bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and management evaluation of the nubian sandstone aquifer in Tazerbo wellfield of the Libyan man-made river project
Authors: Hamad Salah , Saaid Fawzi
Published: May 2022

Tazerbo water wellfield, located in southeast Libya, was constructed as part of the first stage for the Man-Made River Project (Eastern System) during 1995–2003. A group of land subsidence forms was discovered approximately 30 km north of the wellfield two years after production, which began in March 2004. The wellfield production rate is only about one-third of its designed capacity. In addition to the land subsidence, there is a problem with the natural groundwater quality represented by high iron and manganese concentrations. This research aims to characterize the aquifer system and assess the current condition of the wellfield since its operation in 2004 in terms of groundwater quality and quantity. It further evaluates current groundwater management practices. The geographic information system was used to map hydrogeologic data of drilled water wells and groundwater monitoring data from 2003 to 2019. The aquifer system characterization showed that the exploited aquifer has excellent hydraulic properties and promising potential for future groundwater utilization. The measured drawdown during 2019 shows a maximum decline of 28 m. Moreover, the average water production is about 322,270 m3/ day, equivalent to 32% of the total abstraction proposed to the end of the year 2020 of about 1907 million m3. As far as Groundwater quality is concerned, there has been no change in water quality since the beginning of abstraction. This research indicates that current policy and institutional approaches and practices promote the optimum management of the wellfield’s water resources.
Evaluation of WMS model in basins without statistical data in southwestern Iran using Dicken's experimental method (case study: Kuhgel Basin of Khuzestan Province)
Authors: Hoseini Yaser
Published: May 2022

Floods are important in studies related to water resources utilization, dam construction, basin management and hydrological studies. Therefore, to a large extent, the accuracy of these studies and the safety of water facilities depends on the flood study methods. The aim of this study was to investigate the WMS model in determining the maximum flood discharge in three sub-basins with areas of 10.3, 1.5 and 7.3 square kilometers in the Kuhgel region located in southwest of Iran. Comparing the results of the model with the results of the Dicken's experimental method in the region showed that the maximum flood discharge and flood volume estimated by the WMS model are well consistent with the values of the Dicken's experimental method. Therefore, the relative error percentage index, root-mean-square error and Nash–Sutcliffe coefficient of the model were calculated equal to 6.12, 0.51 and 0.82, respectively. The results also revealed that the mean of model estimates was approximately 0.16% higher than Dicken's experimental method. Based on Student's t-test, the difference between the model values and Dicken's experimental method was not significant at the level of one percent. The results show that the WMS model simulates flood values with appropriate accuracy for basins with no statistical data in southwest of Iran. Due to the high sensitivity of the SCS method in the WMS model to rainfall distribution, rainfall analysis in the study area is necessary to achieve the desired results and the rainfall distribution and its time distribution should be as close as possible to the actual values in the region.
Automatic Classification of Bloodstains with Deep Learning Methods
Authors: Bergman Tommy , Klöden Martin , Dreßler Jan , Labudde Dirk
Published: May 2022

The classification of detected bloodstains into predetermined categories is a crucial component of the so-called bloodstain pattern analysis. As in other forensic disciplines, deep learning methods may help to reduce human subjectivity within this process, may increase the classification accuracy, shorten the calculation time and thus, enable high-throughput analysis. In this work, an approach is presented in which a convolutional neural network (Inception v3) was trained from 965 drip stains (passive origin) and 1595 blood spatters (active origin). The trained CNN was evaluated with a test data set consisting of 366 images of drip stains and blood spatters. The success rate was 99.73% which suggests that neural networks could also be used to automatically classify other classes of bloodstain patterns to speed up the investigation process in the future.
DNA sequence features underlying large-scale duplications and deletions in human
Authors: Kołomański Mateusz , Szyda Joanna , Frąszczak Magdalena , Mielczarek Magda
Published: May 2022

Copy number variants (CNVs) may cover up to 12% of the whole genome and have substantial impact on phenotypes. We used 5867 duplications and 33,181 deletions available from the 1000 Genomes Project to characterise genomic regions vulnerable to CNV formation and to identify sequence features characteristic for those regions. The GC content for deletions was lower and for duplications was higher than for randomly selected regions. In regions flanking deletions and downstream of duplications, content was higher than in the random sequences, but upstream of duplication content was lower. In duplications and downstream of deletion regions, the percentage of low-complexity sequences was not different from the randomised data. In deletions and upstream of CNVs, it was higher, while for downstream of duplications, it was lower as compared to random sequences. The majority of CNVs intersected with genic regions — mainly with introns. GC content may be associated with CNV formation and CNVs, especially duplications are initiated in low-complexity regions. Moreover, CNVs located or overlapped with introns indicate their role in shaping intron variability. Genic CNV regions were enriched in many essential biological processes such as cell adhesion, synaptic transmission, transport, cytoskeleton organization, immune response and metabolic mechanisms, which indicates that these large-scaled variants play important biological roles.
Mechanic model of water-based boundary lubricated contact based on surface force effects
Authors: Fang Yanfei , Ma Liran
Published: May 2022

