bluuebunny/crossref_metadata_2025 huggingface dataset:
Leading With Values
Authors: Malhotra Neil , Shotts Ken
Published: January 2022

As societies become more polarized, there is increasing pressure for business leaders to have a sense of purpose and to make moral decisions. Being a good leader requires both a keen understanding of the realities of human decision making as well as an analysis of what is right and wrong. This book integrates lessons from three intellectual traditions – psychology, philosophy, and political economy – to guide readers on a journey to rigorously explore their values and decision making. The authors begin by examining people's intuitions about right and wrong. They then clarify principles that embody these intuitions and help readers engage with others whose intuitions or principles differ from their own. Ultimately, this book teaches readers how to be strategic as they lead with their values: as individuals, as designers of organizations, and as businesspeople interacting with societal institutions.
Regulating Public Services
Authors: Auriol Emmanuelle , Crampes Claude , Estache Antonio
Published: January 2022

Regulation is one of the tools used by governments to control monopolistic behaviour in the provision of public services such as electricity, transport or water. Technological and financial innovations have changed these public services markets since the 1990s, bringing new regulatory challenges, including technological and financial ones. This book demonstrates that basic regulatory theory and tools can address these new challenges, in addition to more traditional regulatory issues, both in developed and developing economies. The theory covered in the book is robust enough to guide regulators in multiple contexts, including those resulting from the effects of financial or political constraints, evolving market structures or the need to adapt to institutional weaknesses, climate change and poverty concerns that demand regulatory intervention. A bridge between theory and an evolving global practice, this book mobilizes the lessons of the past to analyse the future of economic regulation.
The Rise and Fall of Anti-Corruption in North Korea
Authors: Carothers Christopher
Published: January 2022

North Korea is widely seen as having among the most corrupt governments in the world. However, the Kim family regime has not always been so accepting of government wrongdoing. Drawing on archival evidence, this study shows that Kim Il-sung saw corruption as a threat to economic development and launched campaigns to curb it throughout the 1950s. I find that these campaigns were at least somewhat successful, and they contributed to post-Korean War reconstruction and rapid development afterwards. So when and why did the regime shift from combating corruption to embracing it? I argue that changes in the country's economic system following the crisis of the 1990s, especially de facto marketization, made corruption more beneficial to the regime both as a source of revenue and as an escape valve for public discontent. This study's findings contribute to our understanding of the politics of corruption control in authoritarian regimes.
Between Wisdom and Apocalypse: Reading Tosefta Soṭah Chapters 10–15
Authors: Rosen-Zvi Ishay
Published: January 2022

Chapters 10–15 in Tosefta Soṭah contain the longest, most elaborated aggadic unit in the Tosefta. It comprises various units that seem to be connected only loosely: the biblical righteous figures who brought abundance to the world (chs. 10–12); various revelations and appearances of the holy spirit and divine echo (ch. 13); and the effects of the destruction and the calamities of the present (chs. 14–15). In this article I argue that it forms in fact a coherent unit. It combines apocalyptic, priestly, and wisdom themes in a manner that is unprecedented in rabbinic literature, but is similar to several Second Temple texts. It tells a tale of perpetual decline from the biblical golden age to the rabbis’ own age of destruction, together with its eschatological remedy. It combines priestly and apocalyptic themes to form an alternative to the standard rabbinic meta-narrative of the transfer from prophecy to Torah. The first section of the article discusses chapters 10–13 and reconstructs their meticulous similarity with, and influence by, Ben Sira; the second section compares the complete composite unit (chs. 10–15) to the parallel Mishnah; and the third section examines the apocalyptic themes found in our text. I end with the need to reevaluate the relationship between rabbinic literature and apocalypticism.
Determinants influencing cholesteatoma recurrence in daily practice: a retrospective analysis
Authors: Adriaansens C , Bekkers S , Aarts M C J
Published: January 2022

Background

Cholesteatoma is a benign but destructive epithelial lesion in the middle ear and/or mastoid. It is hard to translate data from previous research to daily clinical practice. In this study, factors influencing recurrence rates in daily clinical practice were identified.

Method

The study included 67 patients who were treated for a cholesteatoma with combined approach tympanoplasty. The average follow-up time was 35 months.

Results

The recurrence rate was 23.3 per cent in adults and 45.5 per cent in children. Predictors of recurrence were younger age and a low tegmen. A cholesteatoma in a child and the simultaneous presence of a low tegmen led to recurrence in 82.8 per cent of the patients.

Conclusion

Patients – especially children – with a low tegmen have an increased risk of recurrence. It is recommended that ENT surgeons be aware of recurrence in children, particularly in the case of a low tegmen.
Sensorineural hearing loss following lumbar puncture, spinal anaesthesia or epidural anaesthesia: a case series and literature review
Authors: Alwan M , Hurtado G
Published: January 2022

Background

Sensorineural hearing loss following spinal anaesthesia, epidural anaesthesia or lumbar puncture is a rare phenomenon that is thought to occur when reduced cerebrospinal fluid pressure is transmitted to the inner ear through an enlarged cochlear aqueduct.

Method

This study presents two cases of sensorineural hearing loss following spinal anaesthesia for caesarean section as well as presenting results of a systemic review of the available literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text articles from Medline, PubMed and Embase were used, as well as associated reference lists. Risk factors associated with poorer outcomes and an approach to management of this rare condition are also discussed.

