA‐ICP‐MS U–Pb dating yields ages of 219.0 ± 1.7 Ma and 219.5 ± 1.6 Ma for the MMEs, and 214.2 ± 1.3 Ma for the host monzogranite, suggesting formation from coeval magmas. The host monzogranites show high SiO2, Rb, Ba, and Th contents, but low TiO2, MgO, P2O5 values, with A/CNK of <1.1. Zircon grains from monzogranites show εHf(t) values in the range of −6.3 to +3.2 with corresponding two‐stage Hf model ages (TDM2) of 1.39–2.25 Ga. The MMEs are mostly elliptical or spherical in shape and have lower SiO2 and Th contents, but higher MgO, TiO2, and CaO, and εHf(t) values ranging from −6.1 to +5.7 with TDM2 of 1.17–2.23 Ga. The Sr–Nd isotopic data for MMEs and monzogranites show (87Sr/86Sr)i ratios ranging from 0.7059 to 0.7069 and low εNd(t) values ranging from −6.07 to −4.18, suggesting a crustal origin. Based on the relatively homogeneous Sr–Nd–Hf isotopic compositions, we suggest that the MMEs represent magma mixing, and the mafic magma injected into the felsic magma chamber was probably derived by the reworking of mafic lower crust with a contribution of juvenile materials. We propose a model involving delamination of thickened lower crust below the West Qinling Orogen after the collision between the North China Block and the South China Block in the Late Triassic. Subsequently, the lower crust was partially melted by the heat input from the upwelling asthenosphere and produced the mafic magma. Partial melting of the ancient metamorphic rocks generated the granitic magma. The interaction of mafic and felsic magmas occurred within a post‐collisional tectonic setting in the Late Triassic.
Preoperative prognostic factors for functional and clinical outcomes after open partial horizontal laryngectomies
Authors: Fantini Marco , Crosetti Erika , Affaniti Riccardo , Sprio Andrea Elio , Bertotto Ilaria , Succo Giovanni
Published: August 2021

Background

In minority of cases, the clinical recovery of the neolarynx after open partial horizontal laryngectomies (OPHLs) can be challenging, possibly affecting the final functional outcome.

Methods

One hundred and twenty‐three patients who underwent OPHLs were selected. A series of clinical preoperative independent variables were considered. All patients were monitored for the following dependent outcome variables: sequelae; need for percutaneous endoscopic gastrostomy positioning; days before tracheal cannula removal and nasogastric tube removal; and length of hospital stay. Univariate and multivariate logistic regression analyses were performed to identify significant associations between preoperative clinical variables and outcomes variables.

Results

Multivariate analysis confirmed age, cT classification, body mass index, and smoking habits as significant prognostic factors for worse functional and clinical recovery outcomes.

Conclusions

Knowing what variables are significantly associated with worse clinical and functional outcomes can guide clinicians in defining the best surgical choice not only from an oncological perspective, but also for a better postoperative recovery.
The Wasatch Environmental Observatory: A mountain to urban research network in the semi‐arid westernUS
Authors: Follstad Shah Jennifer J. , Bares Ryan , Bowen Brenda B. , Bowen Gabriel J. , Bowling David R. , Eiriksson David P. , Fasoli Benjamin , Fiorella Richard P. , Hallar Anna Gannet , Hinners Sarah J. , Horel John D. , Jacques Alexander A. , Jamison Logan R. , Lin John C. , Mendoza Daniel L. , Mitchell Logan E. , Pataki Diane E. , Skiles Sarah McKenzie , Smith Rose M. , Wolf Margaret A. , Brooks Paul D.
Published: August 2021