In water-based boundary lubrication regime, the contact gaps (or boundary lubricated film thickness) and surface pressure distribution must be determined to really understand the boundary lubricated contact mechanism. However, the accurate determination of these parameters is limited. In this study, a mechanical model based on boundary lubricated contact involving surface force effects is developed. The surface force distribution characteristics, normal force vs. central film thickness curve, and macroscale water-based boundary lubricated contact are investigated numerically. The results show that hydration directly affects surface force interaction. The accurate boundary lubricated film thickness and surface pressure distribution can be obtained using this model in point contact. Furthermore, the mechanism of macroscale water- based liquid boundary lubricated contact is investigated, in which a water-based boundary lubricated film is formed under appropriate operating conditions based on surface force effects during running-in. This study can reveal the water-base boundary lubricated contact behavior and the carrying capacity of the surface force effect, and provides important design guidance for the surface force effect to achieve liquid superlubricity in water-based boundary lubricated contacts.
Malignant mixed mullerian tumor: A case report about a uterine Tumor's case
Authors: Morgan Emmanuel D. , Okecha Tony , Yahaya James J. , Othieno Emmanuel
Published: May 2022

ABSTRACT

Introduction:

Malignant mixed Mullerian tumor (MMMT) is an exceedingly rare and aggressive tumor which occurs predominantly in postmenopausal women though it has been reported rarely in premenopausal women.

Case presentation:

A 54-year old nulliparous postmenopausal female presented with a 3-month history of vaginal bleeding, mild lower abdominal pain and weight loss. Ultrasound revealed markedly enlarged uterus with a hyper-echoic solid and cystic mass and a right adnexal complex mass. Total abdominal hysterectomy and bilateral salpingioopherectomy were done. Histopathological features were consistent with MMMT. The patient is currently stable after 6 cycles of adjuvant chemotherapy which consisted of paclitaxel and carboplatin.

Clinical discussion:

MMMT of the uterus is rare, high-grade neoplasms comprising only 1–2% of uterine cancers and 3–5% of all uterine malignancies. This tumor may arise in the ovaries, fallopian tubes and vagina. Histologically, MMMT is a biphasic tumor composed of both epithelial (carcinoma) elements and mesenchymal (sarcoma) elements; though, which component is responsible for the tumor's aggressive biological behavior remains undetermined.

Conclusion:

MMMT is a rare and aggressive tumor which is commonly seen in postmenopausal women with high rate of recurrence therefore, Radical surgery and close follow-up is mandatory since the role of chemoradiotherapy remains unclear in the management of patients with this tumor. Both stage of the tumor and myometrial invasion are considered as potential prognostic factors.

Highlights
Rules of Origin in International Trade
Authors: Inama Stefano
Published: May 2022

This book provides comprehensive, in-depth analysis of the different sets of rules of origin adopted by major trading partners and worldwide, as well as efforts to establish multilateral rules at WTO and WCO. It discusses the status of non-preferential as well as preferential rules of origin in international trade, their evolution during the last decades and their tendencies and future. With its multidisciplinary approach, this book's contents provide comparative analysis of the relevant legal and economic features of different rules origin compilation sets, reviewing their drafting differences and their implications and impact on the economic and industrial environments. This edition has been updated and expanded to include the latest developments on rules of origin at multilateral level in WTO and WCO and on rules of origin in recent FTAs. Drawing from his thirty years of experience, Stefano Inama provides insights from trade negotiations along with practical tools for policy makers and practitioners, orientation for the private sector and analytical tools for researchers.
Testing the Drugs’ Sentencing Guidelines: A Comparison between England and Wales and Hong Kong
Authors: Cheng Kevin Kwok-Yin , Ri Sayaka , Pushkarna Natasha
Published: May 2022

In the era of sentencing guidelines, the punishment for traffickers is primarily based on the offenders’ culpability and the drug weight. Existing literature tend to focus on the issue of proportionality as it relates to the roles and culpability of offenders. However, little attention has been drawn to the quantity of drugs. England and Wales have incorporated offender roles into their sentencing guidelines, while Hong Kong uses drug tariffs strictly based on drug weight to calculate the starting point of a sentence. Using a novel equation called ‘the arithmetic starting point of sentence’, this study examines the starting sentence based on each gram of drugs by undertaking a comparative analysis of the respective jurisdictions. The results show that both jurisdictions have adopted sentencing guidelines that exhibit a logarithmic curve. This implies that the scale used to measure the quantity of drugs is disproportionate, penalising smaller quantities more harshly than larger quantities.
Evidence-based practice strategies for faculty professional development in clinical translational research at Institutional Development Award (IDeA) state institutions in the Mountain West
Authors: Kataoka-Yahiro Merle R. , Myaskovsky Larissa , Dagda Ruben K. , Sood Akshay , Conway Kathrene , Lopez Joseph Guerrero , Burge Mark R. , Sy Francisco S.
Published: May 2022

The Mountain West Clinical Translational Research – Infrastructure Network (MW CTR-IN), established in 2013, is a research network of 13 university partners located among seven Institutional Development Award (IDeA) states targeting health disparities. This is an enormous undertaking because of the size of the infrastructure network (encompassing a third of the US landmass and spanning four time zones in predominantly rural and underserved areas, with populations that have major health disparities issues). In this paper, we apply the barriers, strategies, and metrics to an adapted educational conceptual model by Fink (2013). Applying this model, we used four tailored approaches across this regional infrastructure network to: (1) assess individual faculty specific needs, (2) reach out and engage with faculty, (3) provide customized services to meet the situational needs of faculty, and (4) utilize a “closed communication feedback loop” between Professional Development (PD) core and MW CTR-IN faculty within the context of their home institutional environment. Summary statement results from participating faculty show that these approaches were positive. Grounded in best educational practice approaches, we have an opportunity to refine and build from this sound foundation with implications for future use in other CTR-IN networks and institutions in the IDeA states.
The zero mass problem for Klein-Gordon equations: quadratic null interactions
Authors: Dong Shijie
Published: May 2022

