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Mobile instant messaging is widely used in governing circles today. This article considers the implications for political legitimacy, examining how far the technology encourages those in authority to act consistently with the obligations that come with their roles. It looks at several recent political scandals in which officeholders are alleged to have transgressed public norms with their use of instant messaging. It goes on to argue that the concerns raised are well grounded, as the affordances of the technology point to personalized, informal, and untransparent modes of rule. As the final section argues, that figures in public authority embrace the technology despite the scandals it can yield tells us something important about their political priorities, in particular their willingness to prize output over procedural legitimacy. [ABSTRACT FROM AUTHOR]

In helimagnetic metals, ac current-driven spin motions can generate emergent electric fields acting on conduction electrons, leading to emergent electromagnetic induction (EEMI). Recent experiments reveal the EEMI signal generally shows a strongly current-nonlinear response. In this study, we investigate the EEMI of Tb5Sb3, a short-period helimagnet. Using small angle neutron scattering we show that Tb5Sb3 hosts highly disordered helimagnetism with a distribution of spin-helix periodicity. The current-nonlinear dynamics of the disordered spin helix in Tb5Sb3 indeed shows up as the nonlinear electrical resistivity (real part of ac resistivity), and even more clearly as a nonlinear and huge EEMI (imaginary part of ac resistivity) response. The magnitude of the EEMI reaches as large as several tens of μH for Tb5Sb3 devices on the scale of several tens of μm, originating to noncollinear spin textures possibly even without long-range helimagnetic order. Ac current-driven spin motions in helimagnetic metals can generate emergent electric fields acting on conduction electrons, leading to emergent electromagnetic induction (EEMI). In this study, we revealed that a short-period helimagnet Tb5Sb3 may have disordered spin helix structure and provides large EEMI. [ABSTRACT FROM AUTHOR]

That democratic authorities are systematically focused on short-term considerations is a charge often made. This 'democratic myopia' thesis typically becomes the basis for advocating the empowerment of technocratic institutions, for example in economic policy. Much less examined is what one may call the technocratic myopia thesis – the possibility that technocratic institutions have their own distinctive drivers of short-termism. This article presents the case, with reference to the legitimacy forms, epistemologies and organisational structures in which technocratic authority is grounded. The suggestion is that not only may technocrats fall short of the claims to long-sightedness made of them, but that this is directly bound up in some of the core features of the technocratic method. The article goes on to discuss the implications for how contemporary societies govern the future in key domains of public policy. [ABSTRACT FROM AUTHOR]

This article contains a personal reflection of experiences in terrorism research over the past few decades. It begins by discussing early academic struggles to recognize the legitimacy of terrorism research, especially in the field of criminal justice. This is followed by a selective description of events where the author correctly predicted events as well as those where he was blindsided by surprises. It closes with an appeal to both the academy and the American public to move beyond ideology and populist understandings of terrorism to grapple with the multiple forms and complexities of terrorist violence. [ABSTRACT FROM AUTHOR]

International wild Atlantic salmon management priorities have moved from exploitation to conservation since the 1990s, recognizing the need to protect diversity and abundance at individual river levels amid widespread declines. Here we review international salmon-stock assessments and describe a simple, transferable catch-advice framework, established for management of fisheries that conforms to international obligations. The risk assessment approach, applied at the river scale, jointly incorporates uncertainty in estimated and forecasted returning salmon numbers with the level of uncertainty around spawning requirements (Conservation Limits). Outputs include quantification of risk of stocks not attaining conservation limits (CL) and surpluses above CL on stocks able to support sustainable exploitation via total allowable catches (TAC), with monitoring by rod catch or fish counter. Since management implementation and cessation of at-sea mixed-stock fisheries, there has been a deterioration in the performance of many individual stocks, without any sustained increase in fisheries open to harvest. Given declines in mid-latitude Atlantic salmon populations over 30 years, the novel framework presented provides an approach to protect stocks failing to meet spawning thresholds while supporting sustainable exploitation of those achieving them. On-going management policy of adopting scientific advice and allowing exploitation only on stocks exceeding CLs is central to the objective of protecting salmon stocks. [ABSTRACT FROM AUTHOR]

This study investigated the short-term responses of step characteristics in sprinters and team-sports players under different bend conditions. Eight participants from each group completed 80 m sprints in four conditions: banked and flat, in lanes two and four (L2B, L4B, L2F, L4F). Groups showed similar changes in step velocity (SV) across conditions and limbs. However, sprinters produced significantly shorter ground contact times (GCT) than team sports players in L2B and L4B for both left (0.123 s vs 0.145 s and 0.123 s vs 0.140 s) and right steps (0.115 s vs 0.136 s and 0.120 s vs 0.141 s) (p > 0.001–0.029; ES = 1.15–1.37). Across both groups, SV was generally lower in flat conditions compared to banked (Left: 7.21 m/s vs 6.82 m/s and Right: 7.31 m/s vs 7.09 m/s in lane two), occurring due to reduced step length (SL) rather than step frequency (SF), suggesting that banking improves SV via increased SL. Sprinters produced significantly shorter GCT in banked conditions that led to non-significant increases in SF and SV, highlighting the importance of bend sprinting specific conditioning and training environments representative of indoor competition for sprint athletes. [ABSTRACT FROM AUTHOR]

Using natural bond orbital theory, aromatic stabilization energies (NBO‐ASEs) were calculated for neutral and cationic monoheterocyclic three‐membered rings C2H2X(R)n (X = group 14–17 elements of rows 3–5; R = F, H or SiH3; and n = 0–2). Generally, there was a decrease in the (anti)aromatic nature of the molecule moving down the group as either the stabilizing orbital overlap (aromaticity) or destabilizing orbital interactions (antiaromaticity) were reduced due to larger atoms inducing longer bonds. (Anti)aromatic trends were supported with dissected nucleus independent chemical shift NICS(0)π,zz values (R2 = 0.94) and also by comparison of NBO‐ASEs to literature values for a selection of larger systems including benzene, cyclobutadiene, and the cyclopentadienyl anion. Comparisons are made to other studies that have used a range of approaches to study (anti)aromaticity in some of these molecules, and it was found that non‐dissected NICS values and homodesmotic equations often gave significantly overestimated if not misleading results. [ABSTRACT FROM AUTHOR]