The 2085 km2Jordan River Basin, and its seven sub‐catchments draining the Central Wasatch Range immediately east of Salt Lake City, UT, are home to an array of hydrologic, atmospheric, climatic and chemical research infrastructure that collectively forms the Wasatch Environmental Observatory (WEO). WEO is geographically nested within a wildland to urban land‐use gradient and built upon a strong foundation of over a century of discharge and climate records. A 2200 m gradient in elevation results in variable precipitation, temperature and vegetation patterns. Soil and subsurface structure reflect systematic variation in geology from granitic, intrusive to mixed sedimentary clastic across headwater catchments, all draining to the alluvial or colluvial sediments of the former Lake Bonneville. Winter snowfall and spring snowmelt control annual hydroclimate, rapid population growth dominates geographic change in lower elevations and urban gas and particle emissions contribute to episodes of severe air pollution in this closed‐basin. Long‐term hydroclimate observations across this diverse landscape provide the foundation for an expanding network of infrastructure in both montane and urban landscapes. Current infrastructure supports both basic and applied research in atmospheric chemistry, biogeochemistry, climate, ecology, hydrology, meteorology, resource management and urban redesign that is augmented through strong partnerships with cooperating agencies. These features allow WEO to serve as a unique natural laboratory for addressing research questions facing seasonally snow‐covered, semi‐arid regions in a rapidly changing world and an excellent facility for providing student education and research training.
Impact of low‐level pretransplant donor‐specific antibodies on outcomes after kidney transplantation
Authors: Parajuli Sandesh , Bath Natalie M. , Hidalgo Luis , Leverson Glen , Garg Neetika , R. Redfield Robert , Mandelbrot Didier A.
Published: August 2021

Background

The effect of low‐level pretransplant donor‐specific antibody (DSA) on kidney transplant outcomes is not well described. The goal of this study was to compare outcomes among patients of varying immunologic risk, based on the level of pretransplant DSA.

Methods

We retrospectively reviewed all adult kidney transplant recipients who had undergone a transplant at our center between January 2013 and May 2017. Patients were grouped as negative DSA (mean fluorescence intensity, [MFISUM < 100]), low‐level DSA (MFISUM 100–1000), and positive DSA (MFISUM > 1000). Rejection, infection, graft, and patient survival were outcomes measured.

Results

Of 952 patients, 82.1% had negative DSA, 10.7% had low‐level DSA, and 7.1% had positive DSA. The positive DSA group had the highest rate of antibody‐mediated rejection (10.3%), followed by low‐level DSA (7.8%) and the negative DSA group (4.5%) (p = .034). The rate of BK viremia was highest in the positive DSA group (39.7%), followed by the low‐level group (30.4%) and the negative DSA group (25.6%), (p = .025). None of the other outcomes, including graft or patient survival, were different between the groups.

Conclusion

While low‐level DSA should not prevent proceeding with kidney transplantation, it should not be ignored. Future studies are needed to investigate the long‐term effects of varying levels of pre‐transplant DSA on outcomes.
The study on the function and cell source of interleukin‐6 in interstitial cystitis/bladder painful syndrome rat model
Authors: Zheng Zhenming , Zhang Jiapeng , Zhang Caixia , Li Wenshuang , Ma Kaiqun , Huang Hao , Li Kuiqing , Yao Yousheng
Published: August 2021

Objective

The elevated expression of interleukin‐6 (IL‐6) in patients with interstitial cystitis/bladder painful syndrome (IC/BPS) has been demonstrated, but the role of IL‐6 in IC/BPS and its source remain to be explored.

Methods

IC/BPS rat model was created in female rats by using long‐term intermittent intravesical hyaluronidase (0.5 ml, 4 mg/ml). After modeling, IL‐6 stimulation group, and anti‐IL‐6R group were treated with recombinant rat IL‐6 and tocilizumab, respectively. Symptomatic changes were detected by Vonfrey pain score and urodynamics, and hematoxylin‐eosin (HE) staining, mast cell staining and Masson staining were used to evaluate the changes of inflammation in the bladder tissue of rats. Cell sources of IL‐6 was explored through enzyme linked immunosorbent assay (ELISA) test, reverse transcription polymerase chain reaction (RT‐PCR), and western‐blot test on the supernatant of coculturing rat bladder epithelial cells and rat macrophages.