We study in

$\mathbb {R}^{3+1}$

a system of nonlinearly coupled Klein-Gordon equations under the null condition, with (possibly vanishing) mass varying in the interval

$[0, 1]$

. Our goal is three-fold, which extends the results in the earlier work of [5, 3]: 1) we want to establish the global well-posedness result to the system that is uniform in terms of the mass parameter (i.e., the smallness of the initial data is independent of the mass parameter); 2) we want to obtain a unified pointwise decay result for the solution to the system, in the sense that the solution decays more like a wave component (independent of the mass parameter) in a certain range of time, while the solution decays as a Klein-Gordon component with a factor depending on the mass parameter in the other part of the time range; 3) the solution to the Klein-Gordon system converges to the solution to the corresponding wave system in a certain sense when the mass parameter goes to 0. In order to achieve these goals, we will rely on both the flat and hyperboloidal foliation of the spacetime and prove a mass-independent

$L^2$

–type energy estimate for the Klein-Gordon equations with possibly vanishing mass. In addition, the case of the Klein-Gordon equations with certain restricted large data is discussed.
An insulating plate drifting over a thermally convecting fluid: the thermal blanket effect on plume motion and the emergence of a unidirectionally moving mode
Authors: Mao Yadan
Published: May 2022

Floating rather stably above the convective mantle, continents exert a thermal blanket effect on the mantle by locally accumulating heat and altering the flow structure, which in turn affect continent motion. This thermal-mechanic feedback has been captured by a simplified model―a thermally insulating plate floating freely over a bottom-heated convecting fluid. Previous studies have revealed that, as plate size increases, plate motion transitions from long-term stagnancy over cold downwelling to short-term stagnancy over hot upwelling, termed stagnant modes (SMs) I and II, respectively, and eventually to a unidirectionally moving mode (UMM) with no stagnancy. During SM I/II, the adjacent hot/cold plumes are observed to move toward/away from the plate. The present study quantifies these plume motions through analysis on a partially insulated loop model established for SM I and SM II, respectively. The model predictions are well verified by results of numerical simulation. Moreover, the dominant frequency of plate speed is shown to increase linearly with plate size, with an abrupt jump as the coupling mode transitions from SM I to SM II. This suggests that the enhanced thermal blanket effect with plate size enables an increasingly fast feedback between the slowdown of a plate and the strengthening of hot upwelling which boosts plate motion. When plate motion is boosted before it stops, the UMM emerges. The predicted critical plate size for the UMM is well validated by simulation results. Geological implications of the results for continent motion, continent–mantle coupling and particularly the migration of plume and subduction sites are discussed.
A layer of yield-stress material on a flat plate that moves suddenly
Authors: Hinton Edward M. , Collis Jesse F. , Sader John E.
Published: May 2022

The flow of an unbounded Newtonian fluid above a flat solid plate, set into motion suddenly with uniform velocity, is a canonical problem investigated by Stokes (On the effect of the internal friction of fluids on the motion of pendulums, Trans. Camb. Phil. Soc., vol. 9, 1851) and Rayleigh (Lond. Edinb. Dubl. Philos. Mag. J. Sci., vol. 21, issue 126, 1911, pp. 697–711). We tackle the same problem but with the fluid replaced by a yield-stress material of finite height with a free surface; the latter ensures both yielded (fluid-like) and rigid behaviour. The interface between the yielded and rigid regions – the so-called ‘yield surface’ – always emerges from the plate at a rate faster than that for momentum diffusion. The rigid region, adjacent to the free surface, is accelerated by the constant yield stress acting at this yield surface. As the velocity of this region increases following start-up, its acceleration climaxes and subsequently diminishes. In this latter period, the thickness of the rigid region increases owing to relaxation of the velocity gradients and the stress. The yield surface eventually collides with the plate in finite time, after which the entire material moves in concert with the plate as a rigid body. Analytical and numerical results are presented that can form the basis for practical applications. This includes the development of a ‘rheological microscope’ to directly detect and measure the yield stress. The analysis focuses on exploring the flow physics of a Bingham material. This is shown to be similar to that of a general Herschel–Bulkley material with shear-thinning or shear-thickening rheology.
Validating the Applicability of Bayesian Inference with Surname and Geocoding to Congressional Redistricting
Authors: DeLuca Kevin , Curiel John A.
Published: May 2022