Observation of the [M + H]+ ion in electrospray ionisation mass spectrometry (ESI‐MS) for either product identification or further unimolecular reactivity studies is not always guaranteed. When a suitable donor is β to a good leaving group such as protonated alcohols, neighbouring group participation (NGP) is one process that can lead to facile in‐source decomposition leading to three‐membered ring product ions. In this study, lone pair rich heteroatoms are explored computationally as donors for the intramolecular displacement of either water or ammonia in protonated 2‐heteroethanols and ethanamines, respectively. Density functional theory (DFT) calculations showed that for the halogens (Cl, Br and I) both the loss of water and ammonia are overall endothermic processes with modest barriers for the 2‐haloethanol fragmentation by NGP. The chalcogens (S, Se and Te) displayed a significant shift with the loss of water becoming exothermic and the enthalpic barrier approximately zero in most cases leading to little [M + H]+ ion observation. The loss of ammonia remained endothermic for both the chalcogens (S, Se and Te) and pnictogens (P, As and Sb), but the 2‐pnictoethanol fragmentation showed mixed results as two pathways were accessible due to the increased s character of the pnictogen lone pair. Examination of the donor–acceptor interactions by natural bond orbital (NBO) theory reflected an increase in the heteroatom lone pair participation at the transition state, but that stabilisation due to the polarisable CX bond dominated and should not be discounted in processes believed to proceed by nonvertical neighbouring group participation. [ABSTRACT FROM AUTHOR]

Four cutaneous lesions were described as red or erythematous papules or nodules, resembling the most typical appearance of cutaneous metastases for renal cell carcinoma.[2] One lesion was described as an erythematous plaque with central dark scale. Metastatic disease is present in up to 33% of newly diagnosed renal cell carcinomas (RCC).[1] The most common sites of spread are lung, bone, abdomen, and brain, but skin metastases may be present in up to 8% of cases.[[1]] Cutaneous metastatic lesions may have varying appearances but typically present as solitary black, brown, or violaceous papules, nodules, or plaques that grow rapidly.[2] Since metastatic lesions may be the first presentation of underlying malignancy and prompt recognition of metastatic disease could expedite treatment, we sought to characterize the most frequent cutaneous and subcutaneous metastatic destinations of renal cell carcinoma.[3] Upon Wake Forest School of Medicine Institutional Review Board approval, we performed a retrospective chart review of patients with RCC metastatic to the skin. Five lesions were described as deeper palpable nodules with or without superficial discoloration, suggesting lesions to be primarily located in the subcutaneous tissue. [Extracted from the article]

Co–Zn–Mn chiral cubic magnets display versatile magnetic skyrmion phases, including equilibrium phases stable far above and far below room temperature, and the facile creation of robust far‐from‐equilibrium skyrmion states. In this system, compositional disorder and magnetic frustration are key ingredients that have profound effects on the chiral magnetism. Reported here are studies of the magnetism in Co6.75Zn6.75Mn6.5 by magnetometry, small‐angle neutron scattering (SANS), magnetic diffuse neutron scattering and Lorentz transmission electron microscopy (LTEM). While features in magnetometry and LTEM often give standard indications for skyrmion formation, they are not readily observed from the measurements on this system. Instead, skyrmion lattice correlations are only revealed by SANS, and they are found to form an orientationally disordered structure in a minority fraction of the sample. The majority fraction of the sample always displays orientationally disordered helical spin correlations, which undergo further disordering along the radial direction on cooling below the critical temperature (Tc ≃ 102 K). The near‐complete suppression of the skyrmion phase, and the process of disordering on cooling, are attributed to competing magnetic interactions that dominate over the ferromagnetic interaction expected to favour chiral magnetism in this system. These competing interactions start to develop above Tc and become further enhanced towards low temperatures. The present observations of co‐existing and disordered magnetic correlations over multiple length scales are not unique to Co6.75Zn6.75Mn6.5 but are seemingly common to the family of Co–Zn–Mn compounds with finite Mn, and their accurate description presents a challenge for theoretical modelling. In addition, this study highlights a need for neutron instrumentation capable of the comprehensive measurement of magnetic correlations over expanded ranges of momentum transfer in such multiple‐length‐scale magnets. [ABSTRACT FROM AUTHOR]

The synthesis and structural characterisation of an icosanuclear silver(I) cluster complex is reported here. The complex includes twenty silver(I) ions supported by eighteen bis(thiosemicarbazonato) ligands. The cluster of silver(I) ions involves several close Ag⋯Ag contacts suggesting some degree of argentophilic interactions and the bis(thiosemicarbazonato) ligands are present in three different conformations highlighting the ability of thiosemicarbazone ligands to coordinate to metal ions in different modes. A complex that consists of twenty silver(I) ions supported by eighteen bis(thiosemicarbazonato) ligands is reported here. The cluster of silver(I) ions involves several close Ag⋯Ag contacts suggestive of argentophilic interactions and the bis(thiosemicarbazonato) ligands are present in three different conformations. [ABSTRACT FROM AUTHOR]

This piece outlines the concept of emergency politics as it may be applied to EU politics, distinguishing it from more familiar terms such as crisis management. We define emergency politics as a mode of politics in which actions departing from convention are rationalised as necessary responses to exceptional and urgent threats. Arguably, the many crises affecting the EU in the recent past have made this mode increasingly salient. To capture its various expressions, the article presents a new typology of the forms that emergency politics can take in this setting, identifying four in particular: supranational, multilateral, unilateral and domestic. It connects these to the events of the last decade, spanning eurozone economics, migration, and Covid-19. We conclude by considering the variable consequences of these different types of emergency politics, in particular for the EU's normative and sociological legitimacy. [ABSTRACT FROM AUTHOR]

The making of modern authority centred on efforts to formalise and de-personalise power, and transnational orders such as the European Union have often been viewed as an extension of that project. As this article argues, recent developments tell a different story. More than a decade of crisis politics has seen institutions subordinated to and reshaped by individuals and the networks they form. Locating these tendencies in a wider historical context, the article argues that greater attention to informality in transnational governance needs to be paired with greater recognition of the normative questions it raises. Just as a separation between rulers and the offices of rule was central to the making of modern legal and political structures, the weakening of that separation creates legitimacy problems for contemporary authorities both national and supranational. Rather than acclaimed as flexible problem-solving, the step back from institutions should be viewed as a challenge to accountable rule. [ABSTRACT FROM AUTHOR]