Results

The Vonfrey pain scores of the model group and IL‐6 stimulation group were significantly higher than those of the control group, while the anti‐IL‐6R group were significantly lower (p < .05). Compared with the blank control group, urodynamic results showed that the urination interval of the model group and IL‐6 stimulation group was significantly shortened, and the maximum bladder capacity was significantly reduced (p < .05), and anti‐IL‐6R treatment significantly alleviated the inflammatory response of bladder tissue. The results of HE, Mast cell staining, and Masson staining showed that the inflammatory response of bladder tissue after anti‐IL‐6R treatment was significantly reduced. Through cells coculture, the relative expression of IL‐6 from model group was found significantly higher than blank control group by RT‐PCR, ELISA, and western blot test (p < .05).

Conclusions

IL‐6 played an essential role in the development of IC/BPS rat model as a proinflammation cytokine. Further evidence from coculture proved that macrophages are the cell resource of IL‐6 in IC/BPS.
Design optimization of perforation on deflector for improved performance of vortex settling basin*
Authors: Mu Zhuoyun , Ma Yiyi , Li Lin
Published: August 2021

For vortex settling basins (VSBs) installed with a deflector, perforation is an effective retrofit to reduce the self‐weight of the deflector and sediment deposition on it. The current study investigated experimentally the performance of VSBs the deflector of which was perforated at different locations with various opening ratios. The results showed that perforating the outside overflow area of the deflector was the optimum for reducing sediment deposition. With an opening ratio of 8.67–13% in the outside overflow area of the deflector, the VSB exhibited similar sediment removal efficiency to the original design without any openings on the deflector. The current study provided the design optimization for deflector perforation in VSBs.
On the implementation of Cognitive Autonomous Networks
Authors: Banerjee Anubhab , Mwanje Stephen S. , Carle Georg
Published: August 2021

Cognitive Autonomous Networks (CAN) is a promising approach for advancing network management automation using machine learning based functions called Cognitive Functions (CFs). Thereby, the CFs interact with the environment to learn and decide suitable network configurations to optimize their objectives. To minimize conflicts among the actions of multiple CFs, the CFs send their proposed configurations to a Controller, which in turn computes the final value that optimizes the combined interest of all the CFs. However, simulating real‐life CAN deployments is challenging since: (a) the CFs have to reactively and interactively learn on the underlying system, and (b) the Controller must compute the optimal configurations in a dynamic environment with interdependent functions. In this letter, we present a scheme for implementing CAN in a simulation environment highlighting the critical design aspects for generating expected outcomes. Our results validate the proposed implementation design as the desired realistic behavior is obtained from CAN.
Ada, as seen from Simula
Authors: Krogdahl S. , Olsen K. A.
Published: August 2021

The programming language Ada* is discussed from a Simula point of view. Such a comparison is of special interest, as the two languages are based on different philosophies. Where Ada offers several constructs (record, package, task …), Simula has only one—the general class construct. The advantages and disadvantages of using such a high degree of categorization in Ada will be apparent from this comparison.
Using High Level Languages for Local Computer Network Communication: A Case Study in Ada*
Authors: Fantechi A. , Inverardi P. , Lijtmaer N.
Published: August 2021

This paper is focused on the design and implementation of an inter‐node communication mechanism for distributed programming on local computer network architectures using a high level language. Ada has been chosen and its suitability to cope with inter‐node communication will be discussed. A new communication mechanism has been developed using Ada abstraction mechanisms.
3D‐PulCNN: Pulmonary cancer classification from hyperspectral images using convolution combination unit based CNN
Authors: Zhang Qing , Wang Yan , Qiu Song , Chen Jiangang , Sun Li , Li Qingli
Published: August 2021