Ensuring descriptive representation of racial minorities without packing minorities too heavily into districts is a perpetual difficulty, especially in states lacking voter file race data. One advance since the 2010 redistricting cycle is the advent of Bayesian Improved Surname Geocoding (BISG), which greatly improves upon previous ecological inference methods in identifying voter race. In this article, we test the viability of employing BISG to redistricting under two posterior allocation methods for race assignment: plurality versus probabilistic. We validate these methods through 10,000 redistricting simulations of North Carolina and Georgia’s congressional districts and compare BISG estimates to actual voter file racial data. We find that probabilistic summing of the BISG posteriors significantly reduces error rates at the precinct and district level relative to plurality racial assignment, and therefore should be the preferred method when using BISG for redistricting. Our results suggest that BISG can aid in the construction of majority-minority districts during the redistricting process.
Isoleucine stimulates mTOR and SREBP-1c gene expression for milk synthesis in mammary epithelial cells through BRG1-mediated chromatin remodelling
Authors: Hao Qi , Wang Zhe , Wang Lulu , Han Meihong , Zhang Minghui , Gao Xuejun
Published: May 2022

Several amino acids can stimulate milk synthesis in mammary epithelial cells (MEC); however, the regulatory role of isoleucine (Ile) and underlying molecular mechanism remain poorly understood. In this study, we aimed to evaluate the regulatory effects of Ile on milk protein and fat synthesis in MEC and reveal the mediation mechanism of Brahma-related gene 1 (BRG1) on this regulation. Ile dose dependently affected milk protein and fat synthesis, mechanistic target of rapamycin (mTOR) phosphorylation, sterol regulatory element binding protein 1c (SREBP-1c) expression and maturation, and BRG1 protein expression in bovine MEC. Phosphatidylinositol 3 kinase (PI3K) inhibition by LY294002 treatment blocked the stimulation of Ile on BRG1 expression. BRG1 knockdown and gene activation experiments showed that it mediated the stimulation of Ile on milk protein and fat synthesis, mTOR phosphorylation, and SREBP-1c expression and maturation in MEC. ChIP-PCR analysis detected that BRG1 bound to the promoters of mTOR and SREBP-1c, and ChIP-qPCR further detected that these bindings were increased by Ile stimulation. In addition, BRG1 positively regulated the binding of H3K27ac to these two promoters, while it negatively affected the binding of H3K27me3 to these promoters. BRG1 knockdown blocked the stimulation of Ile on these two gene expressions. The expression of BRG1 was higher in mouse mammary gland in the lactating period, compared with that in the puberty or dry period. Taken together, these experimental data reveal that Ile stimulates milk protein and fat synthesis in MEC via the PI3K-BRG1-mTOR/SREBP-1c pathway.
Association between pre-conceptional carbohydrate quality index and the incidence of gestational diabetes: the SUN cohort study
Authors: Fernández-González Elena , Martínez-González Miguel Á. , Bes-Rastrollo Maira , Suescun-Elizalde David , Basterra-Gortari Francisco Javier , Santiago Susana , Gea Alfredo
Published: May 2022

The aim of the study was to investigate the association between pre-gestational carbohydrate quality index (CQI) and the incidence of gestational diabetes mellitus (GDM). Data from the ‘Seguimiento Universidad de Navarra’ (SUN) cohort were used, which includes 3827 women who notified at least one pregnancy between December 1999 and December 2019. We used a validated semi-quantitative 136-item FFQ to evaluate dietary exposures at baseline and at 10-year follow-up. The CQI was defined by four criteria: glycaemic index, whole-grain/total-grain carbohydrate, dietary fibre intake and solid/total carbohydrate ratio. We fitted generalised estimating equations with repeated measurements of the CQI to assess its relationship with incident GDM. A total of 6869 pregnancies and 202 new cases of incident GDM were identified. The inverse association between the global quality of carbohydrate and the development of GDM was not statistically significant: OR the highestv. the lowest CQI category: 0·67, 95 % CI (0·40, 1·10),Pfor trend= 0·10. Participants at the highest CQI category and with daily carbohydrate amounts ≥50 % of total energy intake had the lowest incidence of GDM (OR = 0·29 (95 % CI (0·09, 0·89)) compared with those with the lowest quality (lowest CQI) and quantity (≤40 %). Further studies are needed to overcome the limitations of our study. Those studies should jointly consider the quality and the quantity of dietary carbohydrates, as the quality might be of importance, especially in women with a higher intake of carbohydrates.
REBELLION ON THE SAUDI PERIPHERY: MODERNITY, MARGINALIZATION, AND THE SHIA UPRISING OF 1979
Authors: Jones Toby Craig
Published: May 2022

For seven dramatic days in late November 1979, bloody street violence between state security forces and thousands of frustrated Shiites rocked the Eastern Province of Saudi Arabia. Sparked by the Saudi regime's brutal repression of those peacefully celebrating

Ashura—the annual mourning of the martyrdom of Imam Hussein—the fury resulted in an unknown number of dead and wounded. Among the destruction, demonstrators burned the British bank in Qatif as well as the offices of the Saudia National Airline. They destroyed state-owned vehicles, attacked police, raided the coast guard office in the village of al-

Awamiyya, seized weapons from soldiers, and even occupied the old city in downtown Qatif, from which they held off the Saudi military for days. One report relates that a group even burned a toy store owned by a government official. Women as well as men marched in anger. The security forces, which included 20,000 Saudi National Guard, cordoned off the major roadways, particularly those in Qatif, Sayhat, and Safwa to localize the protest, control the flow of information, as well as to prevent nearby oil facilities from being destroyed. Reports swirled that soldiers fired on virtually any public gathering of people, including at least one funeral procession in Safwa, forcing the mourners to flee and abandon the corpse in the street. State and hospital officials refused to release other bodies from the morgue for burial until the uproar quieted, leveraging the dead as blackmail. The National Guard relied on the heavy firepower of helicopter gun ships for crowd control, turning the area into a deadly conflict zone characterized by terror, hostility, and fear.
Intestinal parasites in the Neolithic population who built Stonehenge (Durrington Walls, 2500 BCE)
Authors: Mitchell Piers D. , Anastasiou Evilena , Whelton Helen L. , Bull Ian D. , Parker Pearson Mike , Shillito Lisa-Marie
Published: May 2022