The organoselenium compound ebselen has recently been investigated as a treatment for COVID-19; however, efforts to model ebselen in silico have been hampered by the lack of an efficient and accurate method to assess its binding to biological macromolecules. We present here a Generalized Amber Force Field modification which incorporates classical parameters for the selenium atom in ebselen, as well as a positively charged pseudoatom to simulate the σ-hole, a quantum mechanical phenomenon that dominates the chemistry of ebselen. Our approach is justified using an energy decomposition analysis of a number of density functional theory–optimized structures, which shows that the σ-hole interaction is primarily electrostatic in origin. Finally, our model is verified by conducting molecular dynamics simulations on a number of simple complexes, as well as the clinically relevant enzyme SOD1 (superoxide dismutase), which is known to bind to ebselen. [ABSTRACT FROM AUTHOR]

77Se‐NMR is used to characterise several chalcogen bonded complexes of derivatives of the organoselenium drug ebselen, exploring a range of electron demand. NMR titration experiments support the intuitive understanding that chalcogen bond donors bearing more electron withdrawing substituents give rise stronger chalcogen bonds. The chemical shift of the selenium nucleus is also shown to move upfield as it participates in a chalcogen bond. Solid‐state NMR is used to explore chalcogen bonding in co‐crystals. Due to the lack of molecular reorientation on the NMR timescale in the solid state, the shape of the chemical shift tensor can be determined using this technique. A range of co‐crystals are shown to have extremely large chemical shift anisotropy, which suggests a strongly anisotropic electron density distribution around the selenium atom. A single crystal NMR experiment was conducted using one of the co‐crystals, affording the absolute orientation of the chemical shift tensor within the crystal. This showed that the selenium nucleus is strongly shielded in the direction of the chalcogen bond (due to the approach of the lone pair of the Lewis base), and strongly deshielded in the perpendicular direction. The orientation of the deshielded axis is consistent with the presence of a second σ‐hole which is not participating in a chalcogen bond, showing the profound effect of electron density anisotropy on the chemical shift. [ABSTRACT FROM AUTHOR]

In an age of grand coalitions, and widespread dissatisfaction with them, it is clear that one of the major challenges for contemporary parties is to pursue power without sacrificing the principles by which they define themselves. This points to one of the most important yet neglected criteria by which to assess an electoral system: its capacity to sustain principled partisanship. This paper makes a case for the distinctiveness of this criterion and why it should receive more attention. Drawing on the comparative politics of electoral systems, it examines the kinds of institutional feature relevant to an evaluation in these terms, and what it might mean to make institutions more conducive to a politics of firm commitments. [ABSTRACT FROM AUTHOR]

Social media (SM) use has accelerated at an unprecedented pace and dermatology literature evaluating SM use is primarily centered on the quality and quantity of dermatologic content, with minimal research on how adolescent patients experience such content. We recruited 15 patients between the ages of 13–18 years from the Atrium Health Wake Forest Baptist Department of Dermatology to interview regarding their experience with dermatologic content on SM. Despite most participants' insightful comments on SM use and the relative lack of dermatologic content validation on SM, many participants adopted skin care advice from SM. Adolescents are particularly vulnerable to social influence and it is important dermatologists understand how pervasive skin‐related content is on these platforms. [ABSTRACT FROM AUTHOR]

The crystal structure of the pyridine‐substituted benzisoselenazolinone 2‐(pyridin‐3‐yl)‐2,3‐dihydro‐1,2‐benzoselenazol‐3‐one (C12H8N2OSe, 2), related to the antioxidant ebselen [systematic name: 2‐phenyl‐1,2‐benzoselenazol‐3(2H)‐one, 1], is characterized by strong intermolecular N...Se(—N) chalcogen bonding, where the N...Se distance of 2.3831 (6) Å is well within the sum of the van der Waals radii for N and Se (3.34 Å). This strong interaction results in significant lengthening of the internal N—Se distance, consistent with significant population of the Se—N σ* antibonding orbital. Much weaker intermolecular O...Se chalcogen bonding occurs between the amide‐like O atom in 2 and the less polarized C—Se bond in this structure. Charge density analysis of 2 using multipole refinement of high‐resolution data allowed the electrostatic surface potential for 2 to be mapped, and clearly reveals the σ‐hole at the extension of the Se—N bond as an area of positive electrostatic potential. Topological analysis of the electron‐density distribution in 2 was carried out within the Quantum Theory of Atoms in Molecules (QTAIM) framework and revealed bond paths and (3,−1) bond critical points (BCPs) for the N...Se—N moiety consistent with a closed‐shell interaction; however, the potential energy term is suggestive of electron sharing. Analysis of the electron localization function (ELF) for the strong N...Se and the weak O...Se chalcogen‐bonding interactions in the structure of 2 suggest significant electron sharing in the former interaction, and a largely electrostatic interaction in the latter. Conversion of 2 to its N‐methylated derivatives by reaction with methyl iodide [1‐methyl‐3‐(3‐oxo‐2,3‐dihydro‐1,2‐benzoselenazol‐2‐yl)pyridin‐1‐ium iodide, C13H11N2OSe+·I−] and methyl tosylate [1‐methyl‐3‐(3‐oxo‐2,3‐dihydro‐1,2‐benzoselenazol‐2‐yl)pyridin‐1‐ium toluenesulfonate trihydrate, C13H11N2OSe+·C7H7O3S−·3H2O] removes the possibility of N...Se chalcogen bonding and instead structures are obtained where the iodide and tosylate counter‐ions fulfill the role of chalcogen‐bond acceptors, with a strong I−...Se interaction in the iodide salt and a weaker p‐Tol‐SO3−...Se interaction in the tosylate salt. [ABSTRACT FROM AUTHOR]

A new nano bio-coordination polymer, bio-CP 2, from an endogenous metal ion (calcium(II)) and vitamin B3 (nicotinic acid, NA), was synthesized in water by ultrasonic irradiation. The structure of bio-CP 2 reversibly changed under wet conditions. Bio-CP 2, as a thermodynamically stable coordination polymer, was used for the chemical loading of curcumin (CCM) to improve its solubility. The MTT analysis showed improved cytotoxicity of CCM after loading on bio-CP 2. The flow cytometry analysis of AGS cells (a human gastric adenocarcinoma cell line) after treatment with CCM and bio-CP 2@CCM indicated cell apoptosis of 3.49% and 78.68%, respectively. These results confirm that bio-CP 2, as a non-toxic coordination polymer, can be used as a drug delivery system to improve the water solubility and anticancer performance of CCM. [ABSTRACT FROM AUTHOR]