Pulmonary cancer is one of the most common malignancies worldwide. Accurate classification of its subtypes is required in differential diagnosis. However, existing algorithms are mostly based on color images, and the improvement of accuracy is quite challenging. In this study, we propose a convolution combination unit (CCU)‐based three‐dimensional convolutional neural network (3D‐PulCNN) for classifying pulmonary cancer presented in microscopic hyperspectral image with both spatial and spectral information. CCU is designed to fuse the features acquired by different convolution scales. Compared with VGGNet, only two fully connected layers are used in this model, reducing the network parameters and model complexity. Experimental results show that 3D‐PulCNN achieves overall average (OA) of 0.962 and Precision, Recall, and Kappa of more than 0.920, superior to 2D‐VGGNet. Then, 3D‐UNet is leveraged to segment cancer cells, and their morphological characteristics are calculated to supply quantitative virtual analysis data for classification results explanation and prognosis assessment.
Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model
Authors: Hixon Katherine R. , McKenzie Jennifer A. , Sykes David A.W. , Yoneda Susumu , Hensley Austin , Buettmann Evan G. , Zheng Hongjun , Skouteris Dimitrios , McAlinden Audrey , Miller Anna N. , Silva Matthew J.
Published: August 2021

Nonunion is defined as the permanent failure of a fractured bone to heal, often necessitating surgical intervention. Atrophic nonunions are a subtype that are particularly difficult to treat. Animal models of atrophic nonunion are available; however, these require surgical or radiation-induced trauma to disrupt periosteal healing. These methods are invasive and not representative of many clinical nonunions where osseous regeneration has been arrested by a “failure of biology”. We hypothesized that arresting osteoblast cell proliferation after fracture would lead to atrophic nonunion in mice. Using mice that express a thymidine kinase (tk) “suicide gene” driven by the 3.6Col1a1 promoter (Col1-tk), proliferating osteoblast lineage cells can be ablated upon exposure to the nucleoside analog ganciclovir (GCV). Wild-type (WT; control) and Col1-tk littermates were subjected to a full femur fracture and intramedullary fixation at 12 weeks age. We confirmed abundant tk+ cells in fracture callus of Col-tk mice dosed with water or GCV, specifically many osteoblasts, osteocytes, and chondrocytes at the cartilage-bone interface. Histologically, we observed altered callus composition in Col1-tk mice at 2 and 3 weeks postfracture, with significantly less bone and more fibrous tissue. Col1-tk mice, monitored for 12 weeks with in vivo radiographs and micro–computed tomography (μCT) scans, had delayed bone bridging and reduced callus size. After euthanasia, ex vivo μCT and histology showed failed union with residual bone fragments and fibrous tissue in Col1-tk mice. Biomechanical testing showed a failure to recover torsional strength in Col1-tk mice, in contrast to WT. Our data indicates that suppression of proliferating osteoblast-lineage cells for at least 2 weeks after fracture blunts the formation and remodeling of a mineralized callus leading to a functional nonunion. We propose this as a new murine model of atrophic nonunion. © 2021 American Society for Bone and Mineral Research (ASBMR).
PKD1 alleviates oxidative stress‐inhibited osteogenesis of rat bone marrow‐derived mesenchymal stem cells through TAZ activation
Authors: Chen Tongtong , Wang Hanqi , Jiang Chaoyin , Lu Yong
Published: August 2021