Durrington Walls was a large Neolithic settlement in Britain dating around 2500 BCE, located very close to Stonehenge and likely to be the campsite where its builders lived during its main stage of construction. Nineteen coprolites recovered from a midden and associated pits at Durrington Walls were analysed for intestinal parasite eggs using digital light microscopy. Five (26%) contained helminth eggs, 1 with those of fish tapeworm (likelyDibothriocephalus dendriticus) and 4 with those of capillariid nematodes. Analyses of bile acid and sterol from these 5 coprolites show 1 to be of likely human origin and the other 4 to likely derive from dogs. The presence of fish tapeworm reveals that the Neolithic people who gathered to feast at Durrington Walls were at risk of infection from eating raw or undercooked freshwater fish. When the eggs of capillariids are found in the feces of humans or dogs it normally indicates that the internal organs (liver, lung or intestines) of animals with capillariasis have been eaten, and eggs passed through the gut without causing disease. Their presence in multiple coprolites provides new evidence that internal organs of animals were consumed. These novel findings improve our understanding of both parasitic infection and dietary habits associated with this key Neolithic ceremonial site.
General overview of the current status of human foodborne trematodiasis
Authors: Chai Jong-Yil , Jung Bong-Kwang
Published: May 2022

Foodborne trematodes (FBT) of public health significance include liver flukes (Clonorchis sinensis, Opisthorchis viverrini, O. felineus, Fasciola hepaticaandF. gigantica), lung flukes (Paragonimus westermaniand several otherParagonimusspp.) and intestinal flukes, which include heterophyids (Metagonimus yokogawai, Heterophyes nocensandHaplorchis taichui), echinostomes (Echinostoma revolutum, Isthmiophora hortensis, Echinochasmus japonicusandArtyfechinostomum malayanum) and miscellaneous species, includingFasciolopsis buskiandGymnophalloides seoi. These trematode infections are distributed worldwide but occur most commonly in Asia. The global burden of FBT diseases has been estimated at about 80 million, however, this seems to be a considerable underestimate. Their life cycle involves a molluscan first intermediate host, and a second intermediate host, including freshwater fish, crustaceans, aquatic vegetables and freshwater or brackish water gastropods and bivalves. The mode of human infection is the consumption of the second intermediate host under raw or improperly cooked conditions. The major pathogenesis ofC. sinensisandOpisthorchisspp. infection includes inflammation of the bile duct which leads to cholangitis and cholecystitis, and in a substantial number of patients, serious complications, such as liver cirrhosis and cholangiocarcinoma, may develop. In lung fluke infections, cough, bloody sputum and bronchiectasis are the most common clinical manifestations. However, lung flukes often migrate to extrapulmonary sites, including the brain, spinal cord, skin, subcutaneous tissues and abdominal organs. Intestinal flukes can induce inflammation in the intestinal mucosa, and they may at times undergo extraintestinal migration, in particular, in immunocompromised patients. In order to control FBT infections, eating foods after proper cooking is strongly recommended.
Feasibility study to characterize price and reimbursement decision-making criteria for the inclusion of new drugs in the Spanish National Health System: the cefiderocol example
Authors: Calleja Miguel Ángel , Badia Xavier
Published: May 2022

Objectives

The reimbursement of medicines by the Spanish National Health System (NHS) is based on a set of criteria included in the Royal Legislative Decree 1/2015 (RDL 1/2015). The Interministerial Committee on Pricing of Medicines and Healthcare Products (CIPM) is responsible for the final price and reimbursement (P&R) decision, including on its resolutions the criteria listed in the law by which the reimbursement of a drug is approved or denied. Nevertheless, the information behind its reasoning is not provided. The present study aims to characterize the P&R criteria of the RDL 1/2015 through criteria definitions from other countries to improve the P&R evaluation in Spain.

Results

A multidisciplinary experts panel with relevant experience in drug evaluation and decision making at national, regional, and local level in Spain was selected for this study. A literature review to characterize the criteria listed in the RDL 1/2015 was performed based on the most relevant and recognized Health Technology Assessment (HTA) agencies in Europe, UK, and Canada. Eventually, a feasibility study was performed to evaluate the novel drug cefiderocol using the characterized criteria, including a reflective discussion of the results.

