Magnetic Interactions Between Radical Pairs in Chiral Graphene Nanoribbons.

Open-shell graphene nanoribbons have become promising candidates for future applications, including quantum technologies. Here, we characterize magnetic states hosted by chiral graphene nanoribbons (chGNRs). The substitution of a hydrogen atom at the chGNR edge by a ketone effectively adds one pz electron to the π-electron network, producing an unpaired π-radical. A similar scenario occurs for regular ketone-functionalized chGNRs in which one ketone is missing. Two such radical states can interact via exchange coupling, and we study those interactions as a function of their relative position, which includes a remarkable dependence on the chirality, as well as on the nature of the surrounding ribbon, that is, with or without ketone functionalization. Besides, we determine the parameters whereby this type of system with oxygen heteroatoms can be adequately described within the widely used mean-field Hubbard model. Altogether, we provide insight to both theoretically model and devise GNR-based nanostructures with tunable magnetic properties.

Self-sampling as the principal modality for population based cervical screening: Five-year follow-up of the PaVDaG study.

Self-sampling provides a powerful means to engage women in cervical screening. In the original Papillomavirus Dumfries and Galloway study (PaVDaG), we demonstrated cross-sectional similarity of high-risk human papillomavirus (Hr-HPV) testing on self-taken vaginal vs clinician-taken samples for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+). Few data exist on the longitudinal performance of self-sampling; we present longitudinal outcomes of PaVDaG. Routinely screened women provided a self-taken and a clinician-collected sample. Ninety-one percent of 5136 women from the original cohort completed a further screening round. Sensitivity, specificity, positive predictive value and complement of the negative predictive value of the Hr-HPV test on self-samples for detection of CIN2+ and CIN3+ up-to 5 years after testing were determined. Additionally, clinical accuracy of Hr-HPV testing on vaginal and clinician-collected samples was assessed. A total of 183 CIN2+ and 102 CIN3+ lesions were diagnosed during follow-up. Risk of CIN2+ and CIN3+ following an Hr-HPV negative self-sample was 0.6% and 0.2%, respectively, for up to 5 years after testing. The relative sensitivity for CIN3+ and specificity for ≤CIN1 of Hr-HPV testing on self-taken specimens was slightly lower vs clinician-collected samples: 0.95 (95% CI: 0.90-0.99; PMcN = .0625) and 0.98 (95% CI: 0.95-1.00; PMcN = <.0000), respectively. The low risk of CIN2+ in women with Hr-HPV-self-sample(s) suggests, that the 3 to 5-year recall interval implemented in several cervical screening settings, based on clinician-taken samples, may be safe for self-samples. Future assessment will show if "universal" 5-year screening is appropriate for programs based on self-sampling.

Challenges in the synthesis of corannulene-based non-planar nanographenes on Au(111) surfaces.

The on-surface synthesis of non-planar nanographenes is a challenging task. Herein, with the aid of bond-resolving scanning tunneling microscopy (BRSTM) and density functional theory (DFT) calculations, we present a systematic study aiming at the fabrication of corannulene-based nanographenes via intramolecular cyclodehydrogenation on a Au(111) surface. The formation of non-planar targeted products is confirmed to be energetically unfavorable compared to the formation of planar/quasi-planar undesired competing monomer products. In addition, the activation of intermolecular coupling further inhibits the formation of the final targeted product. Although it was not possible to access the corannulene moiety by means of on-surface synthesis, partial cyclodehydrogenation of the molecular precursors was demonstrated.

Dynamic prediction and identification of cases at risk of relapse following completion of low-intensity cognitive behavioural therapy.