Results

Twenty-one cases were identified. The literature was systematically reviewed showing presentations, investigations performed, treatments offered and outcomes.

Conclusion

Sensorineural hearing loss following spinal anaesthesia, epidural anaesthesia or lumbar puncture is a rare occurrence that requires a high degree of clinical suspicion and prompt investigation and treatment.
Socio-economic and technological aspects of mental health of older persons: the role of strong and weak ties in Ghana
Authors: Amoah Padmore Adusei , Osei-Tutu Annabella , Adjei Stephen Baffour
Published: January 2022

Research indicates that social capital can influence the extent to which socio-economic status (SES) and information and communications technology (ICT) affect mental health. This study uses empirical data to examine the veracity of this claim by examining the effect of SES and ICT use on the mental health of older persons in Ghana, as well as the moderating role of bonding (i.e. strong ties) and bridging (i.e. weak ties) social capital in these associations. Data were drawn from 409 older persons from four regions in Ghana as part of a broader cross-sectional survey. Ordinal logistic regression analyses showed that SES and ICT use had positive associations with mental health after adjusting for other socio-demographic factors. Bridging social capital modified the association between SES and mental health positively. Bonding social capital also moderated the relations between ICT use on mental health positively. We argue that the prevalent nature of resources embedded in strong ties and the diversity of support that emerge from weak ties account for the difference in their influence observed in this study. Thus, while advances in socio-economic and technological conditions can enhance older persons’ mental health, equal attention must be paid to the characteristics of their strong and weak ties as they possess the resources to make socio-technological policies even more meaningful.
Strong Warming Rates in the Surface and Bottom Layers of a Boreal Lake: Results From Approximately Six Decades of Measurements (1964–2020)
Authors: Noori Roohollah , Bateni Sayed M. , Saari Markus , Almazroui Mansour , Torabi Haghighi Ali
Published: January 2022

High‐latitude lakes are warming faster than the global average with deep implications for life on Earth. Using an approximately six‐decade long in situ data set, we explored the changes in lake surface‐water temperature (LST), lake deep‐water temperature (LDT), lake depth‐weighted mean water temperature (LDMT), and ice‐free days in Lake Kallavesi, a boreal lake in central Finland, when the lake was stratified (June–August). Our results suggest that the LST is warming faster than the local air temperature (AT). As for the LST, fast warming was also observed in the LDT and LDMT, but at rates slower than those in the LST. The number of ice‐free days also shows an upward trend, with a rate of about 7 days per decade during the study period. The corresponding local AT is the main driver of the LST, followed by the ice‐free days and annual mean AT. Air temperature and ice‐free days also mainly contribute to the changes in the LDMT. The LDT is affected more by the North Atlantic Oscillation signals in this freshwater lake. The AT in the prior months does not affect the LDT in Lake Kallavesi although the AT during the prior season, that is, spring, is the main driver of summer LDT. This highlights the local AT impact on the LDT at time scales longer than a month. The warming rates in the lake water are at a minimum in June because the lake is not yet strongly stratified in this month when compared to July and August. These findings improve our knowledge of long‐term changes in the lake water temperature in a high‐latitude lake, a region with severe environmental consequences due to fast changes in the AT and lake ice phenology.
SORCE and TSIS‐1 SIM Comparison: Absolute Irradiance Scale Reconciliation
Authors: Harder Jerald , Béland Stéphane , Penton Steven V. , Richard Erik , Weatherhead Elizabeth , Araujo‐Pradere Eduardo
Published: January 2022

The Solar Radiation and Climate Experiment (SORCE) and Total and Spectral Irradiance Sensor (TSIS‐1) conducted an intercomparison for the two Spectral Irradiance Monitors (SIM) spanning 704 days from 23 March 2018 to 25 February 2020 and permitted 554 time‐matched pairs of observations. This comparison was conducted during the extremely quiescent Solar Cycle 24 minimum, so all observed differences and drifts between the two sensors are instrumental in nature. The TSIS‐1 SIM benefitted from advanced calibration capabilities based on SI standards that were not available during the preflight calibration time period of SORCE. For this reason, a revision of the SORCE SIM absolute scale is appropriate. As expected, wavelength dependent differences in absolute agreement are a function of detector sensitivity and local changes in spectral slope. At the time of the comparison SORCE SIM has been on‐orbit for 17 years while TSIS‐1 observations commenced immediately after a 100‐day outgassing and commissioning period. Peak‐to‐peak absolute scale differences are about 12% with a mean fractional difference of 0.7% ± 2.9%. The greatest scale differences occur at the change‐over between the UV and visible photodiodes in the 310 nm region, and a systematic disagreement is present in the 850–1,600 nm range. A multiplicative scale correction factor has been developed to reconcile the TSIS‐1 and SORCE difference with a wavelength dependent error on the mean typically less than 0.01% derived from every matched pair of observations.
Duvalo “Volcano” (North Macedonia): A Purely Tectonic‐Related CO2 Degassing System
Authors: Li Vigni L. , Cardellini C. , Temovski M. , Ionescu A. , Molnár K. , Palcsu L. , Gagliano A. L. , Cappuzzo S. , D’Alessandro W.
Published: January 2022