Background: Lumbar drain (LD) trials are used to temporarily divert CSF in order to predict clinical improvement prior to definitive CSF diversion in patients with a diagnosis of normal pressure hydrocephalus. New technology has improved clinical detection of subtle pupillary changes that may occur during CSF diversion trials. The aim of this study was to determine whether pupillary light response as recorded by automated pupillometry could be used to predict response during lumbar drain trials.Methods: The authors prospectively gathered quantitative pupillometry data on admission and following each CSF diversion in a cohort of 30 consecutive patients with a presumptive diagnosis of normal pressure hydrocephalus admitted to a university hospital for elective LD trial between January 1, 2020 and March 30, 2021. The value of pupillometry in predicting success of lumbar drainage in alleviating symptoms was correlated to clinical improvement during lumbar drainage.Results: Of the 29 patients undergoing a 4-day LD trial, 16 (55.2%) demonstrated clinical improvement. Pre-drainage pupillometry values did not differ between patients who had clinical improvement or no clinical improvement. Constriction velocity improved compared to baseline in patients who had a successful lumbar drain trial (LD +). There was a non-significant trend towards improved constriction velocity and improved dilation velocity found in patients even after the first aliquot drainage.Discussion: Baseline pupillary function by automated pupillometry did not predict clinical improvement during lumbar drain trials. Improvement in constriction and dilation velocity may be useful to monitor at the outset, after the initial drainage, and at completion of lumbar drain trials. [ABSTRACT FROM AUTHOR]

The emergence of new infectious diseases and their high mortality rate reveals the need for more attention to this area and the synthesis of new compounds. In this work, two mixed ligand cadmium(II) coordination polymers of [Cd(Phac)2(Dabco)(H2O)]n (1) and [Cd(Phac)(4,4′-Bpy)(OAc)]n (2) (Phac = phenylacetate, Dabco = 1,4-diazabicyclo[2.2.2]octane, 4,4′-Bpy = 4,4′-bipyridine, OAc = acetate) have been synthesized by the solvothermal, sonochemical and mechanochemical methods. Single-crystal X-ray diffraction analysis, Fourier-transform infrared (FT-IR) spectroscopy, X-ray powder diffraction (XRPD), field emission scanning electron microscopy (FE-SEM) and thermal techniques (TG-DTG) were used to study these compounds. In both compounds, phenylacetate is obtained by in situ decarboxylation of phenylmalonic acid. The stability and in vitro antibacterial activity of the compounds were investigated. Metal–ligand bond strength, pillar size, ligand shielding effect, and the nature of network expansion bonds were influential factors in the stability. More stability and the consequent higher lipophilicity of particles were associated with improved antibacterial activity for 1. Nano-grains in the bulk structure of compounds were also identified as a determining factor in antibacterial activity. [ABSTRACT FROM AUTHOR]

Background Context: There has been a shift in the spine literature in reporting meaningful outcomes, including meaningful clinically important difference (MCID), after surgery. The evidence on the effect of tobacco smoking at the time of lumbar tubular microdecompression (LTMD) on meaningful outcomes is limited.Purpose: To compare differences in 1-year functional outcomes and rates of achieving MCID between current smokers and non-smokers who underwent LTMD for lumbar spinal stenosis (LSS).Study Design: A nested case control study to compare the difference in patient reported outcomes (PROs) between smokers and non-smokers 1-year after undergoing LTMD.Patient Sample: This study included patients that underwent single level LTMD by a single surgeon between January 2014 through August 2019.Outcome Measures: Preoperative and postoperative PROs were recorded using the questionnaires EQ-5D, Oswestry Disability Index (ODI), and the visual analog scale (VAS) for back pain and leg pain. The MCID was also used.Methods: Current tobacco smokers at the time of surgery were matched 1:2 to non-smokers by age (+/- 1year). Preoperative and postoperative functional scores were compared between the two groups using independent t-tests. Additionally, thresholds for achieving MCID were calculated for each individual functional score, and were compared using Fisher's exact test.Results: Of the 183 patients with 1-year follow-up who met inclusion criteria, 35 patients were identified as smokers and were matched to 70 non-smokers. No statistical differences were identified between age, BMI, or gender. Comparison of preoperative PROs showed no statistically significant differences between smokers and non-smokers (p>0.05 for all), while smokers had statistically lower EQ-5D (p<0.001) and higher ODI (p=0.05), VAS back (p=0.033), and VAS leg (p=0.03) score averages at a minimum of one year follow-up. Evaluation of meaningful outcomes demonstrated non-smokers had higher rates of achieving MCID on at least 1 threshold score as compared to smokers (98.5% vs. 91.1%; p=0.043).Conclusions: Current smokers at the time of surgery have inferior postoperative EQ-5D scores, increased pain and disability, and lower odds of achieving the MCID at 1-year after undergoing LTMD when compared to patients without any smoking history. [ABSTRACT FROM AUTHOR]

Background: Left ventricular free wall rupture (LVFWR) and interventricular septal rupture (VSR) are potentially catastrophic mechanical complications after acute myocardial infarction (AMI). When they occur together, “double myocardial rupture” (DMR), survival is unlikely. DMR is seen in only 0.3% of all AMIs. With or without surgical intervention, the odds are against the patient. Case presentation: A 57-year-old male self-referred to the emergency department of a remote hospital 5 days after first experiencing chest pain. Investigations in ED confirmed an inferior ST-segment elevation myocardial infarction (STEMI) complicated by DMR. Coronary angiography revealed a mid-course total occlusion of the right coronary artery (RCA). He was rapidly transferred to our regional cardiac surgical unit, arriving straight into the operating theatre, in cardiogenic shock. He was briefly conscious, before arresting prior to intubation and being massaged onto bypass. Not only did he survive the all-night operation, requiring a mitral valve replacement in the process, but he survived multiple postoperative complications to be eventually transferred on postoperative day 66, neurologically intact, to a peripheral unit to complete his rehabilitation. He was subsequently discharged home 88 days after the operation and was able to ambulate with a walking frame into his first postoperative follow-up clinic appointment. Conclusions: Our patient, against all odds, has survived DMR and multiple postoperative complications. We present the details of his case and the literature surrounding the condition. The patient’s mental fortitude and his supportive family played a significant role, along with excellent multidisciplinary team work, in assuring his survival. [ABSTRACT FROM AUTHOR]