Conclusions

Consensus was reached among the multidisciplinary experts on the characterization of the criteria set by the law. The feasibility of their application to a new drug was exploratory, notwithstanding it showed the potential to improve the transparency as well as to offer a more structured rationale for the CIPM to evaluate the inclusion of new drugs in the Spanish NHS.
EXTENSION BETWEEN SIMPLE MODULES OF PRO-p-IWAHORI HECKE ALGEBRAS
Authors: Abe Noriyuki
Published: May 2022

We calculate the extension groups between simple modules of pro-p-Iwahori Hecke algebras.
The Heritability of Twinning in Seven Large Historic Pedigrees
Authors: Duffy David L. , Martin Nicholas G.
Published: May 2022

It is widely recognized that dizygotic twinning (DZT) runs in families, but estimates of heritability from twin and family data are remarkably scarce and vary considerably. Here, we traced seven large, sometimes historical, multigeneration pedigrees from West Africans, fin de siècle French Jews, Canadians (two pedigrees), and the French royal family, in which twin births were recorded. We estimated heritability of twinning (of all types) as zygosity information was not available, diluting the true DZT heritability by a third or so. The estimates in the range 8−20% are remarkably consistent across time (8−19 generations) and ethnicities and also consistent with twin and family estimates.
Evidence of Alfvénic Activity in Jupiter's Mid‐To‐High Latitude Magnetosphere
Authors: Lorch C. T. S. , Ray L. C. , Wilson R. J. , Bagenal F. , Crary F. , Delamere P. A. , Damiano P. A. , Watt C. E. J. , Allegrini F.
Published: May 2022

Using a combination of Juno magnetometer and plasma data, we show evidence of Alfvénic turbulence within the mid‐to‐high latitude magnetosphere with sufficient conditions to trigger auroral particle acceleration. We analyze 12 events that, in agreement with theoretical results, are found to be dissipative at the electron inertial scale. Furthermore, these events contain significant Poynting flux in the range ∼0.8–20 mW/m2 at ionospheric altitudes. This is sufficient to generate auroral emissions. We confirm that such events are incompressible, confirming their Alfvénicity, occur at dissipative scales, have intermittent features present and are multifractal in nature. These results illustrate the importance of turbulence in the mid‐to‐high latitudes of Jupiter's magnetosphere as a driver of particle acceleration.
Age and Rate of Accumulation of Metal‐Rich Hydrothermal Deposits on the Seafloor: The Lucky Strike Vent Field, Mid‐Atlantic Ridge
Authors: Sánchez‐Mora Dennis , Jamieson John , Cannat Mathilde , Escartín Javier , Barreyre Thibaut
Published: May 2022

Hydrothermal venting at the Lucky Strike hydrothermal field, located on the Mid‐Atlantic Ridge, is associated with faulting linked to the tectonic dismemberment of a central axial volcano. Radium‐226/Ba dating of hydrothermal barite indicates that hydrothermal venting is at least 6,600 years old, and that Lucky Strike is one of the youngest known vent fields on the Mid‐Atlantic Ridge, which typically have ages exceeding 20 ka. Deposit volume calculations indicate that the total accumulated mass of the hydrothermal deposits on the seafloor at Lucky Strike is ∼1.3 ± 0.2 Mt, and that this mass accumulated at a maximum average rate of 194 ± 28 t/yr. This accumulation rate is comparable to other well characterized mid‐ocean ridge hydrothermal sites, such as TAG and Endeavor, but at Lucky Strike is concentrated within a relatively small area of <2.5 km2.
Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells
Authors: Fan Liang-Liang , Du Ran , Liu Ji-Shi , Jin Jie-Yuan , Wang Chen-Yu , Dong Yi , He Wan-Xia , Yan Ri-Qiang , Xiang Rong
Published: May 2022

Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has previously been shown to play roles in neurodegenerative diseases, but little is known about its function in the kidneys. The aim of the present study was to clarify the roles of RTN3 in chronic kidney disease (CKD) and kidney fibrosis. In this study, RTN3 levels were measured in kidney tissues from healthy controls and CKD or kidney fibrosis patients. An RTN3-null mouse model was generated to explore the pathophysiological roles of RTN3 in the kidneys. The underlying mechanisms were studied in primary proximal tubular epithelial cells and HEK293 cells in vitro. The results showed that (1) a reduction in RTN3 in mice induces CKD and kidney fibrosis; (2) decreased RTN3 expression is found in patients with CKD; (3) RTN3 plays critical roles in regulating collagen biosynthesis and mitochondrial function; and (4) mechanistically, RTN3 regulates these phenotypes by interacting with GC-Rich Promoter Binding Protein 1 (GPBP1), which activates the IGF2-JAK2-STAT3 pathway. Our study indicates that RTN3 might play crucial roles in CKD and kidney fibrosis and that a reduction in RTN3 in the kidneys might be a risk factor for CKD and kidney fibrosis.
ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition—implications for COVID-19
Authors: El-Sayed Moustafa Julia S. , Jackson Anne U. , Brotman Sarah M. , Guan Li , Villicaña Sergio , Roberts Amy L. , Zito Antonino , Bonnycastle Lori , Erdos Michael R. , Narisu Narisu , Stringham Heather M. , Welch Ryan , Yan Tingfen , Lakka Timo , Parker Stephen , Tuomilehto Jaakko , Seow Jeffrey , Graham Carl , Huettner Isabella , Acors Sam , Kouphou Neophytos , Wadge Samuel , Duncan Emma L. , Steves Claire J. , Doores Katie J. , Malim Michael H. , Collins Francis S. , Pajukanta Päivi , Boehnke Michael , Koistinen Heikki A. , Laakso Markku , Falchi Mario , Bell Jordana T. , Scott Laura J. , Mohlke Karen L. , Small Kerrin S.
Published: May 2022

Background

COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain.

Subjects/methods

In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry.

