bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Methylene-Bridged Trifluoromethyl Azoles Using 5-(1,2,3-Triazol-1-yl)enones
Authors: Zanatta Nilo , Mittersteiner Mateus , Aquino Estefania C. , Budragchaa Tuvshinjargal , Wessjohann Ludger A. , Bonacorso Helio G. , Martins Marcos A. P.
Published: October 2021

A protocol for synthesizing triazole-containing pyrazolines and pyrazoles selectively using trifluoromethylated 5-(1,2,3-triazol-1-yl)enones as starting materials, is reported. The selectivity of the reaction was controlled by the nature of the hydrazine or derivative used: free hydrazines furnished the 1,5-regiosiomer exclusively in yields up to 98%, whereas protected hydrazines provided the 1,3-regioisomer in yields up to 77%. To demonstrate the synthetic versatility of the triazole-based enone, reactions with other unsymmetrical dinucleophiles (hydroxylamine hydrochloride and S-methyl isothiourea sulfates) allowed the selective preparation of triazole-containing isoxazoline and pyrimidine rings.
Lengths of Stay and Discharge Dispositions after Total Knee Arthroplasty: A Comparison of Robotic-Assisted and Manual Techniques
Authors: Archer Allison , Salem Hytham S. , Coppolecchia Andrea , Mont Michael A.
Published: October 2021

As evidence signifies that short-stay total knee arthroplasties (TKA) can be safe options, it is important to identify factors that contribute to early discharge. There is evidence that robotic-assisted TKAs may lead to shorter lengths of postoperative stays. However, this has not been evaluated as the primary outcome of interest in a large-scale population. The purpose of this study was to compare manual and robotic-assisted TKAs with regard to: (1) length of stay (LOS) and (2) discharge dispositions. TKAs performed between January 1, 2018, to March 31, 2019, were identified. After applying inclusion and exclusion criteria, a total of 10,296 patients were included: 5,993 in the manual and 4,303 in the robotic-assisted group. Length of stay, discharge dispositions, and Charlson comorbidity indices (CCIs) were recorded for all patients. The mean LOS was significantly lower in robotic-assisted (1.68 ± 0.86 days) compared with manual (1.86 ± 0.94 days) TKA procedures (p < 0.00001). In the robotic-assisted group, 2,049 (47.6%) were discharged in 1 day or less compared with 2,325 (38.8%) in the manual group (p < 0.0001). The proportion discharged home was significantly higher for patients who underwent robotic-assisted (91.3%) compared with manual (87.4%) TKAs (p < 0.00001). When comparing only patients who were discharged home and who did not have home health services, the rate was 51.8% in the robotic-assisted group compared with 44.0% in the manual group (p < 0.00001). The mean CCI was similar for patients who underwent robotic-assisted (2.9 ± 1.4 points) compared with manual (3.0 ± 1.5 points) TKAs. There was a trend toward shorter mean LOS for robotic-assisted versus manual TKA at 17 of the 24 included hospital sites (70.8%). Compared with manual, robotic-assisted TKAs demonstrated shorter lengths of postoperative stays and less need for skilled care after discharge. These results suggest the health care burden resulting from an upsurge of TKA procedures in our aging population might be addressed in part by increased utilization of robotic assistance.
Magnetic Resonance Arthrography of the Wrist: The Impact on Operative Management of Wrist Injuries
Authors: Lee Glenn E. , Forster Grace L. , Freilich Aaron M. , DeGeorge Brent R.
Published: October 2021

Background There is no consensus on the utility of arthrography in the evaluation of wrist injuries. This study evaluates ordering trends of different types of magnetic resonance imaging (MRI) of the wrist and compares rates of surgery following these imaging modalities.

Methods A national claims-based database was used to identify patients who underwent MRI within 90 days of a first-instance diagnosis of wrist injury from 2010 to 2018. The utilization of MRI without intravenous (IV) contrast, MRI with IV contrast, and MRI with arthrogram was investigated. The instances of operative procedures of the wrist within 1 year of MRI study were recorded. Patient demographics, comorbidities, type of operative procedure, and ordering physician specialty were obtained. Logistic regression analysis was used to evaluate the utilization of MRI and subsequent 1-year operative intervention rates as well as association of patient-related factors.

Results Magnetic resonance arthrography use was associated with higher rates of subsequent operative treatment. Surgeons were more likely to order an arthrogram at the time of MRI. Younger patients were more likely to undergo MRI-based advanced imaging.

Conclusion Surgeons may perceive MRA of the wrist to play an important role in operative decision-making following wrist injury.

Level of Evidence This is a Level III, retrospective cohort study.
Fourth-Generation Total Wrist Arthroplasty: A Systematic Review of Clinical Outcomes
Authors: Zijlker Hero Jan Aeilko , Ritt Mathias Joseph Petrus Franciscus , Beumer Annechien
Published: October 2021

Background The purpose of total wrist arthroplasty is to reduce pain and maintain mobility in a painful destructed wrist. First-, second-, and third-generation total wrist arthroplasties have shown unacceptable outcomes with high failure rates. In 2004, the fourth-generation total wrist implants were introduced to address the clinical problems encountered in the previous generations of total wrist implants.