Singlet fission (SF) is a potential avenue for augmenting the performance of silicon photovoltaics, but the scarcity of SF materials energy‐matched to silicon represents a barrier to the commercial realization of this technology. In this work, a molecular engineering approach is described to increase the energy of the S1 and T1 energy levels of diketopyrrolopyrrole derivatives such that the energy‐level requirements for exothermic SF and energy‐transfer to silicon are met. Time‐resolved photoluminescence studies show that the silicon‐matched materials are SF active in the solid state, forming a correlated triplet pair 1(TT) – a crucial intermediate in the SF process – as observed through Herzberg‐Teller emission from 1(TT) at both 77 K and room temperature. Transient electron paramagnetic resonance studies show that the correlated triplet pair does not readily separate into the unbound triplets, which is a requirement for energy harvesting by silicon. The fact that the triplet pair do not separate into free triplets is attributed to the intermolecular crystal packing within the thin films. Nevertheless, these results demonstrate a promising route for energy‐tuning silicon‐matched SF materials. [ABSTRACT FROM AUTHOR]

In this report, a microporous metal–organic framework of [Ca(TDC)(DMA)]n (1) and a two‐dimensional coordination polymer of [Ca(TDC)(DMF)2]n (2), (TDC2−=Thiophene‐2,5‐dicarboxylate, DMA=N, N'‐dimethylacetamide and DMF=N, N'‐dimethylformamide) based on Ca(II) were designed by the effect of solvent, and X‐ray analysis was performed for the single crystals of 1 and 2. Then, compound 1 was synthesized in three different methods and identified with a set of analyses. Compared to other adsorbents, MOFs are widely used in the field of adsorption and separation of various gases due to a series of distinctive features such as diverse and adjustable structures pores with different dimensions, high porosity and surface area with regular distribution of active sites. Therefore, the ability of 1 to uptake single gases (CH4, CO2, C2H2, H2, and N2) and separation of several binary mixtures of gases (CO2/CH4, CO2/N2, CO2/H2 and CO2/C2H2), were investigated using Grand Canonical Monte Carlo simulations. Volumetric and gravimetric adsorption isotherms in various operating conditions, the isosteric heat of adsorption (qst), the chemical potential for each thermodynamic state, and snapshots during the simulation process were reported in all cases. The results obtained from the adsorption simulation indicate that compound 1 has a high capacity for uptake of H2 (16 mmol g−1) and N2 (12.5 mmol g−1), CO2 (6.6 mmol g−1), C2H2 (5 mmol g−1) and CH4 (1.5 mmol g−1) gases at 1 bar. It also performs well in separating CO2 in binary mixtures, which can be attributed to the presence of open metal sites in nodes of 1 and their electrostatic tendency to interact with CO2 containing the higher quadrupole dipole moment compared to other components of the mixture. [ABSTRACT FROM AUTHOR]

Single‐crystal X‐ray diffraction studies for a variety of metal ion complexes of functionalised sarcophagines (sarcophagine=sar=3,6,10,13,16,19‐hexa‐azabicyclo[6.6.6]icosane) have further confirmed not only that the form of the metal ion/sar unit is unique for each metal, albeit with a sensitivity of the conformation to the associated counter anions, but also that for any given metal and ligand substituent, the dimensions (bond lengths and angles) of the complex and the substituent at the secondary nitrogen centres do not differ significantly from those of the isolated components. Despite this, where the substituent contains reactive sites, the reactivity differs markedly from that of their form in an uncoordinated substrate. Rationalisations are offered for these differences, in part through the use of Hirshfeld surface analysis of the intermolecular interactions. The kinetic inertness of the complexes means that the metal ions can be considered to act as regioselective protecting groups. [ABSTRACT FROM AUTHOR]

A new N2O2‐tetradentate Schiff base ligand entitled as N,N′‐((ethane‐1,2‐diybis [oxy])bis (ethan‐2,1‐diyl))bis(3‐(4‐methoxyphenyl)prop‐2‐en‐1‐imine was prepared by direct reaction between 3‐(4‐methoxyphenyl)‐2‐propenal and 1,8‐diamino‐3,6‐dioxaoctane. After characterization of the ligand, some novel cadmium coordination compounds formulated as CdLX2 (X: Cl−, Br−, I−, N3−, SCN−and NO3−) were synthesized and characterized by physical and spectral techniques. Typically crystal structure of cadmium nitrate coordination compound was determined suggesting crystallization in monoclinic system (with space group of I2/a) and a coordination geometry of square anti‐prism around the Cd (II) ion. Moreover, CdLBr2 and CdLI2 compounds were prepared in nanostructured dimensions by sonochemical method confirmed by SEM, EDX, and XRD techniques. In continuation, thermal behavior investigation of the compounds including thermal stabilities, thermal decomposition steps, and thermo‐kinetic parameters was performed based on Coats‐Redfern equations from room temperature to 900 °C. Furthermore, all the compounds were subjected to bioassay against two Gram‐positive bacteria of Staphylococcus aureus and Bacillus subtilis, two Gram‐negative bacteria of Pseudomonas aeruginosa and Escherichia coli, and two fungal strains of Aspergillus oryzae and Candida albicans. The results showed that all the synthesized compounds act well as antimicrobial agents. DNA cleavage power of the materials was also evaluated using extracted DNA from E. coli bacterium. The cytotoxic activities of some compounds were investigated against the prostate cancer cell lines (PC3) and human umbilical vein endothelial cells (HUVEC) (as normal cells) by MTT assay and nitric oxide level evaluation method as compared with cis‐platin confirming anti‐cancer effects of them. Finally, the antioxidant properties of the N2O2‐ligand and its cadmium coordination compounds were examined by DPPH and FRAP methods suggesting all the compounds have good antioxidant activity as compared with standard samples. [ABSTRACT FROM AUTHOR]