Results

Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 × 10−6), obesity status (P = 4.81 × 10−5), higher serum fasting insulin (P = 5.32 × 10−4), BMI (P = 3.94 × 10−4), and lower serum HDL levels (P = 1.92 × 10−7). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells (P = 4.25 × 10−4) and higher proportion of macrophages (P = 2.74 × 10−5). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression.

Conclusions

Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19.
In the shadow of the laser phantom needle cross: dynamic air-plasma aperture sheds light on terahertz microscopy
Authors: Headland Daniel , Withayachumnankul Withawat
Published: May 2022

Two plasma filaments crossing above the target create a subwavelength window for terahertz microscopy that excludes any subwavelength probe in vicinity.
GLI1 activates pro-fibrotic pathways in myelofibrosis fibrocytes
Authors: Manshouri Taghi , Veletic Ivo , Li Ping , Yin C. Cameron , Post Sean M. , Verstovsek Srdan , Estrov Zeev
Published: May 2022

Bone marrow (BM) fibrosis was thought to be induced exclusively by mesenchymal stromal cells (MSCs). However, we and others found that neoplastic fibrocytes induce BM fibrosis in myelofibrosis (MF). Because glioma-associated oncogene-1 (GLI1), an effector of the Hedgehog pathway, plays a role in the induction of BM fibrosis, we wondered whether GLI1 affects fibrocyte-induced BM fibrosis in MF. Multiplexed fluorescence immunohistochemistry analysis of MF patients’ BM detected high levels of GLI1 in MF fibrocytes compared to MSCs or normal fibrocytes. Immunostaining, RNA in situ hybridization, gene expression analysis, and western immunoblotting detected high levels of GLI1 and GLI1-induced matrix metalloproteases (MMP) 2 and 9 in MF patients BM-derived cultured fibrocytes. Similarly, MF patients’ BM-derived GLI1+ fibrocytes were found in BMs and spleens of MF xenograft mice. GLI1 silencing reduced the levels of MMP2/9, phosphorylated SMAD2/3, and procollagen-I, and knockdown or inhibition of GLI1 decreased fibrocyte formation and induced apoptosis of both fibrocytes and fibrocyte progenitors. Because Janus kinase (JAK)2-induced STAT3 is constitutively activated in MF and because STAT3 induces GLI1 expression, we sought to determine whether STAT3 activates GLI1 in MF fibrocytes. Imaging analysis detected phosphotyrosine STAT3 in MF patients’ BM fibrocytes, and transfection of fibrocytes with STAT3-siRNA or treatment with a JAK1/2 inhibitor ruxolitinib reduced GLI1 and MMP2/9 levels. Chromatin immunoprecipitation and a luciferase assay revealed that STAT3 induced the expression of the GLI1 gene in both MF BM fibrocytes and fibrocyte progenitors. Together, our data suggest that STAT3-activated GLI1 contributes to the induction of BM fibrosis in MF.
Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer
Authors: Zhu Tingjia , Cen Yixuan , Chen Zhuoye , Zhang Yanan , Zhao Lu , Wang Jiaying , Lu Weiguo , Xie Xing , Wang Xinyu
Published: May 2022

Circular RNAs (circRNAs) are critical regulators in the occurrence and development of numerous cancers, in which abnormal autophagy plays a key role. However, the potential involvement of circRNAs in autophagy is largely unknown. Here, we identified the overexpression of circTICRR, a circular RNA, in cervical cancer. In vitro experiments showed that knockdown of circTICRR activated autophagy, and consequently promoted apoptosis and inhibited proliferation in cervical cancer cells, and vice versa. CircTICRR interacted with HuR protein via binding to F287/F289 in the RRM3 domain of HuR, stabilizing GLUD1 mRNA and elevating the level of GLUD1 protein. In vivo experiments revealed that knockdown of circTICRR suppressed the growth of transplanted tumors. An inhibitory peptide specific to the binding site between circTICRR and HuR protein promoted autophagy, induced apoptosis, suppressed proliferation in cervical cancer cells, and inhibited the growth of xenografts. Our findings suggest that circTICRR acts as an oncogene in cervical cancer and the interaction between circTICRR and HuR protein may be a potential target in cervical cancer therapeutics.
Role of magnetostriction on power losses in nanocrystalline soft magnets
Authors: Tsukahara Hiroshi , Imamura Hiroshi , Mitsumata Chiharu , Suzuki Kiyonori , Ono Kanta
Published: May 2022

Soft magnetic materials are key materials for the magnetic cores used in motors and generators. To improve the energy efficiency of magnetic cores, it is important to understand the mechanism of energy loss under oscillating magnetic fields. Here, we clarify the mechanism of energy loss in nanocrystalline soft magnetic materials (NSMMs), which are candidates for energy-efficient magnetic cores. To investigate the energy loss of an NSMM, it is necessary to consider the interaction between the magnetization and the crystal lattice, i.e., magnetostriction. However, the random distributions of crystalline axes in nanocrystals hinder magnetostriction calculation. We developed a micromagnetic simulation program by formulating the effective fields due to magnetostriction in randomly oriented nanocrystallites. We performed micromagnetic simulations of NSMMs under an oscillating magnetic field and found that the magnetic energy of the moving domain wall dissipates into the elastic energy of the crystal lattice through magnetostriction. These results can enable the design of highly energy-efficient NSMMs.
Triplet-radical spin entanglement: potential of molecular materials for high-temperature quantum information processing
Authors: Ma Lin , Chang Jiawei , Chen Qiuyuan , Zou Taoyu , Wu Wei , Wang Hai
Published: May 2022