Methods Outcomes and complications of fourth-generation total wrist implants were systematically reviewed in the literature (2004–present), including the Universal 2, ReMotion, Freedom, Motec, and Maestro total wrist implants.

Results The literature search yielded 114 papers, of which 18 (990 implants) were included in this systematic review. The quality of evidence was low. All implants effectively reduced pain and improved functionality of the wrist. The Motec wrist implant demonstrated the highest survival rate at 10 year follow-up (86%).

Conclusion This systematic review suggests a substantial improvement of quality in fourth-generation total wrist arthroplasty.
Allinside Anatomic Arthroscopic (3A) Reconstruction of Irreparable TFCC Tear
Authors: Atzei Andrea , Tandioy-Delgado Fabio Andrés , Marcovici Lucian Lior , Aust Thomas W. , Luchetti Riccardo
Published: October 2021

Background In recent years, new arthroscopic techniques have been introduced to address the irreparable tears of the triangular fibrocartilage complex (TFCC) (Palmer type 1B, Atzei class 4) by replicating the standard Adams–Berger procedure. These techniques, however, show the same limitations of the open procedure in relation to the anatomically defective location of the radial origins of the radioulnar ligaments (RUL) and the risk of neurovascular and/or tendon injury. Aiming to improve the quality of reconstruction and reduce surgical morbidity, a novel arthroscopic technique was developed, with the advantages of reproducing the anatomical origins of the RUL ligaments and providing all-inside tendon graft (TG) deployment and fixation.

Description of Technique The Allinside anatomic arthroscopic (3A) technique is indicated for TG reconstruction of irreparable TFCC tears in the absence of distal radioulnar joint (DRUJ) arthritis. Standard wrist arthroscopy portals are used. A small incision in the radial metaphyseal area and arthroscopic control are required to set a Wrist Drill Guide and create two converging tunnels, whose openings are at the radial anatomical origins of the RUL. An ulnar tunnel is drilled at the fovea from inside-out via the 6U portal. A 3-mm tendon strip, from the palmaris longus or extensor carpi radialis brevis, is woven through the tunnels and then secured into the ulnar tunnel with an interference screw. Postoperative immobilization with restricted forearm rotation is discontinued at 5 weeks, and then postoperative rehabilitation is started.

Patients and Methods The 3A technique was applied on 5 patients (2 females and 3 males), with an average age 42 years. DRUJ stability, range of motion (ROM), pain (0–10 visual analogue scale [VAS]), grip strength, modified Mayo wrist score (MMWS), and patient satisfaction were used for evaluation before surgery and at follow-up.

Results No intraoperative or early complications were registered. At a mean follow-up of 26 months, DRUJ was stable in all patients, which recovered 99% ROM. Pain VAS decreased from 7 to 0.6. Grip strength increased from 38 to 48.8 Kgs. There were 4 excellent results and 1 good result on MMWS. All patient showed high satisfaction.

Conclusions Although the 3A technique requires dedicated instrumentation and arthroscopic expertise, it takes advantage of improved intra-articular vision and minimized surgical trauma to reduce the risk of complications and obtain promising functional results.
Risk Factors for Readmission following Anterior Cruciate Ligament Reconstruction
Authors: Best Matthew J. , Harris Andrew B. , Marrache Majd , Martin Scott D. , Rue John-Paul H. , Wilckens John H.
Published: October 2021

The purpose of this study is to identify risk factors for readmission after anterior cruciate ligament (ACL) reconstruction and to determine costs associated with readmission. Using a private insurance claims' database, we identified patients who underwent ACL reconstruction from 2010 to 2015 using the International Classification of Diseases, Version 9 (ICD-9) and Current Procedural Terminology (CPT) codes. Univariate analysis was performed on demographic data, surgical characteristics, and comorbidities. Variables with p < 0.10 were added to a multivariate logistic regression model which was created to identify independent risk factors for all-cause readmission within 90 days postoperatively. Significance was considered at p < 0.05. Overall, 90,263 patients were included (average age: 29 ± 13 years, 44% female), and 1,066 (1.2%) of patients had a hospital readmission within 90 days following surgery. Risk factors for hospital readmission included cerebrovascular disease (odds ratio [OR] = 3.4, 95% confidence interval [CI]: 1.9, 6.2), diabetes mellitus (OR = 2.6, 95% CI: 1.9, 3.5), concomitant medial collateral ligament (MCL) or lateral collateral ligament (LCL) reconstruction (OR = 2.5, 95% CI: 1.9, 3.3), concomitant posterior cruciate ligament (PCL) reconstruction (OR = 2.2, 95% CI: 1.4, 3.3), age between 44 and 65 years (OR = 2.1, 95% CI: 1.6, 2.9), and depression (OR = 1.88, 95% CI: 1.49, 2.38, p < 0.001). Female sex was associated with decreased odds of 90-day hospital readmission (OR = 0.8, 95% CI: 0.7, 0.9). Each hospital readmission accounted for an estimated $17,841 (95% CI: $17,173, 18,509) in gross health care payments, and patients with readmissions had substantially higher 1-year cumulative health care costs. Readmission after ACL reconstruction was 1.2%. The strongest risk factors for 90-day readmission include cerebrovascular disease, diabetes mellitus, concomitant MCL/LCL reconstruction, concomitant PCL reconstruction, and age between 44 and 65 years. Readmission was associated with substantial health care costs.
Water-based devices for advanced control of electromagnetic waves
Authors: Jacobsen Rasmus E. , Arslanagić Samel , Lavrinenko Andrei V.
Published: October 2021