Objective: Low-intensity cognitive behavioural therapy (LiCBT) can help to alleviate acute symptoms of depression and anxiety, but some patients relapse after completing treatment. Little is known regarding relapse risk factors, limiting our ability to predict its occurrence. Therefore, this study aimed to develop a dynamic prediction tool to identify cases at high risk of relapse. Method: Data from a longitudinal cohort study of LiCBT patients was analysed using a machine learning approach (XGBoost). The sample included n = 317 treatment completers who were followed-up monthly for 12 months (n = 223 relapsed; 70%). An ensemble of XGBoost algorithms was developed in order to predict and adjust the estimated risk of relapse (vs maintained remission) in a dynamic way, at four separate time-points over the course of a patient's journey. Results: Indices of predictive accuracy in a cross-validation design indicated adequate generalizability (AUC range = 0.72-0.84; PPV range = 71.2-75.3%; NPV range = 56.0-74.8%). Younger age, unemployment, (non-)linear treatment responses, and residual symptoms were identified as important predictors. Discussion: It is possible to identify cases at risk of relapse and predictive accuracy improves over time as new information is collected. Early identification coupled with targeted relapse prevention could considerably improve the longer-term effectiveness of LiCBT.

A Large Starphene Comprising Pentacene Branches.

Starphenes are attractive compounds due to their characteristic physicochemical properties that are inherited from acenes, making them interesting compounds for organic electronics and optics. However, the instability and low solubility of larger starphene homologs make their synthesis extremely challenging. Herein, we present a new strategy leading to pristine [16]starphene in preparative scale. Our approach is based on a synthesis of a carbonyl-protected starphene precursor that is thermally converted in a solid-state form to the neat [16]starphene, which is then characterised with a variety of analytical methods, such as 13 C CP-MAS NMR, TGA, MS MALDI, UV/Vis and FTIR spectroscopy. Furthermore, high-resolution STM experiments unambiguously confirm its expected structure and reveal a moderate electronic delocalisation between the pentacene arms. Nucleus-independent chemical shifts NICS(1) are also calculated to survey its aromatic character.

Hierarchy in the Halogen Activation During Surface-Promoted Ullmann Coupling.

Within the collection of surface-supported reactions currently accessible for the production of extended molecular nanostructures under ultra-high vacuum, Ullmann coupling has been the most successful in the controlled formation of covalent single C-C bonds. Particularly advanced control of this synthetic tool has been obtained by means of hierarchical reactivity, commonly achieved by the use of different halogen atoms that consequently display distinct activation temperatures. Here we report on the site-selective reactivity of certain carbon-halogen bonds. We use precursor molecules halogenated with bromine atoms at two non-equivalent carbon atoms and found that the Ullmann coupling occurs on Au(111) with a remarkable predilection for one of the positions. Experimental evidence is provided by means of scanning tunneling microscopy and core level photoemission spectroscopy, and a rationalized understanding of the observed preference is obtained from density functional theory calculations.

Protection against ß-amyloid neurotoxicity by a non-toxic endogenous N-terminal ß-amyloid fragment and its active hexapeptide core sequence.

High levels (µM) of beta amyloid (Aß) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C-terminal domain of Aß, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aß at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aß. An N-terminal Aß fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aß-induced impairments of long-term potentiation. Here, we show the impact of this N-terminal Aß fragment and a shorter hexapeptide core sequence in the Aß fragment (Aßcore: 10-15) to protect or reverse Aß-induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N-terminal Aß fragment and Aßcore on Aß-induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108-15) and mouse hippocampal neuron cultures. The protective action of the N-terminal Aß fragment and Aßcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N-terminal Aßcore were also shown to be fully protective against Aß-triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role for the N-terminal Aß fragment, while active stabilized N-terminal Aßcore derivatives offer the potential for therapeutic application.

Effects of Halogen and Hydrogen Bonding on the Electronics of a Conjugated Rotor.

The electronic properties of a pyrazine-containing arylene ethynylene unit are influenced by hydrogen bond and halogen bond donors that are held in proximity of the pyrazine rotor. These interactions are evident with iodine- and bromine-centered halogen bonds and O-H- and C-H-based hydrogen bonds. Bathochromic shifts of UV-vis and fluorescence signals are the best indicators of this intramolecular attraction. The effects can be attenuated in solvents that are less favorable for intramolecular halogen or hydrogen bonding, such as 2-propanol, and amplified in solvents that are supportive, such as toluene. Intramolecular attractions promote planarity in the pyrazine ethynylene system, likely increasing the effective conjugation of the unsaturated backbone. Additionally, computations at the B3LYP and M062X levels of theory using 6-311++G(2d,p) and aug-cc-pVTZ basis sets suggest that the Lewis acidity of the halogen and hydrogen atoms influences electronic behavior even in the absence of conformational constraints.