Oxidative stress is known to inhibit osteogenesis and PKD1 is implicated in bone remodeling and skeletogenesis. In the present study, we explored the role of PKD1 in osteogenesis under oxidative stress. H2O2 was used to induce oxidative stress in rat bone marrow (BM)‐mesenchymal stem cells (MSCs) during osteoblast differentiation. Alkaline phosphatase (ALP) activity, calcium deposits, and the RUNX2 marker were assayed to determine osteogenic differentiation. The correlation of PKD1, Sirt1, c‐MYC, and TAZ was further confirmed by chromatin immunoprecipitation (ChIP) and dual‐luciferase reporter assay. We found that H2O2 induced the downregulation of PKD1 expression and the upregulation of c‐MYC, and Sirt1 was accompanied by decreasing cell viability in BM‐MSCs. During osteogenic differentiation, the expression of PKD1 was upregulated significantly whereas Sirt1 tended to be upregulated mildly under normal conditions. Both PKD1 and Sirt1 were upregulated upon oxidative stress. The positive correlation of PKD1 expression with osteogenic differentiation under normal conditions might be hindered by oxidative stress and PKD1 could interact with TAZ under oxidative stress to regulate osteogenic differentiation. Our results suggest that PKD1 may alleviate oxidative stress‐inhibited osteogenesis of rat BM‐MSCs through TAZ activation.
The diagnostic value of the combination of hemoglobin, CA199, CA125, and HE4 in endometriosis
Authors: Chen Ting , Wei Jia‐Ling , Leng Ting , Gao Fei , Hou Shun‐yu
Published: August 2021

Background

We aimed to analyze the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people, and establish a more efficient combined diagnostic model.

Methods

We retrospectively analyzed the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people. Binary logistic regression analysis was used to establish a combined diagnostic model. We plotted the receiver operator characteristic (ROC) curve to analyze the diagnostic efficiency of different diagnostic indexes.

Results

Compared with patients in the control group, patients in the endometriosis group had significantly lower eosinophil% (p = 0.045), neutrophil (p = 0.001), lymphocyte (p < 0.001), red blood cells (RBCs) (p < 0.001), and hemoglobin (HGB) (p < 0.001), and had significantly higher monocyte% (p = 0.008), monocyte‐to‐lymphocyte ratio (MLR) (p = 0.001), platelet‐to‐lymphocyte ratio (PLR) (p < 0.001), carbohydrate antigen (CA)‐199 (p < 0.001), CA125 (p < 0.001), human epididymis protein (HE)‐4 (p < 0.001), and the risk of ovarian malignancy algorithm (ROMA) (p < 0.001). The combined diagnostic model of HGB, CA199, CA125, and HE4 was established by binary logistic regression analysis. The ROC curve showed that the combined diagnostic model reached a sensitivity of 85.4%, a specificity of 78.83%, and an area under the curve of 0.900, which was significantly higher than that of the individual index in endometriosis diagnosis.

Conclusion

The combined diagnostic model of HGB, CA199, CA125, and HE4 may provide a new approach for the early non‐invasive diagnosis of endometriosis.
The “Dark Side” of autophagy on the maintenance of genome stability: Does it really exist during excessive activation?
Authors: Cheng Siao Muk , Shieh Min‐Chieh , Lin Tzu‐Yu , Cheung Chun Hei Antonio
Published: August 2021

Dysregulation of DNA damage response/repair and genomic instability promote tumorigenesis and the development of various neurological diseases. Autophagy is a dynamic catabolic process used for removing unnecessary or dysfunctional proteins and organelles in cells. Despite the consensus in the field that upregulation of autophagy promotes the initiation of the DNA damage response and assists the process of homologous recombination upon genotoxic stress, a few studies showed that upregulation of autophagy (or excessive autophagy), under certain circumstances, triggers caspase/apoptosis‐independent DNA damage and promotes genomic instability in cells. As the cytoprotective and the DNA repairing roles of autophagy have been discussed extensively in different reviews, here, we mainly focus on describing the latest studies which reported the “opposite” roles of autophagy (or excessive autophagy). We will discuss whether the “dark side” (i.e., the opposite/unconventional effect) of autophagy on the maintenance of DNA integrity and genomic stability really does exist in cells and if it does, will it be one of the yet‐to‐be‐identified causes of cancer, in this review.
Chromatic number is Ramsey distinguishing
Authors: Savery Michael
Published: August 2021