Tunable devices are of great interest as they offer reconfigurability to their operation, although many of them employ rare and expensive materials. In a world with increasing focus on ecological compatibility and recyclability, immense efforts are being made to find bio-friendly alternatives. However, in some cases, one does not have to look far, because water, a high-permittivity dielectric at microwave frequencies, is readily available. Recent studies have shown that compact Mie resonators, which are the fundamental blocks in all-dielectric metamaterials and dielectric resonator antennas, can be realized with small water elements. In a variety of applied physics areas, encompassing frequencies from the radio to the optical parts of the spectrum, all-dielectric implementations have received immense attention. When it comes to water, its temperature-dependent permittivity and liquidity enable a multitude of unprecedentedly simple means to reconfigure and tune the resulting devices. Moreover, being a polar solvent, water easily dissolves various physiologically important electrolytes, which potentially can be exploited in a sensor design. Presently, we review water-based devices for advanced microwave control and sensing. We show and discuss the dynamic properties of water and examine the microwave scattering and absorption characteristics of single water elements. We investigate how such water elements can be employed in various microwave designs, including single resonators, metamaterials, metasurfaces, antennas, absorbers, and radio frequency components. The main complications of water are its losses, especially at higher microwave frequencies, and its stability. We discuss how to overcome these and show that even highly loss-sensitive modes, namely, toroidal modes and bound states in the continuum, can be realized with water-based devices. We believe that water-based devices usher the route to meet the UN proclaimed goals on global sustainability and human-friendly environment.
Protocol for temperature sensing using a three-level transmon circuit
Authors: Sultanov Aidar , Kuzmanović Marko , Lebedev Andrey V. , Paraoanu Gheorghe Sorin
Published: October 2021

We present a method for in situ temperature measurement of superconducting quantum circuits, by using the first three levels of a transmon device to which we apply a sequence of π gates. Our approach employs projective dispersive readout and utilizes the basic properties of the density matrix associated with thermal states. This method works with an averaging readout scheme and does not require a single-shot readout setup. We validate this protocol by performing thermometry in the range of 50–200 mK, corresponding to a range of residual populations 1%–20% for the first excited state and 0.02%–3% for the second excited state.
Enhanced air stability of ridged superhydrophobic surface with nanostructure
Authors: Heo Seongkwang , Choi Woorak , Lee Sang Joon
Published: October 2021

Air plastron in a superhydrophobic (SHPo) surface works as a lubricant that induces drag reduction on the surface. By air plastron, air is trapped between structures of the SHPo surface. However, air plastron is easily depleted by static water pressure or external flow conditions. Various nanostructures have been introduced to enhance the air stability of SHPo surfaces. In this study, the effects of such nanostructure on the air stability were experimentally investigated under high water pressure and flow conditions. Polyvinyl chloride solution was employed to form the nanostructure on the ridged SHPo surface. The critical pressure for the depletion of air plastron is 70% higher on SHPo surfaces introduced with the nanostructure than on surfaces without the nanostructure. Pressure drops (ΔP) in rectangular channels with the SHPo surface on the bottom side were measured to quantify the air stability under a flow condition. ΔP gradually decreases as the air plastron disappears on both SHPo surfaces. The hierarchical ridged surfaces with the nanostructure showed better air stability under static and flow conditions compared with the simple ridged surfaces without the nanostructure. The present results are helpful to understand the effects of the nanostructure on the air stability and its drag reduction mechanism.
Mechanism and experimental study of arc suppression by polyphase longitudinal airflow
Authors: Li Zijian , Zhou Xueming , Feng Zhiqiang , Zhang Yaodong , hu Danhui , Wang Jufeng
Published: October 2021