Recently, spin-bearing molecules have been experimentally demonstrated to have great potential as building blocks for quantum information processing due to their substantial advantages including tunability, portability, and scalability. Here, we propose a theoretical model based on the theory of open quantum systems for spin dynamics in a molecule containing one radical, which can interact with the triplet state arising from another part of the molecule owing to optical excitation and intersystem crossing. With the initial state being a classical mixture of a radical $$\frac{1}{2}$$

1

2

-spin, the exchange interaction between the radical and the triplet produces a spin coherent state, which could potentially be used for a qubit-qutrit quantum entangling gate. Our calculations for the time-resolved electron paramagnetic resonance spectra showed good qualitative agreement with the related experimental results for radical-bearing molecules at high temperature (~77 K, the boiling point of liquid nitrogen). This work therefore lays a solid theoretical cornerstone for optically driven quantum gate operations in radical-bearing molecular materials, aiming toward high-temperature quantum information processing.
Holocene melting of the West Antarctic Ice Sheet driven by tropical Pacific warming
Authors: Sproson Adam D. , Yokoyama Yusuke , Miyairi Yosuke , Aze Takahiro , Totten Rebecca L.
Published: May 2022

The primary Antarctic contribution to modern sea-level rise is glacial discharge from the Amundsen Sea sector of the West Antarctic Ice Sheet. The main processes responsible for ice mass loss include: (1) ocean-driven melting of ice shelves by upwelling of warm water onto the continental shelf; and (2) atmospheric-driven surface melting of glaciers along the Antarctic coast. Understanding the relative influence of these processes on glacial stability is imperative to predicting sea-level rise. Employing a beryllium isotope-based reconstruction of ice-shelf history, we demonstrate that glaciers flowing into the Amundsen Sea Embayment underwent melting and retreat between 9 and 6 thousand years ago. Despite warm ocean water influence, this melting event was mainly forced by atmospheric circulation changes over continental West Antarctica, linked via a Rossby wave train to tropical Pacific Ocean warming. This millennial-scale glacial history may be used to validate contemporary ice-sheet models and improve sea-level projections.
Entropy and crystal-facet modulation of P2-type layered cathodes for long-lasting sodium-based batteries
Authors: Fu Fang , Liu Xiang , Fu Xiaoguang , Chen Hongwei , Huang Ling , Fan Jingjing , Le Jiabo , Wang Qiuxiang , Yang Weihua , Ren Yang , Amine Khalil , Sun Shi-Gang , Xu Gui-Liang
Published: May 2022

P2-type sodium manganese-rich layered oxides are promising cathode candidates for sodium-based batteries because of their appealing cost-effective and capacity features. However, the structural distortion and cationic rearrangement induced by irreversible phase transition and anionic redox reaction at high cell voltage (i.e., >4.0 V) cause sluggish Na-ion kinetics and severe capacity decay. To circumvent these issues, here, we report a strategy to develop P2-type layered cathodes via configurational entropy and ion-diffusion structural tuning. In situ synchrotron X-ray diffraction combined with electrochemical kinetic tests and microstructural characterizations reveal that the entropy-tuned Na0.62Mn0.67Ni0.23Cu0.05Mg0.07Ti0.01O2 (CuMgTi-571) cathode possesses more {010} active facet, improved structural and thermal stability and faster anionic redox kinetics compared to Na0.62Mn0.67Ni0.37O2. When tested in combination with a Na metal anode and a non-aqueous NaClO4-based electrolyte solution in coin cell configuration, the CuMgTi-571-based positive electrode enables an 87% capacity retention after 500 cycles at 120 mA g−1 and about 75% capacity retention after 2000 cycles at 1.2 A g−1.
Free charge photogeneration in a single component high photovoltaic efficiency organic semiconductor
Authors: Price Michael B. , Hume Paul A. , Ilina Aleksandra , Wagner Isabella , Tamming Ronnie R. , Thorn Karen E. , Jiao Wanting , Goldingay Alison , Conaghan Patrick J. , Lakhwani Girish , Davis Nathaniel J. L. K. , Wang Yifan , Xue Peiyao , Lu Heng , Chen Kai , Zhan Xiaowei , Hodgkiss Justin M.
Published: May 2022

Organic photovoltaics (OPVs) promise cheap and flexible solar energy. Whereas light generates free charges in silicon photovoltaics, excitons are normally formed in organic semiconductors due to their low dielectric constants, and require molecular heterojunctions to split into charges. Recent record efficiency OPVs utilise the small molecule, Y6, and its analogues, which – unlike previous organic semiconductors – have low band-gaps and high dielectric constants. We show that, in Y6 films, these factors lead to intrinsic free charge generation without a heterojunction. Intensity-dependent spectroscopy reveals that 60–90% of excitons form free charges at AM1.5 light intensity. Bimolecular recombination, and hole traps constrain single component Y6 photovoltaics to low efficiencies, but recombination is reduced by small quantities of donor. Quantum-chemical calculations reveal strong coupling between exciton and CT states, and an intermolecular polarisation pattern that drives exciton dissociation. Our results challenge how current OPVs operate, and renew the possibility of efficient single-component OPVs.