Duvalo “volcano” is a site of anomalous geogenic degassing close to Ohrid (North Macedonia) not related to volcanic activity, despite its name. CO2 flux measurements made with the accumulation chamber (321 sites over ∼50,000 m2) showed fluxes up to nearly 60,000 g m−2 d−1, sustaining a total output of ∼67 t d−1. Soil gas samples were taken at 50 cm depth from sites with high CO2 fluxes and analyzed for their chemical and isotope composition. The gas is mainly composed by CO2 (>90%) with significant concentrations of H2S (up to 0.55%) and CH4 (up to 0.32%). The isotope compositions of He (R/RA 0.10) and of CO2 (δ13C ∼ 0‰) exclude significant mantle contribution, while δ13C‐CH4 (∼−35‰) and δ2H‐CH4 (∼−170‰) suggest a thermogenic origin for CH4. The area is characterized by intense seismic activity and Duvalo corresponds to an active tectonic structure bordering the Ohrid graben. The production of H2S within the stratigraphic sequence may be explained by thermochemical reduction of sulfate. The uprising H2S is partially oxidized to sulfuric acid that, reacting with carbonate rocks, releases CO2. The tectonic structure of the area favors fluid circulation, sustaining H2S production and oxidation, CO2 production and allowing the escape of the gases to the atmosphere. In the end, Duvalo represents a tectonic‐related CO2 degassing area whose gases originate mostly, if not exclusively, in the shallowest part of the crust (<10 km). This finding highlights that even systems with trivial mantle contribution may sustain intense CO2 degassing (>1,000 t km−2 d−1).
Precipitation Dependence of Temperature Trends Across the Contiguous US
Authors: Abatzoglou John T. , Marshall Adrienne M. , Lute A. C. , Safeeq Mohammad
Published: January 2022

Temperature and precipitation covary across timescales due to thermodynamic and dynamic processes. We examine spatial patterns and trends of daily precipitation dependence of maximum and minimum temperature anomalies across the contiguous United States during 1950–2020. In the warm season, maximum temperatures are anomalously cool on wet days, while in the cool season, minimum temperatures are anomalously warm on wet days. During 1950–2020, warm‐season maximum temperatures increased 0.5°C more on wet days than on dry days, whereas minimum temperature on dry days warmed slightly more than on wet days in both the warm and cool season. By contrast, climate models show more subtle and consistent precipitation dependence of temperature trends with approximately 0.2°C more warming on dry days than on wet days. Improved understanding of precipitation‐dependent temperature trends is critical for understanding and modeling the impacts of changing climate on snowpack, drought, and heat stress.
Impact of Dust on Climate and AMOC During the Last Glacial Maximum Simulated by CESM1.2
Authors: Zhang Ming , Liu Yonggang , Zhu Jiang , Wang Zhuoqun , Liu Zhengyu
Published: January 2022

While the impact of dust on climate and Atlantic Meridional Overturning Circulation (AMOC) during the interglacial period such as the mid‐Holocene has been studied extensively, its impact during the glacial period is unclear. Here we investigate how the climate and AMOC would change if there had been no dust during the Last Glacial Maximum. Model simulations show that the dust removal leads to a global cooling of over 2.4°C and a weakening of AMOC by ∼30%. Such temperature change is opposite in sign to that for the MH. The cooling is attributed to the increase of snow and ice albedo and weakening of AMOC when dust is removed, and is amplified through a positive feedback between sea ice and AMOC. Our results indicate that the climate and AMOC are more sensitive to dust change during the glacial than the interglacial period.
Performance of Cloud 3D Solvers in Ice Cloud Shortwave Radiation Closure Over the Equatorial Western Pacific Ocean
Authors: Ren Tong , Yang Ping , Wei Jian , Huang Xianglei , Sang Huiyan
Published: January 2022

For retrieving cloud optical properties from satellite images or computing these properties from climate model output, computationally efficient treatments of cloud horizontal inhomogeneity include the Monte Carlo Independent Column Approximation (McICA) and the Tripleclouds method. Computationally efficient treatment of cloud horizontal radiation exchanges includes the SPeedy Algorithm for Radiative TrAnsfer through CloUd Sides (SPARTACUS). As a test to derive properties from satellite images, we collocate Moderate Resolution Imaging Spectroradiometer (MODIS) cloud retrievals with near‐nadir Cloud and the Earth's Radiant Energy System (CERES) footprints in July 2008 over an equatorial western Pacific Ocean region to compare the performance of the McICA, Tripleclouds, and SPARTACUS solvers to the conventional plane‐parallel homogeneous (PPH) treatment. PPH overestimates cloud albedo, and the three solvers effectively reduce overestimation with root mean square error of shortwave upwelling irradiance decreasing between 15.72 and 18.53 W m−2, or about 22%–25%. Although cloud top variability does not get fed into the simulations, all three solvers also reduce the effect of cloud top variability on cloud albedo. Entrapment (energy reflected downward from clouds) and horizontal radiation transfer have opposite effects on the SPARTACUS cloud albedo simulation. The net effect depends on the cloud vertical extent, the unawareness of which limits the performance of the SPARTACUS solver.
Magnetic Properties of the Ganzi Loess and Their Implications for Precipitation History in the Eastern Tibetan Plateau Since the Last Interglacial
Authors: Yang Shengli , Chen Zixuan , Chen Hui , Luo Yuanlong , Liu Li , Liu Xiaojing , Li Qiong , Zhou Jiantao , Li Pushuang
Published: January 2022