An arc extinguishing lightning protection device with a multi-arc extinguishing chamber structure has been gradually applied to the overhead line lightning protection, but the process and key factors of the arc building of the internal multi-phase flow suppression arc still need to be studied. In this paper, based on the theory of arc magnetohydrodynamics and Euler’s high velocity flow field model, a simplified model of arc coupled polyphase longitudinal air flow in a multi-pipe structure is established, the approximate solution of the model is made, and the development process of polyphase air flow and the extinction mechanism of the arc are obtained. At the same time, the arc quenching process of polyphase longitudinal air flow is also studied experimentally. The experimental results show that the continuous arc of power frequency can be stopped quickly and will not be reignited under the condition of polyphase air flow.
Prolific or precarious: a review of the status of Australian sandalwood (
Authors: McLellan R. C. , Dixon K. , Watson D. M.
Published: October 2021

Across its entire range in Australia’s western and southern rangelands, Australian sandalwood (Santalum spicatum [R.Br.] A.DC.) is on a path towards ‘extinction in the wild’––the International Union for the Conservation of Nature’s penultimate category of conservation risk. Sandalwood populations have substantially diminished or become locally extinct, predominantly a consequence of land clearing for agriculture, introduced grazers, disruption of key ecological processes (e.g. seed dispersal, fire regimes) and 175 years of intensive commercial exploitation for its fragrant, high value timber. The status of the world’s last wild-harvested species of sandalwood is significant to both conservation and rangeland management, and the implementation of a science-based sustainable yield approach to management of this species is vital. By highlighting the scale and precipitous rate of decline and identifying key drivers affecting mortality and recruitment, this review outlines the conservation and restoration needs of the species in situ to conserve remaining wild populations, and the need to transition to science-based resource management actions such as farm-based plantation production.
Competing magnetic interactions and magnetocaloric effect in Ho5Sn3
Authors: Mondal Suman , Yadav Pushpendra , Sarkar Anan Bari , Dutta Prabir , Giri Saurav , Agarwal Amit , Majumdar Subham
Published: October 2021

The rare-earth intermetallic compound Ho5Sn3 demonstrates fascinating magnetic properties, which include temperature-driven multiple magnetic transitions and field-driven metamagnetism. We address the magnetic character of this exciting compound through a combined experimental and theoretical studies. Ho5Sn3 orders antiferromagnetically below 28 K, and shows further spin reorientation transitions at 16 K and 12 K. We observe a sizable amount of low-temperature magnetocaloric effect (MEC) in Ho5Sn3 with a maximum value of entropy change ΔS = −9.5 J Kg−1 K−1 for an applied field of H = 50 kOe at around 30 K. The field hysteresis is almost zero above 15 K where the MEC is important. Interestingly, ΔS is found to change its sign from positive to negative as the temperature is increased above about 8 K, which can be linked to the multiple spin reorientation transitions. The signature of the metamagnetism is visible in the ΔS versus H plot. The magnetic ground state, obtained from the density functional theory based calculation, is susceptible to the effective Coulomb interaction (U
eff) between electrons. Depending upon the value of U
eff, the ground state can be ferromagnetic or antiferromagnetic. The compound shows large relaxation (14% change in magnetisation in 60 min) in the field cooled state with a logarithmic time variation, which may be connected to the competing magnetic correlations observed in our theoretical calculations. The competing magnetic ground states are equally evident from the small value of the paramagnetic Curie–Weiss temperature.
1T MoS2 growth from exfoliated MoS2 nucleation as high rate anode for sodium storage
Authors: Xu Zhanwei , Liu Xinyue , Yao Kai , Ren Yuchuan , Li Jiayin , Shen Xuetao , Li Zhi
Published: October 2021

Recently, metallic 1T MoS2 has been investigated due to its excellent performance in electrocatalysts, photocatalysts, supercapacitors and secondary batteries. However, there are only a few fabrication methods to synthesize stable 1T MoS2. In this work, exfoliated MoS2 is employed as seed crystals for the nucleation and growth of a stable 1T MoS2 grains by an epitaxial growth strategy. The 1T MoS2 displays a large interlayer spacing around 0.95 nm, excellent hydrophilia and more electrochemically active sites along the basal plane, which contribute an efficient ion/electron transport pathway and structural stability. When employed as the anode material for sodium ion batteries, the 1T MoS2 electrodes can survive 500 full charge/discharge cycles with a minimum capacity loss of 0.40 mAh g−1 cycle−1 tested at a current density of 1.0 A g−1, and the capacity degradation is as low as 0.39 mAh g−1 cycle−1 at a current density of 2.0 A g−1.
Fabrication of Cu(II) oxide-hydroxide nanostructures onto graphene paper by laser and thermal processes for sensitive nano-electrochemical sensing of glucose
Authors: Scandurra Antonino , Censabella Maria , Boscarino Stefano , Condorelli Guglielmo Guido , Grimaldi Maria Grazia , Ruffino Francesco
Published: October 2021