Two-Dimensional Ketone-Driven Metal-Organic Coordination on Cu(111).

Two-dimensional metal-organic nanostructures based on the binding of ketone groups and metal atoms were fabricated by depositing pyrene-4,5,9,10-tetraone (PTO) molecules on a Cu(111) surface. The strongly electronegative ketone moieties bind to either copper adatoms from the substrate or codeposited iron atoms. In the former case, scanning tunnelling microscopy images reveal the development of an extended metal-organic supramolecular structure. Each copper adatom coordinates to two ketone ligands of two neighbouring PTO molecules, forming chains that are linked together into large islands through secondary van der Waals interactions. Deposition of iron atoms leads to a transformation of this assembly resulting from the substitution of the metal centres. Density functional theory calculations reveal that the driving force for the metal substitution is primarily determined by the strength of the ketone-metal bond, which is higher for Fe than for Cu. This second class of nanostructures displays a structural dependence on the rate of iron deposition.

Risk Determinants of Acute Mountain Sickness and Summit Success on a 6-Day Ascent of Mount Kilimanjaro (5895 m).

OBJECTIVE: The aims of this study were to assess incidence of acute mountain sickness (AMS) and summit success on a 6-day ascent profile of Mt. Kilimanjaro and evaluate potential risk factors for these outcomes. METHODS: All trekkers through a single Australian tour company between August 2012 and July 2014 were included. Participants ascended via the Rongai route and attempted the summit on day 6. Daily assessments were made using the self-reported Lake Louise score (LLS) questionnaire. Two different AMS diagnostic criteria (LLS ≥ 3 and LLS ≥ 5) were used for data analysis. Risk factors for development of AMS and summit success were analyzed. RESULTS: Over the 24-month period a total of 175 participants undertook the trek. Incidence of AMS was 52.6% (LLS ≥ 3) and 22.9% (LLS ≥ 5). Summit success was 88%. Age, sex, body mass index, and acetazolamide use were not associated with risk of AMS development. Age ≥ 40 years (P = .0002) and female sex (P = .0004) were both significantly associated with reduced summit success rate. CONCLUSIONS: Our cohort found a lower incidence of AMS and better summit success on a 6-day ascent of Mt Kilimanjaro than previously described in other groups on 4- and 5-day ascents. Female sex and age ≥ 40 years both predicted failure to summit, but did not increase risk of developing AMS. AMS is a common cause of morbidity on Mt. Kilimanjaro, and although the risk can be mitigated by a slower ascent, there is an ongoing need for education of individual trekkers, tour companies, and local authorities.

Removing divergence of JCGM documents from the GUM ( 1993) and repairing other defects.

The mission of the Joint Committee for Guides in Metrology (JCGM) is to maintain and promote the use of the Guide to the Expression of Uncertainty in Measurement (GUM) and the International Vocabulary of Metrology (VIM, second edition). The JCGM has produced the third edition of the VIM (referred to as VIM3) and a number of documents; some of which are referred to as supplements to the GUM. We are concerned with the Supplement 1 (GUM-S1) and the document JCGM 104. The signal contribution of the GUM is its operational view of the uncertainty in measurement (as a parameter that characterizes the dispersion of the values that could be attributed to an unknown quantity). The operational view promulgated by the GUM had disconnected the uncertainty in measurement from the unknowable quantities true value and error. The GUM-S1 has diverged from the operational view of the uncertainty in measurement. Either the disparities should be removed or the GUM-S1 should not be referred to as a supplement to the GUM. Also, the GUM-S1 has misinterpreted the Bayesian concept of a statistical parameter and the VIM3 definitions of coverage interval and coverage probability are mathematically defective. We offer practical suggestions for revising the GUM-S1 and the VIM3 to remove their divergence from the GUM and to repair their defects.