Loess sequences in the eastern Tibetan Plateau (TP) are valuable paleoenvironmental archives for reconstructing the environmental history related to the Indian summer monsoon (ISM). We conducted a detailed environmental magnetism analysis of the Ganzi loess sequence that developed since the Last Interglacial (LIG) and reconstructed the paleo‐precipitation history by analyzing multiple magnetic parameters. Our results are as follows: (a) Magnetic minerals of the Ganzi loess are mainly maghemite and magnetite, with high concentrations of magnetic minerals in the paleosol layer. The pedogenic ferrimagnetic particles dominated the magnetic enhancement, and magnetic parameters can be used to reconstruct precipitation history. (b) Precipitation reconstructed by using the multiple magnetic parameters of the Ganzi loess shows that rainfall in the eastern TP has varied dramatically, and the wettest periods over the last glacial cycle were the LIG and the Holocene. (c) The ISM has influenced precipitation changes since the LIG in the eastern TP. The ISM and precipitation in the eastern TP were mainly driven by the combined effect of orbital changes, global ice volume, atmospheric CO2 concentration, and internal climate forcing on the glacial‐interglacial timescale.
Human Intervention Will Stabilize Groundwater Storage Across the North China Plain
Authors: Yang Wenting , Long Di , Scanlon Bridget R. , Burek Peter , Zhang Caijin , Han Zhongying , Butler James J. , Pan Yun , Lei Xiaohui , Wada Yoshihide
Published: January 2022

The North China Plain (NCP) has been subjected to groundwater overexploitation over the past decades as a result of rapid socioeconomic development and irrigation water demand with relatively limited renewable water resources. Operation of the middle route of the South‐to‐North Water Diversion Project (SNWD‐M) since December 2014 has provided an opportunity for groundwater sustainability in the NCP by increasing water supply and reducing groundwater abstraction. Water use changes have largely been driven by socioeconomic changes. However, impacts of water diversion, water use change, as well as climate variability in the future on groundwater storage (GWS) in the NCP have not been investigated. This study aims to simulate and project GWS in the NCP during 2005–2050 by incorporating effects of water diversion, water use, and climate variability. The high‐resolution Community Water Model with 30 arcsec spatial resolution was set up to assess interactions between water demand and availability by simulating surface water and groundwater abstraction dynamically. Results show that water diversion and reductions in water use may increase GWS over the NCP in 2050 by 144 mm (19 km3) and 573 mm (75 km3), respectively. Evaluation of GWS among different scenarios shows that combinations of factors, including water use reductions, water diversion, and precipitation variability can contribute up to 73%, 37%, and 32% to GWS stability, respectively. This study highlights the contributions of different management strategies toward sustainable GWS and the importance of water conservation along with diversions.
An Objective Time‐Series‐Analysis Method for Rainfall‐Runoff Event Identification
Authors: Giani G. , Tarasova L. , Woods R. A. , Rico‐Ramirez M. A.
Published: January 2022

Methodologies for rainfall‐runoff event identification from continuous time series suffer from significant subjectivity. In particular, whether they initiate the identification from rainfall or from the streamflow timeseries, they usually require baseflow separation and they need substantial modifications and parameters’ recalibration when changing temporal resolution of the data. Therefore, here we propose a novel objective methodology for event identification that is easily transferable across sites and temporal resolutions, without having to make subjective choices and adjust multiple parameters. The proposed method to identify rainfall‐runoff events is based on a time series analysis technique that simultaneously considers rainfall and streamflow time series and does not make any a priori assumptions about baseflow separation. The novel method allows also to produce a baseflow separation a posteriori by connecting the delimiters of identified streamflow events. Moreover, the proposed method can be applied at any time resolution as long as the resolution is high enough to capture the time delay between precipitation and runoff response. When comparing the results between the proposed and the traditional baseflow‐based event identification approach, we observe a good agreement in terms of event properties both at hourly and daily scale (correlation of runoff ratios between the two methods equal to 0.78 [daily data] and 0.84 [hourly data]). The analysis comparing hourly and daily event identifications with the proposed method reveals also that the novel method produces coherent events across different temporal resolutions (correlation of runoff ratios between daily and hourly data equal to 0.71).
The role of complement C5a receptor in DPSC odontoblastic differentiation and in vivo reparative dentin formation
Authors: Irfan Muhammad , Kim Ji-Hyun , Marzban Hassan , Reed David A. , George Anne , Cooper Lyndon F. , Chung Seung
Published: January 2022