Glucose electrochemical sensors based on nanostructures of CuO/Cu(OH)2 onto graphene paper were prepared by thermal (solid) and nanosecond pulsed laser (molten phase) dewetting of a CuO layer 6 nm thin deposited by sputtering. Dewetted systems, obtained without the use of any binder, act as array of nanoelectrodes. Solid state and molten phase dewetting produce nanostructures of copper oxide-hydroxide with different average size, shape and surface composition. Molten phase dewetting originates particles with size below 100 nm, while solid state dewetting produces particles with average size of about 200 nm. Moreover, molten phase dewetting produce drop-shaped nanostructures, conversely nanostructures derived from solid state dewetting are multifaceted. X-ray photoelectron spectroscopy (XPS) characterization revealed that the surface of nanostructures is formed by a copper(II) species CuO and Cu(OH)2. Shape of anodic branch of the cyclic voltammograms of glucose in alkali solution evidenced a convergent diffusion mechanism. Analytical performances in amperometric mode are as good as or better than other sensors based on copper oxide. Amperometric detection of glucose was done at potential as low as 0.4 V versus saturated calomel electrode by both types of electrodes. Linear range from 50 μM to 10 mM, sensitivity ranging from 7 to 43 μA cm−2 mM−1 and detection limit of 7 μM was obtained. Good analytical performances were obtained by laser dewetted electrodes with a low copper content up to 1.2 by atoms percentage of the surface. Analytical performance of the proposed electrodes is compliant for the determination of glucose both in blood serum, saliva or tear.
RETRACTED: Research on Computer Information Processing Technology from the Perspective of the Big Data Era
Authors: Li Jinmeng
Published: October 2021

With the development of China's social economy and science and technology, the computer age is also developing rapidly. Nowadays, the development and progress of society is inseparable from the application of computer network technology. At the same time, the development of Internet technology has enabled us to enter the big data society a long time ago. Information technology not only promotes the development of society, but also computer technology is very important to people's lives, so the number of computer users is very large at present. It is not easy to deal with big data due to its huge quantity, complex form and unstructured characteristics, which often requires analysts to have a high reserve of relevant knowledge such as statistics and computer technology.
Finite propagation enhances Turing patterns in reaction–diffusion networked systems
Authors: Carletti Timoteo , Muolo Riccardo
Published: October 2021

We hereby develop the theory of Turing instability for reaction–diffusion systems defined on complex networks assuming finite propagation. Extending to networked systems the framework introduced by Cattaneo in the 40s, we remove the unphysical assumption of infinite propagation velocity holding for reaction–diffusion systems, thus allowing to propose a novel view on the fine tuning issue and on existing experiments. We analytically prove that Turing instability, stationary or wave-like, emerges for a much broader set of conditions, e.g., once the activator diffuses faster than the inhibitor or even in the case of inhibitor–inhibitor systems, overcoming thus the classical Turing framework. Analytical results are compared to direct simulations made on the FitzHugh–Nagumo model, extended to the relativistic reaction–diffusion framework with a complex network as substrate for the dynamics.
A uniqueness result for self-expanders with small entropy
Authors: Yao Junfu
Published: October 2021

In this short note, we prove a uniqueness result for small entropy self-expanders asymptotic to a fixed cone. This is a direct consequence of the mountain-pass theorem and the integer degree argument proved by J. Bernstein and L. Wang.
iNucs: inter-nucleosome interactions
Authors: Oveisi Mehrdad , Shukla Manu , Seymen Nogayhan , Ohno Masae , Taniguchi Yuichi , Nahata Sunil , Loos Remco , Mufti Ghulam J , Allshire Robin C , Dimitrov Stefan , Karimi Mohammad M
Published: October 2021

Motivation

Deciphering nucleosome–nucleosome interactions is an important step toward mesoscale description of chromatin organization but computational tools to perform such analyses are not publicly available.

Results

We developed iNucs, a user-friendly and efficient Python-based bioinformatics tool to compute and visualize nucleosome-resolved interactions using standard pairs format input generated from pairtools.

Availabilityand implementation

https://github.com/Karimi-Lab/inucs/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Profiling PI3K-AKT-MTOR variants in focal brain malformations reveals new insights for diagnostic care
Authors: Pirozzi Filomena , Berkseth Matthew , Shear Rylee , Gonzalez Lorenzo , Timms Andrew E , Sulc Josef , Pao Emily , Oyama Nora , Forzano Francesca , Conti Valerio , Guerrini Renzo , Doherty Emily S , Saitta Sulagna C , Lockwood Christina M , Pritchard Colin C , Dobyns William B , Novotny Edward , Wright Jason N N , Saneto Russell P , Friedman Seth , Hauptman Jason , Ojemann Jeffrey , Kapur Raj P , Mirzaa Ghayda M
Published: October 2021