Background Endoscopic surveillance of Barrett's esophagus (BE) with Seattle protocol biopsies is time-consuming and inadequately performed in routine practice. There is no recommended procedural time for BE surveillance. We investigated the duration of surveillance procedures with adequate tissue sampling and effect on dysplasia detection rate (DDR). Methods We performed post hoc analysis from the standard arm of a crossover randomized controlled trial recruiting patients with BE (≥C2 and/or ≥M3) and no clearly visible dysplastic lesions. After inspection with white-light imaging, targeted biopsies of subtle lesions and Seattle protocol biopsies were performed. Procedure duration and biopsy number were stratified by BE length. The effect of endoscopy-related variables on DDR was assessed by multivariable logistic regression. Results Of 142 patients recruited, 15 (10.6 %) had high grade dysplasia/intramucosal cancer and 15 (10.6 %) had low grade dysplasia. The median procedural time was 16.5 minutes (interquartile range 14.0–19.0). Endoscopy duration increased by 0.9 minutes for each additional 1 cm of BE length. Seattle protocol biopsies had higher sensitivity for dysplasia than targeted biopsies (86.7 % vs. 60.0 %; P = 0.045). Longer procedural time was associated with increased likelihood of dysplasia detection on quadrantic biopsies (odds ratio [OR] 1.10, 95 %CI 1.00–1.20, P = 0.04), and for patients with BE > 6 cm also on targeted biopsies (OR 1.21, 95 %CI 1.04–1.40; P = 0.01). Conclusions In BE patients with no clearly visible dysplastic lesions, longer procedural time was associated with increased likelihood of dysplasia detection. Adequate time slots are required to perform good-quality surveillance and maximize dysplasia detection. [ABSTRACT FROM AUTHOR]

• A stable 3D Co(II)-based coordination polymer was synthesized and characterized. • The solvent stability test was conducted in various common organic solvents. • The cytotoxicity was evaluated by MTT assays against HEK-293 cell line. • This polymer showed significant antibacterial activity against the investigated strains. • This polymer recognized as a desirable antibacterial agent. The current work reports the facile synthesis and complete characterization of a stable 3D Co(II)-based coordination polymer, namely Co(HCOO) 2 (4,4′-bpy) (1), (4,4′-bpy=4,4′-bipyridine), prepared via two different synthetic methods including solvothermal reaction and reflux method. The Co-coordination polymer was fully characterized by 1H NMR, FT-IR, FE-SEM, TGA, ICP, BET, single-crystal X-ray crystallography, powder X-ray diffraction crystallography, and VSM analysis. The cell treatment with Co-coordination polymer was evaluated, and the cytotoxicity study was done by MTT assays against the HEK-293 cell line. Furthermore, the antibacterial properties of Co-coordination polymer nanoparticles were investigated. The Co-coordination polymer showed significant antibacterial properties against the selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. A stable 3D Co(II)-based coordination polymer, Co(HCOO) 2 (4,4′-bpy), was synthesized via two facile different synthetic methods, including solvothermal reaction and reflux method. It was fully characterized and the cytotoxicity was evaluated by MTT assays against HEK-293 cell line. The Co-coordination polymer showed significant antibacterial activity against the strains of Gram-negative and Gram-positive bacteria. The antibacterial properties of this polymer are due to a combination of physicochemical properties such as solubility, shape, size and specific surface area. [Display omitted] [ABSTRACT FROM AUTHOR]

Bromodomain and extraterminal (BET) proteins, a family of epigenetic regulators, have emerged as important oncology drug targets. BET proteins have not been targeted for molecular imaging of cancer. Here, we report the development of a novel molecule radiolabelled with positron emitting fluorine-18, [18F]BiPET-2, and its in vitro and preclinical evaluation in glioblastoma models. [ABSTRACT FROM AUTHOR]

With the aim of developing the concept of pretargeted click chemistry for the diagnosis of Alzheimer's disease two antibodies specific for amyloid-β were modified to incorporate trans-cyclooctene functional groups. Two bis(thiosemicarbazone) compounds with pendant 1,2,4,5-tetrazine functional groups were prepared and radiolabelled with positron emitting copper-64. The new copper-64 complexes rapidly react with the trans-cyclooctene functionalized antibodies in a bioorthogonal click reaction and cross the blood–brain barrier in mice. [ABSTRACT FROM AUTHOR]

Purpose: The interest in exploiting Auger emitters in cancer therapy stems from their high linear energy transfer (LET)-type radiation damage to DNA. However, the design of Auger-emitter labeled vehicles that target the Auger cascade specifically to the DNA of tumour cells is challenging. Here we suggest a possible approach to evaluate tumour-targeting Auger-labeled conjugates by assessing the impact of a radioprotector known to be effective in protecting from low LET radiation, but not high LET radiation. Given some similarity between the energy spectrum of Auger electrons and that of secondary electrons from soft X-rays, we report the results of radioprotection experiments with 25 kVp X-rays. Materials and methods: Clonogenic survival curves for cultured human keratinocytes were established for three different irradiation conditions: 137Cs γ-rays, 25 kVp X-rays and 320 kVp X-rays, and the effect of including a new radioprotector, denoted "2PH", was investigated. Results: The extent of radioprotection by 2PH was comparable for all radiation conditions, although RBE was higher (about 1.7) for soft X-rays. Conclusions: Radioprotectors like 2PH will help to evaluate Auger endoradiotherapy strategies, by determining the relative contributions of the high-LET effects (not protected), compared to other components, such as Auger electrons not effectively targeted to DNA. [ABSTRACT FROM AUTHOR]

Delays beyond recommended wait times, especially for specialist services, are associated with adverse health outcomes. The Alberta Surgical Initiative aims to improve the referral wait time—the time between a referral is received at the central intake to the time a specialist sees the patient. Using the discrete event simulation modelling approach, we evaluated and compared the impact of four referral distribution policies in a central intake system on three system performance measures (number of consultations, referral wait time and surgeon utilization). The model was co-designed with clinicians and clinic staff to represent the flow of patients through the system. We used data from the Facilitated Access to Surgical Treatment (FAST) centralized intake referral program for General Surgery to parameterize the model. Four distribution policies were evaluated – next-available-surgeon, sequential, "blackjack," and "kanban." A sequential distribution of referrals for surgical consultation among the surgeons resulted in the worst performance in terms of the number of consultations, referral wait time and surgeon utilization. The three other distribution policies are comparable in performance. The "next available surgeon" model provided the most efficient and robust model, with approximately 1,000 more consultations, 100 days shorter referral time and a 14% increase in surgeon utilization. Discrete event simulation (DES) modelling can be an effective tool to illustrate and communicate the impact of the referral distribution policy on system performance in terms of the number of consultations, referral wait time and surgeon utilization. [ABSTRACT FROM AUTHOR]