Therapeutic dentin regeneration remains difficult to achieve, and a majority of the attention has been given to anabolic strategies to promote dentinogenesis directly, whereas, the available literature is insufficient to understand the role of inflammation and inflammatory complement system on dentinogenesis. The aim of this study is to determine the role of complement C5a receptor (C5aR) in regulating dental pulp stem cells (DPSCs) differentiation and in vivo dentin regeneration. Human DPSCs were subjected to odontogenic differentiation in osteogenic media treated with the C5aR agonist and C5aR antagonist. In vivo dentin formation was evaluated using the dentin injury/pulp-capping model of the C5a-deficient and wild-type mice. In vitro results demonstrate that C5aR inhibition caused a substantial reduction in odontogenic DPSCs differentiation markers such as DMP-1 and DSPP, while the C5aR activation increased these key odontogenic genes compared to control. A reparative dentin formation using the C5a-deficient mice shows that dentin regeneration is significantly reduced in the C5a-deficient mice. These data suggest a positive role of C5aR in the odontogenic DPSCs differentiation and tertiary/reparative dentin formation. This study addresses a novel regulatory pathway and a therapeutic approach for improving the efficiency of dentin regeneration in affected teeth.
Structural biology of SARS-CoV-2: open the door for novel therapies
Authors: Yan Weizhu , Zheng Yanhui , Zeng Xiaotao , He Bin , Cheng Wei
Published: January 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of the pandemic disease COVID-19, which is so far without efficacious treatment. The discovery of therapy reagents for treating COVID-19 are urgently needed, and the structures of the potential drug-target proteins in the viral life cycle are particularly important. SARS-CoV-2, a member of the Orthocoronavirinae subfamily containing the largest RNA genome, encodes 29 proteins including nonstructural, structural and accessory proteins which are involved in viral adsorption, entry and uncoating, nucleic acid replication and transcription, assembly and release, etc. These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities. This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis, providing insights into the mechanisms underlying viral infection, prevention of infection, and treatment. Indeed, these studies open the door for COVID therapies, leading to ways to prevent and treat COVID-19, especially, treatment of the disease caused by the viral variants are imperative.
Patients in complete remission after R-CHOP(-like) therapy for diffuse large B-cell lymphoma have limited excess use of health care services in Denmark
Authors: Jakobsen Lasse Hjort , Øvlisen Andreas Kiesbye , Severinsen Marianne Tang , Bæch Joachim , Kragholm Kristian Hay , Glimelius Ingrid , Gang Anne Ortved , Jørgensen Judit Mészáros , Frederiksen Henrik , Poulsen Christian Bjørn , Clausen Michael Roost , Pedersen Per Trøllund , Pedersen Robert Schou , Torp-Pedersen Christian , Eloranta Sandra , El-Galaly Tarec Christoffer
Published: January 2022

For most patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), R-CHOP immunochemotherapy leads to complete remission and 60–70% of patients remain progression-free after 5 years. Given a median age of 65, it is relevant to disentangle how DLBCL and DLBCL therapy influence health care use among the survivors. In this nationwide study, the health care use among Danish DLBCL patients diagnosed in 2007–2015, who achieved complete remission after R-CHOP(-like) therapy, was explored and compared to matched comparators from the Danish general population. The post-remission 5-year risk of hospitalization was significantly higher among DLBCL survivors (55%) compared to matched comparators (49%, P < 0.001). DLBCL survivors had on average 10.3 (9.3–11.3) inpatient bed days within 5 years of response evaluation, whereas matched comparators had 8.4 (7.9–8.8). The rate of outpatient visits was also significantly higher(excluding routine follow-up visits, incidence rate ratio, 1.3, P < 0.001), but translated into only a very small absolute difference of <1 outpatient visits within 5 years between DLBCL survivors (4.2 visits, 95% CI, 4.0–4.4) and matched comparators (3.8 visits, 95% CI, 3.7–3.9). In conclusion, DLBCL survivors have an increased incidence of hospital visits due to a wide range of conditions, but in absolute terms the excess use of health care services in DLBCL survivors was small.
Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38+ macrophages and NAD+ decline
Authors: Ciaglia Elena , Lopardo Valentina , Montella Francesco , Carrizzo Albino , Di Pietro Paola , Malavolta Marco , Giacconi Robertina , Orlando Fiorenza , Cattaneo Monica , Madeddu Paolo , Vecchione Carmine , Puca Annibale Alessandro
Published: January 2022

As we age, our body experiences chronic, systemic inflammation contributing to the morbidity and mortality of the elderly. The senescent immune system has been described to have a causal role in driving systemic aging and therefore may represent a key therapeutic target to prevent pathological consequences associated with aging and extend a healthy lifespan. Previous studies from our group associated a polymorphic haplotype variant in the BPIFB4 gene (LAV-BPIFB4) with exceptional longevity. Transfer of the LAV-BPIFB4 in preclinical models halted the progression of cardiovascular diseases (CVDs) and frailty by counterbalancing chronic inflammation. In the present study, we aimed to delineate the action of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer (AAV-LAV-BPIFB4) on the deleterious age-related changes of the immune system and thereby the senescence-associated events occurring in C57BL/6J mice aged 26 months. Our in vivo data showed that 26-months-old mice had a higher frequency of CD45+SA-beta Gal+immune cells in peripheral blood than young (4-months-old) C57BL/6J mice. Notably, AAV-LAV-BPIFB4 gene transfer in aged mice reduced the pool of peripheral immunosenescent cells that were shown to be enriched in the spleen. In addition, the proper tuning of the immune secretory phenotype (IL1βlow, IL6low, IL10high) associated with a significant reduction in SA-beta Gal-positive area of aorta from AAV-LAV treated mice. At the functional level, the reduction of senescence-associated inflammation ensured sustained NAD+levels in the plasma of AAV-LAV-BPIFB4 old mice by preventing the NADase CD38 increase in F4/80+ tissue-resident macrophages and Ly6Chighpro-inflammatory monocytes of the spleen and bone marrow. Finally, to validate the clinical implication of our findings, we showed that Long-living-individuals (LLIs, >95 years), which delay CVDs onset, especially if LAV-carriers, were characterized by high NAD+levels. In conclusion, the new senotherapeutic action of LAV-BPIFB4 may offer a valuable therapeutic tool to control aging and reduce the burden of its pathophysiological disorders, such as CVDs.
A molecular atlas of innate immunity to adjuvanted and live attenuated vaccines, in mice
Authors: Lee Audrey , Scott Madeleine K. D. , Wimmers Florian , Arunachalam Prabhu S. , Luo Wei , Fox Christopher B. , Tomai Mark , Khatri Purvesh , Pulendran Bali
Published: January 2022