Focal malformations of cortical development including focal cortical dysplasia, hemimegalencephaly and megalencephaly, are a spectrum of neurodevelopmental disorders associated with brain overgrowth, cellular and architectural dysplasia, intractable epilepsy, autism and intellectual disability. Importantly, focal cortical dysplasia is the most common cause of focal intractable paediatric epilepsy. Gain and loss of function variants in the PI3K-AKT-MTOR pathway have been identified in this spectrum, with variable levels of mosaicism and tissue distribution. In this study, we performed deep molecular profiling of common PI3K-AKT-MTOR pathway variants in surgically resected tissues using droplet digital polymerase chain reaction (ddPCR), combined with analysis of key phenotype data. A total of 159 samples, including 124 brain tissue samples, were collected from 58 children with focal malformations of cortical development. We designed an ultra-sensitive and highly targeted molecular diagnostic panel using ddPCR for six mutational hotspots in three PI3K-AKT-MTOR pathway genes, namely PIK3CA (p.E542K, p.E545K, p.H1047R), AKT3 (p.E17K) and MTOR (p.S2215F, p.S2215Y). We quantified the level of mosaicism across all samples and correlated genotypes with key clinical, neuroimaging and histopathological data.

Pathogenic variants were identified in 17 individuals, with an overall molecular solve rate of 29.31%. Variant allele fractions ranged from 0.14 to 22.67% across all mutation-positive samples. Our data show that pathogenic MTOR variants are mostly associated with focal cortical dysplasia, whereas pathogenic PIK3CA variants are more frequent in hemimegalencephaly. Further, the presence of one of these hotspot mutations correlated with earlier onset of epilepsy. However, levels of mosaicism did not correlate with the severity of the cortical malformation by neuroimaging or histopathology. Importantly, we could not identify these mutational hotspots in other types of surgically resected epileptic lesions (e.g. polymicrogyria or mesial temporal sclerosis) suggesting that PI3K-AKT-MTOR mutations are specifically causal in the focal cortical dysplasia-hemimegalencephaly spectrum. Finally, our data suggest that ultra-sensitive molecular profiling of the most common PI3K-AKT-MTOR mutations by targeted sequencing droplet digital polymerase chain reaction is an effective molecular approach for these disorders with a good diagnostic yield when paired with neuroimaging and histopathology.
New developments for dietary treatment of epilepsy after a century of history for the ketogenic diet
Authors: Auvin Stéphane
Published: October 2021

This scientific commentary refers to ‘The link between brain acidosis, breathing, and seizures: a novel mechanism of action for the ketogenic diet in a model of infantile spasms’ by Choudhary et al. (https://doi.org/10.1093/braincomms/fcab189) and ‘K.Vita: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy’ by Schoeler et al. (https://doi.org/10.1093/braincomms/fcab160)
Determination of B Vitamins by Double-Vortex-Ultrasonic Assisted Dispersive Liquid–Liquid Microextraction and Evaluation of their Possible Roles in Susceptibility to COVID−19 Infection: Hybrid Box–Behnken Design and Genetic Algorithm
Authors: Akbari Akbar , Koolivand Zahra , Mohamadi Mohamad Bagher , Zahedi Atefeh , Ghasemnezhad Masoumeh , Sabati Zolfaghar , Chamkouri Narges
Published: October 2021

Objectives

In this study, double-vortex-ultrasonic assisted dispersive liquid–liquid microextraction (DVUDLLME) was applied to determine the concentration of vitamin B9, 5-methyl tetrahydrofolate (5-MeTHF) and vitamin B12 in human serum samples.

Methods

High-performance liquid chromatography (HPLC) coupled with DVUDLLME was applied to analyze vitamins B in patients with Coronavirus disease (COVID-19). Then, significant variables were chosen and optimized using the hybrid Box–Behnken design and genetic algorithm.

Results

The detection limits of DVUDLLME–HPLC were 0.21 ng mL−1, 0.18 ng mL−1 and 55 pgmL−1 for vitamin B9, 5-MeTHF and vitamin B12, respectively. Subsequently, DVUDLLME-HPLC was applied to measure B vitamins and investigated their possible roles in susceptibility to COVID-19 infection. Fifty-seven percent of the patients without an underlying disease have significantly lower serum vitamin B12 levels in comparison to controls.

Conclusions

The advantages of this method are low detection limit, simple preparation, low retention time and the use of a cheaper technique instead of expensive mass detectors. The results suggest that vitamin B12 deficiency may decrease the immune system defenses against COVID-19 patients without an underlying disease and cause the disease to become severe. However, these works need a large population and further research, such as a randomized trial and a cohort study.
Development and internal validation of a Wasp Sting Severity Score to assess severity and indicate blood purification in persons with Asian wasp stings
Authors: Liu Yong , Shu Hongmei , Long Youlin , Nie Xiaoqin , Tang Hongfu , Tu Lang , Zhang Hao , Qiu Gang , He Daihua , Huang Qiang , Zhang Qi , Qing Shuang , Xu Donglin , Xia Hongtao
Published: October 2021

Background

In recent years, the incidence of wasp sting has increased annually in China. Organ damage and high mortality due to mass wasp envenomation remain major challenges. Timely and appropriate medical intervention can improve survival. However, there are currently no normalized tools for early assessment of severity.

