bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double‐blind, placebo‐controlled Phase 2 trial
Authors: Weiss Anne , Delavenne Emilie , Matias Carina , Lagler Heimo , Simon Daniel , Li Ping , Hansen Jon U. , dos Santos Teresa Pires , Jana Bimal , Priemel Petra , Bangert Christine , Bauer Martin , Eberl Sabine , Nussbaumer‐Pröll Alina , Anne Österreicher Zoe , Matzneller Peter , Quint Tamara , Weber Maria , Nielsen Hanne Mørck , Rades Thomas , Johansen Helle Krogh , Westh Henrik , Kim Wooseong , Mylonakis Eleftherios , Friis Christian , Guardabassi Luca , Pace John , Lundberg Carina Vingsbo , M'Zali Fatima , Butty Pascal , Sørensen Nikolaj , Nielsen Henrik Bjørn , Toft‐Kehler Rasmus , Guttman‐Yassky Emma , Stingl Georg , Zeitlinger Markus , Sommer Morten 
Published: May 2022

AbstractBackgroundIn patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed.Methods and findingsIn this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double‐blind and placebo‐controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild‐to‐severe AD (EudraCT:2016‐003501‐33). ATx201 has a narrow minimal inhibitory concentration distribution (.125–.5 μg/ml) consistent with its mode of action – targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin‐resistant S. aureus. In a Phase 2 trial in patients with mild‐to‐severe AD (N = 36), twice‐daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle.ConclusionThese results suggest that ATx201 could become a new treatment modality as a decolonizing agent.
HSP90 N‐terminal inhibitors target oncoprotein MORC2 for autophagic degradation and suppress MORC2‐driven breast cancer progression
Authors: Yang Fan , Sun Rui , Hou Zeng , Zhang Fang‐Lin , Xiao Yi , Yang Yun‐Song , Yang Shao‐Ying , Xie Yi‐Fan , Liu Ying‐Ying , Luo Cheng , Liu Guang‐Yu , Shao Zhi‐Min , Li Da‐Qiang 
Published: May 2022

AbstractAimsMORC family CW‐type zinc finger 2 (MORC2), a GHKL‐type ATPase, is aberrantly upregulated in multiple types of human tumors with profound effects on cancer aggressiveness, therapeutic resistance, and clinical outcome, thus making it an attractive drug target for anticancer therapy. However, the antagonists of MORC2 have not yet been documented.Methods and ResultsWe report that MORC2 is a relatively stable protein, and the N‐terminal homodimerization but not ATP binding and hydrolysis is crucial for its stability through immunoblotting analysis and Quantitative real‐time PCR. The N‐terminal but not C‐terminal inhibitors of heat shock protein 90 (HSP90) destabilize MORC2 in multiple cancer cell lines, and strikingly, this process is independent on HSP90. Mechanistical investigations revealed that HSP90 N‐terminal inhibitors disrupt MORC2 homodimer formation without affecting its ATPase activities, and promote its lysosomal degradation through the chaperone‐mediated autophagy pathway. Consequently, HSP90 inhibitor 17‐AAG effectively blocks the growth and metastatic potential of MORC2‐expressing breast cancer cells both in vitro and in vivo, and these noted effects are not due to HSP90 inhibition.ConclusionWe uncover a previously unknown role for HSP90 N‐terminal inhibitors in promoting MORC2 degradation in a HSP90‐indepentent manner and support the potential application of these inhibitors for treating MORC2‐overexpressing tumors, even those with low or absent HSP90 expression. These results also provide new clue for further design of novel small‐molecule inhibitors of MORC2 for anticancer therapeutic application.
Experimental investigation of super‐wideband 8‐port Multiple‐Input‐Multiple‐Output antenna with high isolation for future wireless applications including Internet of Things
Authors: Addepalli Tathababu , Sharma Manish , Nella Anveshkumar , Ambalgi Ambresh P. , Kapula Prabhakara Rao 
Published: May 2022