Regulation of presynaptic Ca2+, synaptic plasticity and contextual fear conditioning by a N-terminal ß-amyloid fragment.

Soluble ß-amyloid has been shown to regulate presynaptic Ca(2+) and synaptic plasticity. In particular, picomolar ß-amyloid was found to have an agonist-like action on presynaptic nicotinic receptors and to augment long-term potentiation (LTP) in a manner dependent upon nicotinic receptors. Here, we report that a functional N-terminal domain exists within ß-amyloid for its agonist-like activity. This sequence corresponds to a N-terminal fragment generated by the combined action of α- and ß-secretases, and resident carboxypeptidase. The N-terminal ß-amyloid fragment is present in the brains and CSF of healthy adults as well as in Alzheimer's patients. Unlike full-length ß-amyloid, the N-terminal ß-amyloid fragment is monomeric and nontoxic. In Ca(2+) imaging studies using a model reconstituted rodent neuroblastoma cell line and isolated mouse nerve terminals, the N-terminal ß-amyloid fragment proved to be highly potent and more effective than full-length ß-amyloid in its agonist-like action on nicotinic receptors. In addition, the N-terminal ß-amyloid fragment augmented theta burst-induced post-tetanic potentiation and LTP in mouse hippocampal slices. The N-terminal fragment also rescued LTP inhibited by elevated levels of full-length ß-amyloid. Contextual fear conditioning was also strongly augmented following bilateral injection of N-terminal ß-amyloid fragment into the dorsal hippocampi of intact mice. The fragment-induced augmentation of fear conditioning was attenuated by coadministration of nicotinic antagonist. The activity of the N-terminal ß-amyloid fragment appears to reside largely in a sequence surrounding a putative metal binding site, YEVHHQ. These findings suggest that the N-terminal ß-amyloid fragment may serve as a potent and effective endogenous neuromodulator.

Energy Consumption and Substrate Utilization During Spinal Surgery.

INTRODUCTION: This study aims to measure surgeon physiologic stress and energy expenditure during adult spine surgery. Energy expenditures were assessed based on patient BMI, lead use, instrumentation/intraoperative navigation, primary/revision surgeries, tranexamic acid (TXA) use, and anatomic region involved. METHODS: The senior author wore a heart rate (HR) monitor and triaxial accelerometer during spinal surgeries, providing assessments of mean HR, maximum HR, calories consumed/minute, and calories as measured by a Polar device (P calories) and Fitbit device (F calories). RESULTS: One hundred sixty-two surgeries were included. Median patient age was 62 years. Median BMI was 29.02. Significant differences existed for BMI and estimated blood loss (P < 0.05). TXA use had a significant effect on case time, estimated blood loss, P calories, F calories, and Kcal/min (P < 0.05). Instrumentation use was significant for all variables (P < 0.05), except for mean HR and Kcal/min (P > 0.05). Lead use did not have a significant effect on max HR, P calories, F calories, and Kcal/min (P > 0.05). Navigation use was associated with significant differences for every variable tested (P ≤ 0.05). Differences were observed between primary and revision surgeries for case time, estimated blood loss, and F calories (P < 0.05). CONCLUSIONS: In spinal surgery, the use of navigation, instrumentation use, TXA use, and performing revision surgeries were associated with increased energy expenditure and can potentially increase surgeon fatigue.

Establishing case volume benchmarks for ACGME-accredited orthopedic surgery of the spine fellowship training.