A graph is Ramsey for a graph if every colouring of the edges of in two colours contains a monochromatic copy of . Two graphs and are Ramsey equivalent if any graph is Ramsey for if and only if it is Ramsey for . A graph parameter is Ramsey distinguishing if implies that and are not Ramsey equivalent. In this paper we show that the chromatic number is a Ramsey distinguishing parameter. We also extend this to the multicolour case and use a similar idea to find another graph parameter which is Ramsey distinguishing.
Role of IL-6 in dendritic cell functions
Authors: Xu Yu-Dong , Cheng Mi , Shang Pan-Pan , Yang Yong-Qing
Published: August 2021

Dendritic cells (DCs) are efficient antigen-presenting cells that serve as a link between the innate and adaptive immune systems. These cells are broadly involved in cellular and humoral immune responses by presenting antigens to initiate T cell reactions, cytokine and chemokine secretion, T cell differentiation and expansion, B cell activation and regulation, and the mediation of immune tolerance. The functions of DCs depend on their activation status, which is defined by the stages of maturation, phenotype differentiation, and migration ability, among other factors. IL-6 is a soluble mediator mainly produced by a variety of immune cells, including DCs, that exerts pleiotropic effects on immune and inflammatory responses through interaction with specific receptors expressed on the surface of target cells. Here, we review the role of IL-6, when generated in an inflammatory context or as derived from DCs, in modulating the biologic function and activation status of DCs and emphasize the importance of searching for novel strategies to target the IL-6/IL-6 signaling pathway as a means to diminish the inflammatory activity of DCs in immune response or to prime the immunogenic activity of DCs in immunosuppressive conditions.
Multiple epitopes of hepatitis B virus surface antigen targeted by human plasma‐derived immunoglobulins coincide with clinically observed escape mutations
Authors: Tarafdar Sreya , Virata Maria Luisa , Yan Hailing , Zhong Lilin , Deng Lu , Xu Yanqun , He Yong , Struble Evi , Zhang Pei
Published: August 2021

Hepatitis B immune globulin (HBIG) is a human plasma‐derived immunoglobulin G concentrate that contains a high titer of neutralizing antibodies (anti‐HBs) to the hepatitis B virus (HBV) surface antigen (HBsAg). HBIG is known to be highly effective in treating HBV infections, however, a more systematic characterization of the antibody binding sites on HBsAg and their correlation with emerging “escape” mutations in HBsAg was lacking. By using anti‐HBs antibodies from HBIG lots to screen random peptide phage display libraries, we identified five clusters of peptides that corresponded to five distinct anti‐HBs binding sites on the HBsAg. Three sites, Site II (C121‐C124), Site III (M133‐P135), and Site IV (T140‐G145), were mapped within the “a” determinant, while the two other sites, Site I (Q101‐M103) and Site V (I152‐S154), were outside the “a” determinant. We then tested in binding assays HBsAg peptides containing clinically relevant mutations previously reported within these sites, such as Y134S, P142S, and G145R, and observed a significant reduction in anti‐HBs binding activity to the mutated sites, suggesting a mechanism the virus may use to avoid HBIG‐mediated neutralization. The current HBIG treatment could be improved by supplementing it with site‐specific neutralizing monoclonal antibodies that target these mutations for control of HBV infections.
Impacts of cocoa pod maturity at harvest and bean fermentation period on the production of chocolate with potential health benefits
Authors: Tee Yei‐Kheng , Bariah Khairul , Hisyam Zainudin Badrul , Samuel Yap Kian‐Chee , Ong Ning‐Geng
Published: August 2021

BACKGROUND

Cacao beans are rich sources of polyphenols with an abundance of flavonoids and methylxanthines that have positive influences on human health. The main factors affecting the formation of flavor as well as the chemical and bioactive composition of cacao beans are cacao pod maturity and post‐harvest fermentation. The purpose of this research was to evaluate the effects of pod harvest maturity (mature and ripe) and post‐fermentation period (1, 3, and 5 days in a controlled temperature environment) measured by pre‐harvest maturity indices, post‐harvest quality tests, chemical measurements, and organoleptic evaluation.