SummaryThe paper reports an experimental investigation of an 8 × 8 MIMO antenna fabricated on a commercially available FR4 substrate. A fractal printed monopole radiator is introduced as a good prospect for super‐wideband (2.85–20.0 GHz) multiple‐input‐multiple‐output (SWB‐MIMO) configuration. The MIMO antenna is printed on both the planes (Plane A and Plane B) where four antennas are printed on Plane A and remaining on Plane B which are fed asymmetric to achieve wider impedance bandwidth. An inverted‐L type strip is embedded in a rectangular elliptical slotted ground to match the impedance. Also, a circular ring is embedded on both planes with a novel stub connected to each antenna ground providing isolation of more than 30 dB. The diversity performance of the antenna is also investigated with measured envelope correlation coefficient (ECC) < 0.025, directive gain (DG) > 9.995 dB, total active reflection coefficient (TARC) < −40 dB, and channel capacity loss (CCL) < 0.30b/s/Hz in the entire operating band.
An energy aware cluster‐based routing and adaptive semi‐synchronized MAC for energy harvesting WSN
Authors: Movva Pavani , Kamarajugadda Kishore Kumar , Polipalli Trinatha Rao 
Published: May 2022

AbstractMedium access control (MAC) layer scheduling is an intelligent solution to protract the lifetime of energy harvesting wireless sensor network (WSN) which is challenging issue in recent times. Self‐adaptive MAC protocol was working upon reinforcement learning. However, this decentralized adaptive scheduling introduces collisions and degrades the overall network performance. To fix this problem, this paper proposes novel semi‐synchronized MAC approach for energy harvesting WSN. The major objective of this work is to improve energy efficiency of the network by minimizing energy consumption which is the major issue in WSN. Proposed WSN network is modeled with dual mobile sinks with circular moving path and static sensor nodes to monitor the environment. Our novel MAC approach is initiated with unequal cluster formation by correlation based unequal clustering scheme in which multi‐objective elephant herding optimization (CUC‐MEHO) algorithm is incorporated for cluster head (CH) selection. In clustered network, all sensor nodes follow semi‐synchronized adaptive active period MAC scheduling (S2A2MAC) protocol. In this work, S2A2MAC operates upon hidden Markov model (HMM) which controls the active time period of a node in an adaptive manner. Energy efficient hop‐by‐hop intra‐cluster routing is empowered by Bayes rule enabled perfect matching (BR‐PM) algorithm. Before route selection, all candidate nodes are regarded into perfect match, partially match, and no match nodes. Furthermore, emergency data is identified by CH based on flag value and transmitted without any time delay. For emergency data transmission, extremity aware routing (EAR) algorithm is presented and EAR algorithm is functioning on hopcount and distance criteria. Finally, proposed network is evaluated by extensive simulations in NS‐3.26. Simulation upshots show better performance in percentage of dead nodes, network lifetime, energy consumption, PDR, and delay.
Ortho‐F,F‐DPEphos: Synthesis and Coordination Chemistry in Rhodium and Gold Complexes, and Comparison with DPEphos
Authors: Race James J. , Webb Matthew J. , Morgan Boyd Timothy , Weller Andrew S. 
Published: May 2022

AbstractThe synthesis of a new ortho‐fluorine substituted diphosphine ligand based upon the DPEphos ligand is reported: o‐F,F‐DPEphos (DPEphos=bis(2‐diphenylphosphinophenyl)ether). The corresponding bimetallic gold complex Au2Cl2(o‐F,F‐DPEphos) and Schrock‐Osborn type Rh(I) complex [Rh(o‐F,F‐DPEphos)(NBD)][BArF4] have been synthesized (ArF=3,5‐(CF3)2‐C6H3). The solid‐state and solution phase NMR data are examined in comparison with the o‐H,H‐DPEphos equivalents, and demonstrate the influence of ortho‐fluorine substitution through the control of aurophilic and Rh⋅⋅⋅X interactions (X=H or F). Characterization of the organometallic products upon hydrogenation of the Schrock‐Osborn complexes in 1,2‐F2C6H4 revealed a Rh dimeric complex [Rh(H)(fac‐κ3‐P,O,P‐μ‐CH‐DPEphos)]2[BArF4]2 with a bridging C−H agostic interaction for the parent DPEphos. The substituted variant formed a Rh(III) monomer [Rh(mer‐κ3‐P,O,P‐o‐F,F‐DPEphos)H2][BArF4], highlighting the structural consequences of ortho‐fluorine substitution.
A width‐based approach to estimating historical changes in coarse sediment fluxes at river reach and network scales
Authors: Brenna Andrea , Bizzi Simone , Surian Nicola 
Published: May 2022