Methods

The clinical data of wasp sting patients hospitalized from 2011 to 2019 were used as a training set. Logistic regression was used to explore major risk factors for the development of a severe case of wasp sting (SC). The Wasp Sting Severity Score (WSS) was determined considering these risk factors to identify SCs and was tested in a validation dataset that was prospectively collected in 2020.

Results

The data of 1131 wasp sting patients from 2011 to 2019 were included in the training set. Logistic regression analysis showed that tea-colored urine, number of stings, and lactate dehydrogenase and total bilirubin levels were risk factors for developing an SC. The WSS was developed considering these four risk factors, and the total possible WSS was 20 points. The WSS was tested using the validation dataset, comprising the data of 153 patients, in 2020, and we found that a WSS ≥3 points was an important indication for blood purification, with a sensitivity of 71.9%, specificity of 92.6% and an area under the curve of 0.918 (95% confidence interval 0.873–0.962). Among patients with more than 30 stings, mortality in those who underwent plasma exchange (PE) within 24 h after admission was significantly lower than that in those who did not receive PE treatment (14.3% versus 46.9%, P = 0.003). However, continuous venovenous hemofiltration (CVVH) (P = 0.317) and hemoperfusion (HP) (P = 0.869) did not significantly reduce mortality.

Conclusions

Patients with WSS scores ≥3 should be considered for blood purification as early as possible in addition to routine treatment. In addition, PE is better than CVVH and HP at reducing mortality in patients suffering from severe wasp stings.
Sex-Specific Absolute Delta Thresholds for High-Sensitivity Cardiac Troponin T
Authors: Liu Li , Consagra William , Cai Xueya , Mathias Andrew , Worster Andrew , Ma Jinhui , Rock Philip , Kwong Tai , Kavsak Peter A
Published: October 2021

Background

Sex differences in high-sensitivity cardiac troponin (hs-cTn) concentrations from healthy populations have led to the establishment of sex-specific upper reference limits for hs-cTn assays. This study assessed the performance of sex-specific delta (i.e., changes in concentrations) thresholds for the hs-cTnT assay for ruling in acute myocardial infarction (AMI) in different emergency department (ED) populations.

Methods

This retrospective study consisted of 2 cohorts (Cohort 1 derivation and Cohort 2 validation). Cohort 1 consisted of 18 056 ED patients who had serial hs-cTnT measured using a 0-h/3-h algorithm at a US medical center, with Cohort 2 consisting of 1137 ED patients with 0-h/3-h sampling at a Canadian medical center. The primary outcome was AMI diagnosis with sex-specific deltas derived based on the Youden index and specificity estimates (i.e., ≥90%) in Cohort 1 and validated in Cohort 2.

Results

In Cohort 1, 42% of all patients had 0-h hs-cTnT above the sex-specific 99th percentile. Males had higher 0-h hs-cTnT (median 17 ng/L) and absolute deltas (median 2 ng/L) than females (0-h median 11 ng/L, P < 0.0001; deltas median 1 ng/L, P < 0.0001) in non-AMI patients but not in patients with AMI. For ruling in AMI, the sex-specific delta thresholds based on 90% specificity (14 ng/L for males, 11 ng/L for females) performed best and resulted in 91% diagnostic accuracy in both males and females. The sex-specific delta thresholds yielding high specificity estimates were confirmed in the validation data set.

Conclusions

Sex-specific absolute delta thresholds can be used to rule in AMI and are robust across different study populations.
Safeguarding Freedom? Liberty Protection Safeguards, Social Justice and the Rule of Law
Authors: Harding Rosie
Published: October 2021

The issue of when and how disabled people can be lawfully deprived of their liberty is a major contemporary challenge for mental capacity law. People who lack capacity to consent to treatment that deprives them of their liberty must have access to safeguards to protect their rights under Article 5 ECHR. The current Deprivation of Liberty Safeguards are widely considered to be unfit for purpose, and a replacement scheme, the ‘Liberty Protection Safeguards’ (LPS) were proposed by the Law Commission of England and Wales in 2017. These safeguards were legislated for in 2018/19 in the Mental Capacity (Amendment) Act and are expected to be implemented in 2022. At the time the reforms were being debated in Parliament, multiple stakeholders expressed serious reservations about the proposals, some going so far as to claim that they are not ‘good law’. In this paper, I evaluate to what extent the LPS is (or has the potential to be) ‘good law’, drawing on two contrasting conceptual frameworks to guide that analysis: Bingham’s (2007) sub-principles of the rule of law; and the capabilities approach developed by Sen and Nussbaum (among others). I argue that despite the technical problems with the legislation that caused such concern during its passage through parliament, if the implementation process is grounded in a strong social justice conceptual frame, the LPS has the potential to be a positive legal reform.
Comparing echocardiographic characteristics in genotype positive–phenotype positive hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy
Authors: de la Rosa Angelo , Shah Maulin , Shiota Takahiro , Siegel Robert , Rader Florian
Published: October 2021

Aims

There is little information about hypertrophic cardiomyopathy (HCM) with pathologic genetic mutations and concurrent hypertension (HTN). Hypertensive left ventricular hypertrophy (LVH) does not exclude an underlying genetic aetiology.