RESULTS

As pods developed, flavonol accumulated while nitrogen content degraded. Mature pods produced beans with a higher flavonol, catechin, and total phenolic content (TPC). As fermentation progressed, the beans' fat, TPC, antioxidant activity, and catechin content increased, regardless of pod maturity at harvest. Free fatty acid (FFA) levels were highest in 5 day fermented beans. The 3 day fermented beans contained significantly higher epicatechin, with lower FFA content. Chocolate made from mature beans with 3 day fermentation was more pleasant as it scored the highest in flavor intensity and complexity and the lowest in acidity and astringency.

CONCLUSION

This study suggests that cacao pods harvested at the mature stage with further fermentation for 3 days under controlled temperatures produce specialty beans with potential health benefits. © 2021 Society of Chemical Industry.
Surgical resection of high‐grade nonfunctional pancreatic neuroendocrine carcinoma is associated with improved survival
Authors: Jiang Jerry , Park Joon , Kim Stephanie , Daan Amanda , Donahue Timothy , Girgis Mark D.
Published: August 2021

Background and objectives

The role of surgery in the treatment of nonfunctional pancreatic neuroendocrine carcinomas (PNEC) is not well defined. This study investigated the effect of surgical resection on cause‐specific survival compared with nonoperative management.

Methods

The Surveillance, Epidemiology, and End Results Program (SEER) database was utilized to identify patients with nonfunctional pancreatic neuroendocrine carcinoma diagnosed between January 1, 2004 and December 31, 2015. Survival was modeled using Kaplan–Meier analysis and multivariable Cox proportional hazards models.

Results

Of the 488 patients identified, 137 (29%) underwent surgical resection of the primary site. Patients who underwent surgery had a median CSS of 31 months compared with 5 months in those who did not (p < 0.01). A survival benefit was observed when the cohort was stratified into local, nodal, and metastatic disease.

Conclusion

Resection of the primary site in the cohort of PNEC patients compiled by SEER is associated with improved survival. Further consideration be placed on primary surgical resection for PNEC while additional studies that can select specifically for high‐grade, poorly differentiated carcinomas need to be undertaken.
Evaluation of multiple hydrophilic interaction chromatography columns and surrogate matrix for arginine quantification in saliva by high‐resolution mass spectrometry
Authors: Wang Yu , Hao Zhigang , Pan Long
Published: August 2021

Arginine, a pivotal ingredient in many biochemical synthetic pathways, can be used as a biomarker for many oral care clinical applications. It is still a challenge to develop a sensitive and reliable chromatographic method to quantify arginine as a biomarker in saliva, with or without arginine product pretreatment. The current method solved two critical issues for arginine quantitation in human saliva. The first issue was how to optimize arginine peak shape. A hydrophilic interaction chromatography method based on the column selection, pH and pKa relationship, mobile phase ionic strength, organic solvent consideration, and temperature effects was developed. An optimized chromatographic condition for arginine quantitation in the saliva matrix was obtained. The second issue was how to build confidence in the use of a simple surrogate matrix methodology to replace the more complex traditional standard addition methodology. The surrogate matrix methodology we developed is applicable to the measurement of arginine as a potential non‐invasive biomarker in human saliva. The method detection and quantification limit reached 2 and 6 ng/mL. The tailing factor was within the 0.9–1.1 range even though arginine had three pKa values at 2.18, 9.09, and 13.2.
Graft Survival and Segment Discards Among Split‐Liver and Reduced‐Size Transplantations in the United States From 2008 to 2018
Authors: Montgomery John R. , Highet Alexandra , Brown Craig S. , Waits Seth A. , Englesbe Michael J. , Sonnenday Christopher J.
Published: August 2021