Adjuvants hold great potential in enhancing vaccine efficacy, making the understanding and improving of adjuvants critical goals in vaccinology. The TLR7/8 agonist, 3M-052, induces long-lived humoral immunity in non-human primates and is currently being evaluated in human clinical trials. However, the innate mechanisms of 3M-052 have not been fully characterized. Here, we perform flow cytometry, single cell RNA-seq and ATAC-seq to profile the kinetics, transcriptomics and epigenomics of innate immune cells in murine draining lymph nodes following 3M-052-Alum/Ovalbumin immunization. We find that 3M-052-Alum/OVA induces a robust antiviral and interferon gene program, similar to the yellow fever vaccine, which is known to confer long-lasting protection. Activation of myeloid cells in dLNs persists through day 28 and single cell analysis reveals putative TF-gene regulatory programs in distinct myeloid cells and heterogeneity of monocytes. This study provides a comprehensive characterization of the transcriptomics and epigenomics of innate populations in the dLNs after vaccination.
Polycrystalline morphology and mechanical strength of nanotube fibers
Authors: Gupta Nitant , Penev Evgeni S. , Yakobson Boris I.
Published: January 2022

Correlating mechanical performance with mesoscale structure is fundamental for the design and optimization of light and strong fibers (or any composites), most promising being those from carbon nanotubes. In all forms of nanotube fiber production strategies, due to tubes’ mutual affinity, some degree of bundling into liquid crystal-like domains can be expected, causing heterogeneous load transfer within and outside these domains, and having a direct impact on the fiber strength. By employing large-scale coarse-grained simulations, we demonstrate that the strengthsof nanotube fibers with characteristic domain sizeDscales ass ~ 1/D, while the degree of longitudinal/axial disorder within the domains (akin to a smectic ↔ nematic phase transition) can substantially mitigate this dependence.
The 1-minute sit-to-stand test to detect desaturation during 6-minute walk test in interstitial lung disease
Authors: Oishi Keiji , Matsunaga Kazuto , Asami-Noyama Maki , Yamamoto Tasuku , Hisamoto Yukari , Fujii Tetsuya , Harada Misa , Suizu Junki , Murakawa Keita , Chikumoto Ayumi , Matsuda Kazuki , Kanesada Haruka , Kikuchi Yujiro , Hamada Kazuki , Uehara Sho , Suetake Ryo , Ohata Syuichiro , Murata Yoriyuki , Yamaji Yoshikazu , Sakamoto Kenji , Ito Kosuke , Osoreda Hisayuki , Edakuni Nobutaka , Kakugawa Tomoyuki , Hirano Tsunahiko , Yano Masafumi
Published: January 2022

Although the 6 min walk test (6MWT) is well-established for assessing desaturation in patients with interstitial lung disease (ILD), it cannot be easily performed in primary healthcare settings. This retrospective observational study aimed to evaluate the usefulness of the 1 min sit-to-stand test (1STST) for assessing desaturation during 6MWT in ILD patients with normal resting blood oxygen levels. We included 116 patients, and the pulse oxygen saturation (SpO2) for both methods was analyzed. The SpO2 nadir during the 1STST and 6MWT correlated strongly (ρ = 0.82). The frequency of patients with nadir SpO2 < 90% was consistent for both tests (κ = 0.82). 1STST was superior to diffusing capacity for carbon monoxide in detecting desaturation during the 6MWT. These findings were similarly stratified according to performance status or dyspnea scale. The 1STST can easily measure exertional desaturation in ILD patients with normal resting blood oxygen levels and is an alternative to the 6MWT.
Xor-And-Inverter Graphs for Quantum Compilation
Authors: Meuli Giulia , Soeken Mathias , De Micheli Giovanni
Published: January 2022

Quantum compilation is the task of translating a high-level description of a quantum algorithm into a sequence of low-level quantum operations. We propose and motivate the use of Xor-And-Inverter Graphs (XAG) to specify Boolean functions for quantum compilation. We present three different XAG-based compilation algorithms to synthesize quantum circuits in the Clifford + T library, hence targeting fault-tolerant quantum computing. The algorithms are designed to minimize relevant cost functions, such as the number of qubits, the T-count, and the T-depth, while allowing the flexibility of exploring different solutions. We present novel resource estimation results for relevant cryptographic and arithmetic benchmarks. The achieved results show a significant reduction in both T-count and T-depth when compared with the state-of-the-art.
Metabolomic profiling to detect different forms of beef fraud using rapid evaporative ionisation mass spectrometry (REIMS)
Authors: Robson Kelsey , Birse Nicholas , Chevallier Olivier , Elliott Christopher
Published: January 2022