AbstractKnowledge about historical changes in sediment fluxes in most coarse‐bedded rivers worldwide is extremely limited. In consideration of this deficiency, we developed a width‐based approach to estimating multi‐decade changes in coarse sediment fluxes occurring at reaches of the Po River and 21 of its tributaries in northern Italy. The estimation was based on temporal variations in the reach‐averaged width of the river's active channel, and such width was expressed through a dimensionless index of coarse bed material load (Iq). The index was determined in two periods: 1954–1998 and 1998–2020. Statistically significant relationships were found between temporal variations in Iq occurring in reaches of the Po River and at key locations of each specific reach (i.e., upstream reaches and tributaries). Such evidence of coherent changes in sediment transfer through space and time led us to conclude that Iq variations can be regarded as a reliable proxy for historical changes in sediment transport in a river reach. The application of the approach to the investigation of the Po River catchment provided new insights into the historical changes characterizing coarse sediment fluxes along the river and its major tributaries. From 1954 to 1998, an average decrease in coarse sediment fluxes of about −20% and −30% occurred along the river and the terminal sectors of its tributaries, respectively. The estimations showed that coarse sediment fluxes exhibited a slightly lower decrease in the last two decades, with sediment flux recovery occurring only in some tributaries. The results suggest that a profound change in sediment dynamics and fluxes has occurred, and is likely still ongoing, in the Po River system, despite the decrease in human disturbances (e.g., in‐channel sediment mining) in more recent times.
Morpho‐sedimentary evolution of a microtidal meandering channel driven by 130 years of natural and anthropogenic modifications of the Venice Lagoon (Italy)
Authors: Finotello Alvise , Capperucci Ruggero M. , Bartholomä Alexander , D'Alpaos Andrea , Ghinassi Massimiliano 
Published: May 2022

AbstractTidal channels form the pathways for tidal currents to propagate and distribute clastic sediments and nutrients, thus providing a primary control on tidal‐landscape ecomorphodynamics. Most tidal channels in both estuarine and lagoonal environments have a tendency to meander, yet very few studies exist that investigate the full spectrum of processes controlling tidal meander morpho‐sedimentary evolution. The Venice Lagoon (Italy) offers a unique opportunity to shed light on this topic, because a long record of morphological and sedimentary data is available, which allows one to relate tidal channel evolution to the hydrodynamic and morphological changes undergone by the lagoon. In particular, during the last 130 years, feedback between rising relative sea levels and anthropogenic interventions has caused severe modifications of the Lagoon hydro‐ and morphodynamics. Here we investigate how these modifications fed back into the morpho‐sedimentary evolution of a meandering tidal channel located in the northern lagoon. Combining extensive datasets of aerial photographs, topographic and bathymetric surveys, geophysical investigations, sedimentary core analysis, and numerical modelling, we show that enhanced local tidal ranges and water discharges determined adjustments of channel cross‐sectional geometries proportional to increasing tidal prisms, while changes in local tidal asymmetries caused modifications of the local sediment transport regime, resulting in the development of bar–pool patterns according to the dominant tidal phase. Such bar–pool patterns eventually determined channel migration through a bar‐push mechanism controlled by a fluvial‐like, quasi‐linear relationship between local channel curvature and lateral migration rates. Critical differences in sediment transport regime are, however, highlighted between fluvial and tidal meanders the latter being potentially characterized by high concentrations of suspended sediment during periods of slack waters when wind‐driven sediment transport processes are not negligible. This could hamper the formation of high‐relief bedforms, with profound implications for the sedimentology of tidal point‐bar deposits.
NAFLD improves risk prediction of type 2 diabetes: with effect modification by sex and menopausal status
Authors: Kim Yejin , Chang Yoosoo , Ryu Seungho , Wild Sarah H. , Byrne Christopher D. 
Published: May 2022

Abstract

Background and Aims
The effects of sex and menopausal status on the association between NAFLD and incident type 2 diabetes (T2D) remain unclear. We investigated the effect modification by sex and menopause in the association between NAFLD and T2D; also, the added predictive ability of NAFLD for the risk of T2D was assessed.