Intermetallic Pd‐doped (Fe,Ni)3P, which crystallizes in a non‐centrosymmetric tetragonal structure with S4 symmetry, has recently been discovered to host magnetic antiskyrmions, antivortex‐like topological spin textures. In this material, uniaxial magnetic anisotropy and dipolar interactions play a significant role, giving rise to finely branched magnetic domain patterns near the surface of bulk crystals, as revealed by a previous magnetic force microscopy (MFM) measurement. However, small‐angle neutron scattering (SANS) is a more suitable method for characterizing bulk properties and fractal structures on the mesoscopic length scale. In this study, using SANS and MFM, the magnetic domain structure in bulk single crystals of (Fe0.63Ni0.30Pd0.07)3P is quantitatively investigated. The SANS results demonstrate that the magnetic domain structure exhibits anisotropic fractal character on length scales down to the width of the magnetic domain walls. The fractal features are gradually lost in magnetic fields, and different field dependencies are observed at 300 and 2 K due to a temperature‐dependent anisotropy. This study quantifies the fractality of the highly anisotropic magnetic domain structures in an antiskyrmion material, and highlights the versatility of SANS for the study of fractal structures in magnetic systems. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma (MM) is an incurable cancer of the serosal lining that is often caused by exposure to asbestos. Therefore, novel agents for the prevention and treatment of this disease are urgently needed. Asbestos induces the release of pro-inflammatory cytokines such as IL-1β and IL-6, which play a role in MM development. IL-6 is a component of the JAK-STAT3 pathway that contributes to inflammation-associated tumorigenesis. Glycoprotein 130 (gp130), the signal transducer of this signaling axis, is an attractive drug target because of its role in promoting neoplasia via the activation of downstream STAT3 signaling. The anticancer drug, SC144, inhibits the interaction of gp130 with the IL-6 receptor (IL6R), effectively blunting signaling from this inflammatory axis. To test whether the inflammation-related release of IL-6 plays a role in the formation of MM, we evaluated the ability of SC144 to inhibit asbestos-induced carcinogenesis in a mouse model. The ability of sulindac and anakinra, an IL6R antagonist/positive control, to inhibit MM formation in this model was tested in parallel. Asbestos-exposed Nf2 +/− ;Cdkn2a +/− mice treated with SC144, sulindac or anakinra showed significantly prolonged survival compared to asbestos-exposed vehicle-treated mice. STAT3 activity was markedly decreased in MM specimens from SC144-treated mice. Furthermore, SC144 inhibited STAT3 activation by IL-6 in cultured normal mesothelial cells, and in vitro treatment of MM cells with SC144 markedly decreased the expression of STAT3 target genes. The emerging availability of newer, more potent SC144 analogs showing improved pharmacokinetic properties holds promise for future trials, benefitting individuals at high risk of this disease. [ABSTRACT FROM AUTHOR]

The structure of the title compound, 2C18H19ClN4O-HCl or (CNO)2-HCl (C36H39Cl3N8O2), at 100 K has tetragonal (I4/m) symmetry. The dihedral angle between the benzene rings of the fused ring system of the CNO molecule is 40.08 (6)° and the equivalent angle between the seven-membered ring and its pendant N-oxide ring is 31.14 (7)°. The structure contains a very strong, symmetrical O--H--O hydrogen bond [O--O = 2.434 (2) JA] between two equivalent R3N+ -- O_ moieties, which share a proton lying on a crystallographic twofold rotation axis. These units then form a (CNO)4-(HCl)2 ring by way of two equivalent N--H--Cl hydrogen bonds (Cl_ site symmetry m). These rings are catenated into infinite chains propagating along the c-axis direction by way of shape complementarity and directional C--H--N and C--H--tt interactions. [ABSTRACT FROM AUTHOR]

• Synthesis of five hydrazinylidene-benzothiazinedione derivatives. • Diverse supramolecular networks of noncovalent interactions. • Assessment of energetic properties of the supramolecular dimers using QTAIM/NCI plot methods. • Compound 9b emerged as the lead inhibitor with strong efficacy. • Molecular docking analysis revealed several key interactions within the active site of urease. The intricate role of noncovalent interactions in numerous fields including chemistry, biology, catalysis, material science, and medicinal chemistry provides a continuous impetus towards the discovery of new synthons that stabilize the supramolecular architectures. In this regard, the current work presents a series of five hydrazinylidene-benzothiazinedione derivatives encompassing a wide plethora of noncovalent interactions. Despite the configurational similarity of their hydrazinylidene-benzothiazinedione component, the five crystallographic packing arrangements of 7a – c and 9a,b are unique. The principal intermolecular interactions are C H⋯O hydrogen bonds and weak C H···π interactions (Malone Type III). Inversion dimers based on C H⋯Cl interactions form for 7b while C H⋯N and C H⋯S interactions in 9a were also observed. Furthermore, the energetic properties of the supramolecular dimers, centrosymmetric (antiparallel oriented) arrangements in 7a and 7b while parallel oriented arrangements in 9a and 9b have been examined using a combined QTAIM/NCI plot methods. The medicinal chemistry potential against urease enzyme revealed compound 9b as the lead inhibitor with strong efficacy (IC 50 = 0.92 ± 0.03 µM). In vitro results were complemented with molecular docking revelations where several key interactions were observed between the potent ligand and active site amino acids. ADMET profile also described compounds 7b and 9b as the best molecules with promising druglike profile. This manuscript presents the synthesis and analysis of noncovalent interactions in hydrazinylidene-benzothiazinediones supported by QTAIM/NCIplot method followed by biochemical and in silico assessment against urease enzyme. [Display omitted] [ABSTRACT FROM AUTHOR]

As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung, and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here, after demonstrating in vitro neutralization of SARS-CoV-2 by APN01, and after obtaining preliminary evidence of its tolerability and preventive efficacy in a mouse model, we pursued development of an aerosol formulation. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers has now been initiated (NCT05065645), with subsequent Phase II testing planned for individuals with SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU).Methods: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization.Results: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups.Conclusions: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.). [ABSTRACT FROM AUTHOR]