Organic food fraud is a significant challenge in the food testing sector—high price premiums, ease of access to produce to be relabelled and difficulties in developing testing strategies that can detect such frauds make organic foods particularly attractive and thus highly vulnerable to fraud. Samples of conventional and organic cattle taken across meat plants in Ireland and the United Kingdom, consisting of the neck (supraspinatus), rump (gluteus), and shin (flexor carpi radialis) regions of the carcass were analysed using a high resolution time-of-flight based rapid evaporative ionisation mass spectrometry (REIMS) system. The resulting untargeted lipidomic data (m/z 600–1000) was used to generate PCA-LDA models for production system and for muscle type, for these models, it was found that the production system model could differentiate organic from conventional beef with an accuracy of 84%, whilst the muscle type model could identify the cut of meat with a 98% accuracy; additionally, samples can be assessed against multiple models simultaneously, reducing analysis time and sample numbers. The use of REIMS showed considerable promise in its ability to detect different forms of meat fraud; its accuracy in differentiating organic from conventional beef is superior to stable isotope ratio mass spectrometry, with the added advantages of substantially shorter analysis times and lower sample analysis costs. The ability to rapidly confirm the cut of meat also demonstrates the potential of REIMS to concurrently determine multiple aspects of beef authenticity in a close to real time analysis.
The year that shaped the outcome of the OspA vaccine for human Lyme disease
Authors: Dattwyler Raymond J. , Gomes-Solecki Maria
Published: January 2022

The expansion of Lyme borreliosis endemic areas and the corresponding increase of disease incidence have opened the possibility for greater acceptance of a vaccine. In this perspective article, we discuss the discovery of outer surface protein A (OspA) ofB. burgdorferi, and the subsequent pre-clinical testing and clinical trials of a recombinant OspA vaccine for human Lyme disease. We also discuss in detail the open public hearings of the FDA Lyme disease vaccine advisory panel held in 1998 where concerns of molecular mimicry induced autoimmunity to native OspA were raised, the limitations of those studies, and the current modifications of recombinant OspA to develop a multivalent subunit vaccine for Lyme disease.
Histopathological whole slide image dataset for classification of treatment effectiveness to ovarian cancer
Authors: Wang Ching-Wei , Chang Cheng-Chang , Khalil Muhammad Adil , Lin Yi-Jia , Liou Yi-An , Hsu Po-Chao , Lee Yu-Ching , Wang Chih-Hung , Chao Tai-Kuang
Published: January 2022

Ovarian cancer is the leading cause of gynecologic cancer death among women. Regardless of the development made in the past two decades in the surgery and chemotherapy of ovarian cancer, most of the advanced-stage patients are with recurrent cancer and die. The conventional treatment for ovarian cancer is to remove cancerous tissues using surgery followed by chemotherapy, however, patients with such treatment remain at great risk for tumor recurrence and progressive resistance. Nowadays, new treatment with molecular-targeted agents have become accessible. Bevacizumab as a monotherapy in combination with chemotherapy has been recently approved by FDA for the treatment of epithelial ovarian cancer (EOC). Prediction of therapeutic effects and individualization of therapeutic strategies are critical, but to the authors’ best knowledge, there are no effective biomarkers that can be used to predict patient response to bevacizumab treatment for EOC and peritoneal serous papillary carcinoma (PSPC). This dataset helps researchers to explore and develop methods to predict the therapeutic effect of patients with EOC and PSPC to bevacizumab.
Classification of 74 facial emoji’s emotional states on the valence-arousal axes
Authors: Kutsuzawa Gaku , Umemura Hiroyuki , Eto Koichiro , Kobayashi Yoshiyuki
Published: January 2022

Emojis are frequently used by people worldwide as a tool to express one’s emotional states and have recently been considered for assessment in research. However, details regarding the ways in which they correspond to human emotional states remain unidentified. Thus, this study aimed to understand how emojis are classified on the valence and arousal axes and to examine the relationship between the former and human emotional states. In an online survey involving 1082 participants, a nine-point scale was employed to evaluate the valence and arousal levels of 74 facial emojis. Results from the cluster analysis revealed these emojis to be categorized into six different clusters on the two axes of valence and arousal. Further, the one-way analysis of variance indicated that these clusters have six valence and four arousal levels. From the results, each cluster was interpreted as (1) a strong negative sentiment, (2) a moderately negative sentiment, (3) a neutral sentiment with a negative bias, (4) a neutral sentiment with a positive bias, (5) a moderately positive sentiment, and (6) a strong positive sentiment. Therefore, facial emojis were found to comprehensively express the human emotional states.
Three-dimensional gravity modelling of a Quaternary overdeepening fill in the Bern area of Switzerland discloses two stages of glacial carving
Authors: Bandou D. , Schlunegger F. , Kissling E. , Marti U. , Schwenk M. , Schläfli P. , Douillet G. , Mair D.
Published: January 2022

The geometry of glacial overdeepenings on the Swiss Plateau close to Bern was inferred through a combination of gravity data with a 3D gravity modelling software. The target overdeepenings have depths between 155 and > 270 m and widths between 860 and 2400 m. The models show incisions characterized by U-shaped cross-sectional geometries and steep to over-steepened lateral flanks. Existing stratigraphic data reveals that the overdeepenings were formed and then filled during at least two glacial stages, which occurred during the Last Glacial Maximum (LGM) within the Marine Isotope Stage (MIS) 2, and possibly MIS 6 or before. The U-shaped cross-sectional geometries point towards glacial erosion as the main driver for the shaping of the overdeepenings. The combination of the geometries with stratigraphic data suggests that the MIS 6 (or older) glaciers deeply carved the bedrock, whereas the LGM ice sheet only widened the existing valleys but did not further deepen them. We relate this pattern to the different ice thicknesses, where a thicker MIS 6 ice was likely more powerful for wearing down the bedrock than a thinner LGM glacier. Gravity data in combination with forward modelling thus offers robust information on the development of a landscape formed through glaciers.
Method for evaluating roughness and valley areas coefficients of surfaces acquired by laser scanner
Authors: Tonietto Leandro , Arnold Daiana Cristina Metz , de Oliveira Valéria Costa , Menegotto Camila Werner , Grondona Atilio Efrain Bica , Costa Cristiano André da , Veronez Mauricio Roberto , de Souza Kazmierczak Claudio , Gonzaga Luiz
Published: January 2022