Split‐liver transplantation has allocation advantages over reduced‐size transplantation because of its ability to benefit 2 recipients. However, prioritization of split‐liver transplantation relies on the following 3 major assumptions that have never been tested in the United States: similar long‐term transplant recipient outcomes, lower incidence of segment discard among split‐liver procurements, and discard of segments among reduced‐size procurements that would be otherwise “transplantable.” We used United Network for Organ Sharing Standard Transplant Analysis and Research data to identify all split‐liver (n = 1831) and reduced‐size (n = 578) transplantation episodes in the United States between 2008 and 2018. Multivariable Cox proportional hazards modeling was used to compare 7‐year all‐cause graft loss between cohorts. Secondary analyses included etiology of 30‐day all‐cause graft loss events as well as the incidence and anatomy of discarded segments. We found no difference in 7‐year all‐cause graft loss (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 0.8‐1.5) or 30‐day all‐cause graft loss (aHR, 1.1; 95% CI, 0.7‐1.8) between split‐liver and reduced‐size cohorts. Vascular thrombosis was the most common etiology of 30‐day all‐cause graft loss for both cohorts (56.4% versus 61.8% of 30‐day graft losses; P = 0.85). Finally, reduced‐size transplantation was associated with a significantly higher incidence of segment discard (50.0% versus 8.7%) that were overwhelmingly right‐sided liver segments (93.6% versus 30.3%). Our results support the prioritization of split‐liver over reduced‐size transplantation whenever technically feasible.
A mediated–moderated model for social media adoption and small and medium‐sized enterprise performance in emerging countries
Authors: Qalati Sikandar Ali , Ostic Dragana , Shuibin Gu , Mingyue Fan
Published: August 2021

Social media adoption (SMA) can enable small and medium‐sized enterprises (SMEs) to build strong relationships with customers at low cost, addressing the global challenge of SME's growth and sustainability. In the under‐examined developing‐country context, this study aims to explore the mediating role of SMA and customer relationship management capabilities (CRMC) and the moderating role of innovation capabilities (IC) and SMA. Grounded on the resource‐based view, 431 randomly selected closed‐ended‐questionnaire responses were analyzed. Findings reveal the positive and significant effect of entrepreneurial orientation (EO), SMA, CRMC, and IC on SME performance (SMEP), as well as the partially mediating role of SMA and CRMC and the moderating role of IC on the SMA–SMEP relationship.
Multitarget Transcranial Electrical Stimulation for Freezing of Gait: A Randomized Controlled Trial
Authors: Manor Brad , Dagan Moria , Herman Talia , Gouskova Natalia A. , Vanderhorst Veronique G. , Giladi Nir , Travison Thomas G. , Pascual‐Leone Alvaro , Lipsitz Lewis A. , Hausdorff Jeffrey M.
Published: August 2021

Background

Treatments of freezing of gait (FOG) in Parkinson's disease are suboptimal.

Objective

The aim of this study was to evaluate the effects of multiple sessions of transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex and primary motor cortex (M1) on FOG.

Methods

Seventy‐seven individuals with Parkinson's disease and FOG were enrolled in a double‐blinded randomized trial. tDCS and sham interventions comprised 10 sessions over 2 weeks followed by five once‐weekly sessions. FOG‐provoking test performance (primary outcome), functional outcomes, and self‐reported FOG severity were assessed.

Results

Primary analyses demonstrated no advantage for tDCS in the FOG‐provoking test. In secondary analyses, tDCS, compared with sham, decreased self‐reported FOG severity and increased daily living step counts. Among individuals with mild‐to‐moderate FOG severity, tDCS improved FOG‐provoking test time and self‐report of FOG.

Conclusions

Multisession tDCS targeting the left dorsolateral prefrontal cortex and M1 did not improve laboratory‐based FOG‐provoking test performance. Improvements observed in participants with mild‐to‐moderate FOG severity warrant further investigation. © 2021 International Parkinson and Movement Disorder Society