Three cadmium(II) coordination polymers, namely {[Cd(HLI)(NO3)2]·0.5MeOH}n (1), {[Cd(HLII)(NO3)2]·EtOH}n (2), and [Cd2(LII)2(NO3)2]n (3), have been self-assembled from Cd(NO3)2 and N,N′,O-pincer-type isonicotinoylhydrazone-based ditopic ligands (HLI = N′-(pyridin-2-ylmethylene)isonicotinohydrazide and HLII = N′-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide) and have been characterized experimentally and by DFT computations. In compounds 1 and 2, the corresponding ligand is coordinated to the metal center in the keto form and acted as a tetradentate chelating–bridging agent in which the nitrogen atom of the 4-pyridine ring is coordinated to the cadmium center of the neighboring unit, yielding 1D zig-zag coordination polymers. In compound 3, the ligand was singly-deprotonated and is coordinated in the enolic form with the nitrate ion further acted as a bridging agent, yielding a 2D network. It is revealed by the extended transition state natural orbital for chemical valence (ETS-NOCV) charge and energy decomposition scheme that typical hydrogen bonds O–H⋯O and N–H⋯O, which constitute the networks of 1 and 2, though dominated by a classic Coulomb term, are characterized by an equally important London dispersion constituent due to extra π⋯π and C–H⋯X contacts (X = O, H–C, H–N). The architecture of 3 is due to ionic and dative-covalent Cd–X (X = N, O) bonds as well as London dispersion-driven homopolar dihydrogen C–H⋯H–C and C–H⋯O interactions. NOCV-based representation allowed us to determine that hydrogen bonds O–H⋯O are twice weaker than the corresponding N–H⋯O in the networks of 1 and 2. [ABSTRACT FROM AUTHOR]

As a platinum-containing anticancer drug, cisplatin is the keystone for treating many malignancies. Nephrotoxicity is the main dose-limiting toxicity, and several hydration therapies and supplementary strategies are utilized to reduce cisplatin-induced kidney damage, so the discovery and development of effective and safe antitumor drugs are still on the path of human health. Herein, a new four-coordinated Pt complex [Pt(TSC)Cl] using N(4)-phenyl-2-formylpyridine thiosemicarbazone (HTSC) was synthesized and characterized by single-crystal X-ray diffraction, 1HNMR, FT-IR, LC/MS and CHN elemental analysis. The Pt(TSC)Cl complex revealed antiproliferative activity against A549, MCF-7 and Caco-2 cell lines with a low micromolar IC50 (200–1.75 µM). Specifically, the Pt(TSC)Cl complex displayed more selectivity in Caco-2 cells (IC50 = 2.3 µM) than cisplatin (IC50 = 107 µM) after 48 h of treatment. Moreover, compared with cisplatin, a known nephrotoxic drug, the Pt(TSC)Cl complex exhibited lower nephrotoxicity against Hek293 normal cells. We also found that the Pt(TSC)Cl complex can effectively prevent cancer cell propagation in sub-G1 and S phases and induce apoptosis (more than 90%). Real time PCR and western analysis demonstrated that the expression pattern of apoptotic genes and proteins is according to the intrinsic apoptosis pathway through the Bax/Bcl-2-Casp9-Casp3/Casp7 axis. Collectively, our findings indicated that the Pt(TSC)Cl complex triggers apoptosis in Caco-2 cell lines, while low nephrotoxicity was shown and may be considered a useful anticancer drug candidate for colorectal cancers for further optimization and growth. [ABSTRACT FROM AUTHOR]

Objective: Normal pressure hydrocephalus (NPH) is characterized by pathologically enlarged ventricles without elevated cerebrospinal fluid (CSF) pressure along with a triad of clinical symptoms including gait disturbances, urinary incontinence, and cognitive impairment. NPH is evaluated with lumbar drain trials (LDTs) where CSF is removed over several days to determine if patients would benefit from ventricular shunting. Candidate selection and success for these surgeries remains challenging because other diseases such as Alzheimer's disease (AD) share common features with NPH in cognitive impairment and enlarged ventricles. Prior research has found that 20%-40% of presumed NPH cases have AD pathology as determined by brain biopsy or autopsy. CSF biomarkers of AD can be altered in NPH and are not always conclusive, complicating the interpretation of results when formulating diagnoses and prognoses. Studies to refine the analyses of AD CSF biomarkers in NPH are needed. We aimed to examine the frequency of CSF biomarker results among patients presenting for NPH evaluations with LDTs. Participants and Methods: 62 patients presented for LDTs upon physician recommendations. CSF specimens were sent to Mayo Clinic Laboratories for Alzheimer Disease Evaluation (ADEVL) that utilizes Elecsys (Lenexa, KS) CSF electrochemiluminescence immunoassays (Roche Diagnostics, Basel, Switzerland) to measure levels of amyloid-beta 42 (Aβ42), total tau (t-tau), and phosphorylatedtau (p-tau), and p-tau:Aβ42 ratio. Results were classified based on interpretation through the Amyloid/Tau/Neurodegeneration (ATN) framework1: 1) AD - biomarker profile consistent with AD pathologic change, 2) non-AD profile - biomarker levels normal or inconsistent with AD pathologic change, or 3) indeterminate - biomarkers were incongruous with only one or two abnormal levels of Aβ42, t-tau, p-tau, or ptau: Aβ42. Indeterminate cases may represent altered protein levels due to CSF dynamics or AD-related pathologic change. In reviewing recent research on CSF dynamics and AD biomarkers in NPH2 a p-tau threshold of 15 pg/mL was derived and implemented such that cases with Aß42 <=1026 pg/mL and p-tau <15 pg/mL were designated as suspected non-AD, and those with Aß42 <=1026 pg/mL and p-tau >15 pg/mL were designated suspected AD. Results: Of the 62 LDT cases, 12 (19.35%) were classified as AD, 31 (50%) were indeterminate and 22 (35.48%) were non-AD. Of the 31 indeterminate cases, 21 (33.87% of the overall sample) were suspected non-AD and 7 (11.29% of the full sample) were categorized as suspected AD. Conclusions: Our findings show that 20%-30% of patients presenting for LDT showed evidence for AD-type pathologic change, consistent with prior reports of AD pathology in cases of possible NPH. Half of all LDT cases had indeterminate AD CSF biomarker results, the interpretations of which were confounded by the potential alterations of CSF biomarkers levels due to NPH independent of AD. Our findings emphasize the need to establish better approaches to interpreting CSF AD biomarkers in evaluating NPH. Future research should examine the discriminative utility of CSF AD biomarkers and the selected p-tau threshold in indeterminate cases for predicting response to LDT and shunting. [ABSTRACT FROM AUTHOR]