The quantitative determination of average roughness parameters, from the determination of height variations of the surface points, is frequently used to estimate the adhesion between an adhesive and the surface of a substrate. However, to determine the interaction between an adhesive and a surface of a heterogeneous material, such as a red ceramic, it is essential to define other roughness parameters. This work proposes a method for determining the roughness of red ceramic blocks from a three-dimensional evaluation, with the objective of estimating the contact area that the ceramic substrate can provide for a cementitious matrix. The study determines the average surface roughness from multiple planes and proposes the adoption of 2 more roughness parameters, the valley area index and the average valley area. The results demonstrate that there are advantages in using the proposed multiple plane method for roughness computation and that the valley area parameters are efficient to estimate the extent of adhesion between the materials involved.
Effects of Acanthus ebracteatus Vahl. extract and verbascoside on human dermal papilla and murine macrophage
Authors: Wisuitiprot Vanuchawan , Ingkaninan Kornkanok , Chakkavittumrong Panlop , Wisuitiprot Wudtichai , Neungchamnong Nitra , Chantakul Ruttanaporn , Waranuch Neti
Published: January 2022

Androgenic alopecia is a common type of hair loss, usually caused by testosterone metabolism generating dihydrotestosterone and hair follicular micro-inflammation. These processes induce dermal papilla cells to undergo apoptosis. Currently approved effective medications for alopecia are Finasteride, an oral 5α-reductase inhibitor, Minoxidil, a topical hair growth promoter, and Diclofenac, an anti-inflammatory agent, all of which, however, have several adverse side effects. In our study, we showed the bioactivity of Acanthus ebracteatus Vahl. (AE) extract performed by 95% ethanol, and verbascoside (VB), a biomarker of AE extract. Both AE extract and VB were studied for their effects on dermal papilla cell viability and the cell cycle by using MTT assay and flow cytometry. The effect of an anti-inflammatory activity of AE extract and VB on IL-1β, NO, and TNF-α, released from LPS induced RAW 264.7 cells, and IL-1α and IL-6 released from irradiated dermal papilla cells were detected using ELISA technique. The preventive effect on dermal papilla cell apoptosis induced by testosterone was determined by MTT assay. In controlled in vitro assays it was found that AE extract and VB at various concentrations induced dermal papilla cell proliferation which was indicated by an increase in the number of cells in the S and G2/M phases of the cell cycle. AE extract at 250 µg/mL concentration or VB at 62.50 µg/mL concentration prevented cell apoptosis induced by testosterone at a statistically significant level. In addition, both AE extract and VB greatly inhibited the release of pro-inflammatory cytokines from RAW 264.7 and dermal papilla cells. The release of IL-1β, TNF-α, and NO from RAW 264.7 cells, as well as IL-1α and IL-6 from dermal papilla cells, was also diminished by AE extract 250 µg/mL and VB 125 µg/mL. Our results indicate that AE extract and VB are promising ingredients for anti-hair loss applications. However, further clinical study is necessary to evaluate the effectiveness of AE extract and VB as treatment for actual hair loss.
Serum neurofilament indicates that DBS surgery can cause neuronal damage whereas stimulation itself does not
Authors: Frank Anika , Bendig Jonas , Schniewind Iñaki , Polanski Witold H. , Sobottka Stephan B. , Reichmann Heinz , Akgün Katja , Ziemssen Tjalf , Klingelhoefer Lisa , Falkenburger Björn H.
Published: January 2022

Deep brain stimulation (DBS) is a potent symptomatic therapy for Parkinson’s disease, but it is debated whether it causes or prevents neurodegeneration. We used serum neurofilament light chain (NFL) as a reporter for neuronal damage and found no difference between 92 patients with chronic STN-DBS and 57 patients on best medical treatment. Serum NFL transiently increased after DBS surgery whereas the initiation of STN stimulation did not affect NFL levels, suggesting that DBS surgery can be associated with neuronal damage whereas stimulation itself is not.
Triple-negative expression (ALDH1A1-/CD133-/mutant p53-) cases in lung adenocarcinoma had a good prognosis
Authors: Yamashita Naoki , So Tetsuya , Miyata Takeaki , Yoshimatsu Takashi , Nakano Ryuji , Oyama Tsunehiro , Matsunaga Wataru , Gotoh Akinobu
Published: January 2022

Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells because of their capacity for self-renewal. Aldehyde dehydrogenase1A1 (ALDH1A1) and CD133 are promising candidate of CSC markers in non-small cell lung cancer (NSCLC). Furthermore, TP53 is frequently mutated in lung cancer, and the loss of its function is associated with malignant characteristics. However, the relationship between CSCs and mutant p53 in lung adenocarcinoma is not well-established. We examined the expression of ALDH1A1, CD133, and mutant p53 in lung adenocarcinoma patients and conducted a clinicopathological study. Triple-negative cases without ALDH1A1, CD133, and mutant p53 expression in lung adenocarcinoma were shown to have a much better prognosis than others. Our present results suggest that detection of CSC markers and mutant p53 by immunohistochemical staining may be effective in therapeutic strategies for lung adenocarcinoma.