BACKGROUND CONTEXT: There has been increasing scrutiny on the standardization of surgical training in the US. PURPOSE: This study provides case volume benchmarks for Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopedic spine surgery fellowship training. STUDY DESIGN/SETTING: This was a retrospective cross-sectional study of fellows at ACGME-accredited orthopedic spine surgery fellowships (2017-2022). PATIENT SAMPLE: N/A. OUTCOME MEASURES: Reported case volume during fellowship training. METHODS: Case volume percentiles were calculated across ACGME-defined case categories and temporal changes assessed via linear regression. Variability between the highest and lowest deciles by case volume was calculated as fold-differences (90th percentile/10th percentile). Sensitivity analyses were performed to identify potential targets for case minimum requirements. RESULTS: A total of 163 spine surgery fellows were included in this study. Total mean reported spine surgery case volume increased from 313.2±122 in 2017 to 382.0±164 in 2022 (p=.19). Most cases were classified as adult (range, 97.2%-98.0%) over pediatric cases (range, 2.0%-2.8%). An average of 322.0 cases were reported and most were classified as laminectomy (32%), posterior arthrodesis (29%), and anterior arthrodesis (20%). Overall variability in total case volume was 2.4 and the greatest variability existed for posterior instrumentation (38.1), application of cage (34.6), anterior instrumentation (20.8), and fractures and dislocations (17.3). If case minimum requirements for total reported cases was assumed at 200 cases, then all spine fellows included in this study would achieve this requirement. However, if case minimum requirements were assumed at 250 total cases, then approximately thirty percent of fellows (n=49) would not achieve this requirement for graduation. CONCLUSIONS: Increasingly, national societies and accrediting bodies for surgical education recognize the need for standardized training. This study provides benchmarks to inform potential case minimum requirements and help reduce variability during spine fellowship training. Future studies are needed to establish case minimum requirements for spine surgery fellowship training across comprehensive and granular case categories that cover the full gamut of orthopedic spine surgery.

Patient Resiliency and Caregiver Burden After Traumatic Spinal Cord Injury Resulting in Quadriplegia.

Traumatic spinal cord injury (tSCI) resulting in quadriplegia is a life-altering injury for patients and caregivers. We conducted a retrospective review of patients treated for tSCI and quadriplegia at a level 1 trauma center to assess quality of life (QOL), socioeconomic factors, and mortality. Patients and caregivers were surveyed. Of the 65 patients included, 33 contacts were made. Seventeen surveys were completed (12 caregivers and 5 patients). Six unreachable patients were confirmed alive via medical record. Mortality rate among these 39 accessible patients was 23% (n = 9). Medicaid and uninsured patients experienced longer hospital length of stay (P < .0001) and discharged to home or nursing facilities (P < .0001) more often than those with private insurance or Medicare. Patients reported overall "good" QOL (80%) while caregivers reported overall decreased QOL markers. Our results reflect the resilience among this patient population, but also highlight the impact of this life-altering injury on the caregiver.

Applications of SPECT/CT in the Evaluation of Spinal Pathology: A Review.

BACKGROUND: Accurate identification of pain generators in the context of low back and spine-related pain is crucial for effective treatment. This review aims to evaluate the potential usefulness of single photon emission computed tomography with computed tomography (SPECT/CT) as an imaging modality in guiding clinical decision-making. METHODS: A broad scoping literature review was conducted to identify relevant studies evaluating the use of SPECT/CT in patients with spine-related pain. Studies were reviewed for their methodology and results. RESULTS: SPECT/CT appears to have advantages over traditional modalities, such as magnetic resonance imaging and CT, in certain clinical scenarios. It may offer additional information to clinicians and improve the specificity of diagnosis. However, further studies are needed to fully assess its diagnostic accuracy and clinical utility. CONCLUSIONS: SPECT/CT is a promising imaging modality in the evaluation of low back pain, particularly in cases where magnetic resonance imaging and CT are inconclusive or equivocal. However, the current level of evidence is limited, and additional research is needed to determine its overall clinical relevance. CLINICAL RELEVANCE: SPECT/CT may have a significant impact on clinical decision-making, particularly in cases in which traditional imaging modalities fail to provide a clear diagnosis. Its ability to improve specificity could lead to more targeted and effective treatment for patients with spinal pathology.

A European Bioanalysis Forum recommendation for requiring a context-of-use statement for successful development and validation of biomarker assays.