Approach and Results
This cohort study comprised 245,054 adults without diabetes (109,810 premenopausal women; 4958 postmenopausal women; 130,286 men). Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident T2D according to NAFLD status. The incremental predictive role of NAFLD for incident T2D was assessed using the area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. A total of 8381 participants developed T2D (crude incidence rate/103 person‐years: 2.9 premenopausal women; 12.2 postmenopausal women; 9.3 men) during median follow‐up of 5.3 years. NAFLD was positively associated with incident T2D in all groups. After adjustment for potential confounders, the multivariable‐adjusted HRs (95% CIs) for incident T2D comparing NAFLD to no NAFLD were 4.63 (4.17–5.14), 2.65 (2.02–3.48), and 2.16 (2.04–2.29) in premenopausal women, postmenopausal women, and men, respectively. The risks of T2D increased with NAFLD severity as assessed by serum fibrosis markers, and the highest relative excess risks were observed in premenopausal women. The addition of NAFLD to conventional risk factors improved risk prediction for incident T2D in both sexes, with a greater improvement in women than men.

Conclusions
NAFLD, including more severe NAFLD, is a stronger risk factor for incident T2D in premenopausal women than in postmenopausal women or men; protection against T2D is lost in premenopausal women with NAFLD.
The role of blood urea nitrogen to serum albumin ratio in the prediction of severity and 30‐day mortality in patients with COVID‐19
Authors: Alirezaei Toktam , Hooshmand Saeede , Irilouzadian Rana , Hajimoradi Behzad , Montazeri Sadra , Shayegh Arash 
Published: May 2022

AbstractBackgroundConsidering the role of higher blood urea nitrogen and lower serum albumin (SA) levels in deceased coronavirus disease 2019 (COVID‐19) patients, an increased blood urea nitrogen to SA (B/A) ratio may help to determine those at higher risk of critical illness. This study aimed to evaluate the correlation of the B/A ratio with severity and 30‐day mortality in COVID‐19 patients.MethodsA total of 433 adult patients with COVID‐19 were enrolled. The laboratory markers were measured on admission. Disease severity was categorized into mild disease, severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and septic shock. The mortality was followed for 30 days after admission. χ2 test, Fisher's exact test, and Mann–Whitney U test were performed, as appropriate. Also, logistic regression and the receiver operating characteristic (ROC) curve for the B/A ratio are included.ResultsThirty‐day mortality rate was 27.25%. The frequency of mild, severe pneumonia, ARDS, sepsis, and septic shock was 30.72%, 36.95%, 24.02%, 6.00%, and 2.31%, respectively. B/A ratio and SA levels were statistically different between alive and deceased patients. The mean B/A ratio was different among classified disease severities, except for mild disease. Logistic regression revealed the B/A ratio as an independent risk factor for sepsis after adjusting for age and sex. ROC analysis showed B/A ratio had an area under the curve (AUC) of 0.733 for mortality at the cutpoint of 4.944. AUC for sepsis was 0.617 which was greater than other disease severities.ConclusionThe results showed that B/A ratio and SA levels are associated with mortality of COVID‐19 patients. A higher B/A ratio is, additionally, associated with COVID‐19 severity, except in mild cases and it can act as an independent risk factor in sepsis. However, a greater B/A ratio is not a significant predictor of COVID‐19 severity, but it can predict mortality. Therefore, we suggest this marker for clinical assessment of patients with severe COVID‐19.
The effects of prenatal smoke exposure on language development ‐ a systematic review
Authors: Peixinho Jessica , Toseeb Umar , Mountford Hayley S. , Bermudez Isabel , Newbury Dianne F. 
Published: May 2022