The European Bioanalysis Forum, alongside key industry stakeholders, has been driving the discussions around the implementation of context-of use for biomarker assays to ensure that these assays are validated appropriately depending on their purpose. Insights into understanding why the implementation of context-of-use in assay strategies has also shown that the key stakeholder, or requester for the biomarker data, is responsible for providing the context-of-use statement for all biomarker assay requests. Experts from across the industry haves repeatedly sought a cross-industry recommended format in which the context-of-use statement could be provided. In this manuscript, the European Bioanalysis Forum suggests a format for this.

The effect of water on gold supported chiral graphene nanoribbons: rupture of conjugation by an alternating hydrogenation pattern.

In the last few years we have observed a breakpoint in the development of graphene-derived technologies, such as liquid phase filtering and their application to electronics. In most of these cases, they imply exposure of the material to solvents and ambient moisture, either in the fabrication of the material or the final device. The present study demonstrates the sensitivity of graphene nanoribbon (GNR) zigzag edges to water, even in extremely low concentrations. We have addressed the unique reactivity of (3,1)-chiral GNR with moisture on Au(111). Water shows a reductive behaviour, hydrogenating the central carbon of the zigzag segments. By combining scanning tunnelling microscopy (STM) with simulations, we demonstrate how their reactivity reaches a thermodynamic limit when half of the unit cells are reduced, resulting in an alternating pattern of hydrogenated and pristine unit cells starting from the terminal segments. Once a quasi-perfect alternation is reached, the reaction stops regardless of the water concentration. The hydrogenated segments limit the electronic conjugation of the GNR, but the reduction can be reversed both by tip manipulation and annealing. Selective tip-induced dehydrogenation allowed the stabilization of radical states at the edges of the ribbons, while the annealing of the sample completely recovered the original, pristine GNR.

Microfluidic multi-input reactor for biocatalytic synthesis using transketolase.

Biocatalytic synthesis in continuous-flow microreactors is of increasing interest for the production of specialty chemicals. However, the yield of production achievable in these reactors can be limited by the adverse effects of high substrate concentration on the biocatalyst, including inhibition and denaturation. Fed-batch reactors have been developed in order to overcome this problem, but no continuous-flow solution exists. We present the design of a novel multi-input microfluidic reactor, capable of substrate feeding at multiple points, as a first step towards overcoming these problems in a continuous-flow setting. Using the transketolase-(TK) catalysed reaction of lithium hydroxypyruvate (HPA) and glycolaldehyde (GA) to l-erythrulose (ERY), we demonstrate the transposition of a fed-batch substrate feeding strategy to our microfluidic reactor. We obtained a 4.5-fold increase in output concentration and a 5-fold increase in throughput compared with a single input reactor.

Allergic contact dermatitis to Dermabond Prineo after abdominal wound closure for anterior lumbar interbody fusion: case report.

Background: Dermabond Prineo is popular for wound closure due to its anti-microbial attribute, ease of application, and patient comfort. Reports of allergic contact dermatitis have increased, likely due to increased usage, mostly in breast augmentations and joint replacements. To the authors' knowledge, this is the first report of allergic contact dermatitis following spine surgery. Case Description: This case involved a 47-year-old male with a history of two posterior L5-S1 lumbar microdiscectomies. Dermabond Prineo was used in the revision microdiscectomy with no skin complications noted. Six weeks after revision microdiscectomy, the patient underwent discectomy and anterior lumbar interbody fusion of L5-S1, again closed with Dermabond Prineo. One week later, the patient presented with allergic contact dermatitis around his incision, which was treated with topical hydrocortisone and diphenhydramine. Around the same time, he was diagnosed with post-operative pneumonia. Conclusions: Previous studies have suggested that repeated usage and duplicate coverage with 2-octyl cyanoacrylate (Dermabond Prineo) correlate with an increased risk of allergic reaction. Type IV hypersensitivity reactions require an initial sensitization to the allergen and subsequent re-exposure for reaction. In this case, the revision microdiscectomy closed with Dermabond Prineo functioned as the sensitization and repeated usage in a subsequent discectomy caused an allergic reaction. Providers should be aware of the increased risk of allergic reaction when using Dermabond Prineo for repeat surgeries.