AbstractThe negative health effects of cigarette smoking during pregnancy (SDP) on the foetus are well known. Despite previous reports of poor cognitive performance in offspring exposed to SDP, few studies specifically consider language outcomes according to maternal smoking. In this study, we systematically review the literature to assess the relationships between SDP and child language. Of the 14 studies reviewed, 13 (93%) reported significant associations between maternal smoking or exposure and language outcomes. Despite this consistent association, only 8 of the 13 studies reporting associations (62%) concluded direct relationships between exposure and outcome. The remaining studies suggested that the relationship between smoking and language could be explained by factors such as maternal IQ, socioeconomic status (SES) and parental age. Future studies should apply careful study designs allowing for confounding factors across child, parental, environmental and genetic influences. Our review suggests that smoking cessation is likely to positively affect child language outcomes.Highlights
Does maternal smoking during or exposure to smoking during pregnancy affect the language outcomes in exposed offspring?
A systematic review of the literature highlighted consistent negative effects of smoking or smoke exposure during pregnancy on language outcomes.
Exposure to SDP is associated with language. Mothers must be educated regarding the effects of tobacco smoking on language outcomes.
Such a tease! Production and uses of teaser rams, bucks, boars and bulls
Authors: Crilly JP , Wood Max , Reilly Beth 
Published: May 2022

Background: Male livestock rendered sterile through vasectomy or epididymectomy, but still hormonally and behaviourally sexually active, have many uses. In small ruminants they can be used to advance the breeding season and puberty, synchronise and detect oestrus and improve conception rates to artificial insemination. In pigs, they can be used to hasten first oestrus in gilts and detect oestrus in sows. In cattle, they can be used to aid heat detection for artificial insemination.Aim of the article: This article outlines the surgical techniques used to produce such ‘teaser’ animals and discusses how they can be best used, as well as the alternatives to their use.
Experimental study on novel biodegradable Zn–Fe–Si alloys
Authors: Zeng Yuxin , Guan Zeyi , Linsley Chase S. , Pan Shuaihang , Liu Jingke , Wu Benjamin M. , Li Xiaochun 
Published: May 2022

AbstractBioabsorbable metals are increasingly attracting attention for their potential use as materials for degradable implant devices. Zinc (Zn) alloys have shown great promises due to their good biocompatibility and favorable degradation rate. However, it has been difficult to maintain an appropriate balance among strength, ductility, biocompatibility, and corrosion rate for Zn alloys historically. In this study, the microstructure, chemical composition, mechanical properties, biocompatibility, and corrosion rate of a new ternary zinc−iron–silicon (Zn–Fe–Si) alloy system was studied as a novel material for potential biodegradable implant applications. The results demonstrated that the in situ formed Fe–Si intermetallic phases enhanced the mechanical strength of the material while maintaining a favorable ductility. With Fe–Si reinforcements, the microhardness of the Zn alloys was enhanced by up to 43%. The tensile strength was increased by up to 76% while elongation to failure remained above 30%. Indirect cytotoxicity testing showed the Zn‐Fe‐Si system had good biocompatibility. Immersion testing revealed the corrosion rate of Zn–Fe–Si system was not statistically different from pure Zn. To understand the underlying phase formation mechanism, the reaction process in this ternary system during the processing was also studied via phase evolution and Gibbs free energy analysis. The results suggest the Zn–Fe–Si ternary system is a promising new material for bioabsorbable metallic medical devices.
Pregnenolone derivatives as potential anti‐lung cancer agents: A combined in silico and in vitro approach
Authors: Sethi Arun , Yadav Priyanka , Singh Ranvijay Pratap , Kumar Saurabh , Parveen Shama , Singh Asmita , Yadav Astha , Banerjee Monisha 
Published: May 2022

AbstractSynthesis of C‐3 and C‐20 pregnenolone derivatives using Steglich and Heck reaction has been reported. The structures of compounds were established by 1H, 13C NMR, NOESY, FT‐IR, and ESI‐MS. The anticancer activity against lung cancer proficiency assessment was performed using the prediction of activity spectra for substances (PASS) technique and the results were compared with the FDA‐approved lung cancer drug dacomitinib. Molecular docking studies were carried out to investigate the inhibitory action of steroidal derivatives against the lung cancer cell protein (2ITO). The result of the docking exhibited a significant inhibitory action against the lung cancer protein (2ITO) and the binding energy (ΔG) values of 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 against the protein 2ITO were found to be −10.1, −10.8, −9.2, −9.4, −10.1, −9.4, −11.0, −10.9, −9.7, and −9.5 Kcal/mol, respectively. In vitro lung cancer activity analyses of these compounds against lung cancer cell line (A549) showed that compounds 2 and 3 were more potent than other compounds. Results of in silico and in vitro analysis revealed that they showed good correlation. Drugs likeness and ADMET analysis of all derivatives have also been studied.