Methods and results

This was a single-centre case–control study of 39 adults with pathologic HCM mutations, confirmed by genetic testing, compared to 39 age- and gender-matched patients with hypertensive LVH. The gene-positive HCM cohort was further stratified by the coexisting presence or absence of HTN. Clinical and echocardiographic characteristics were compared. Of 39 gene-positive HCM, 43.6% (17/39) had concurrent HTN. The gene-positive HCM cohort had larger left atrial (LA) area (22.1 cm2 vs. 18.9 cm2, P = 0.002), more diastolic predominant pulmonary vein flow (38.5% vs. 7.7%, P = 0.001), and more moderate diastolic dysfunction (33.3% vs. 12.8%, P = 0.032) when compared with the hypertensive LVH cohort. Greater left ventricular (LV) mass (277.7 g vs. 207.7 g, P = 0.025), increased frequency of severe LVH (58.8% vs. 27.3%, P = 0.047), and more abnormal global longitudinal strain (GLS) (−14.1% vs. −16.9%, P = 0.049) was observed in the gene-positive HCM cohort with concurrent HTN.

Conclusion

Gene-positive HCM, compared to hypertensive LVH, is characterized by more advanced diastolic dysfunction and larger LA size. Gene-positive HCM patients with concomitant HTN had greater LV mass, more severe LVH, and more abnormal GLS, suggesting HTN may negatively affect the progression of myocardial dysfunction in genetic HCM. LVH out-of-proportion to pressure burden in HTN patients should raise suspicion of underlying genetic HCM.
Segmentectomy versus lobectomy for solid predominant cN0 lung cancer: analysis using visual evaluation of positron emission tomography
Authors: Kagimoto Atsushi , Tsutani Yasuhiro , Mimae Takahiro , Miyata Yoshihiro , Okada Morihito
Published: October 2021

OBJECTIVES

Prognosis after segmentectomy for early-stage non-small cell lung cancer (NSCLC) with a high consolidation tumour ratio (CTR) and [18F]-fluoro-2-deoxy-d-glucose (FDG) accumulation on positron emission tomography/computed tomography is unclear.

METHODS

Participants of this study were 465 patients who underwent lobectomy or segmentectomy for clinical N0 NSCLC presenting solid component predominant tumour (CTR >50%) with a whole size ≤3 cm. Accumulations of FDG on positron emission tomography/computed tomography scans were scored according to the Deauville criteria, a 5-point visual evaluating method (Deauville score). The correlations between Deauville score, prognosis, and procedures were analysed.

RESULTS

Characteristics of pathological invasiveness, such as lymphatic invasion (P < 0.001), vascular invasion (P < 0.001) and pleural invasion (P < 0.001), and non-adenocarcinoma histologies (P < 0.001) were more common in patients with Deauville scores of 3–5. The cumulative incidence of recurrence (CIR) was higher in patients with Deauville scores of 3–5 (P < 0.001). The CIR after lobectomy and segmentectomy did not differ significantly among patients with Deauville scores of 1 or 2 (P = 0.598) or those with Deauville scores of 3–5 (P = 0.322). In the analysis of propensity score matched cohort, the CIR after lobectomy and segmentectomy did not differ significantly between patients with Deauville scores of 1 or 2 and Deauville scores of 3–5.

CONCLUSIONS

Segmentectomy may be feasible for NSCLC with high CTR (>50%) and accumulation of FDG. This finding should be confirmed in larger prospective studies.
The AfCFTA impact on agricultural and food trade: a value added perspective
Authors: Fusacchia Ilaria , Balié Jean , Salvatici Luca
Published: October 2021

The African Continental Free Trade Area agreement will create the largest single market in the world in terms of the number of countries and people. We analyse the effects of regional trade liberalisation on production fragmentation and networks using a global computable general equilibrium model adapted to take into account the value-added structure of international trade. This permits the analysis of the impact of trade policies in the presence of global upstream and downstream linkages through a counterfactual analysis. The analysis goes beyond previous studies by focusing on member countries’ agricultural and food integration in regional and global value chains through backward and forward linkages. Our simulation results suggest that the agreement could have a significant impact on trade patterns in terms of value-added structure and extra- or intra-regional destinations. The reduction in trade costs within the region has a higher incidence on agriculture and food backward intra-regional integration than on forward participation, but this pattern varies substantially across countries. We find that the continental agreement translates in more widely spread benefits across sectors if we consider the income generated within each sector (value added) rather than simply accounting for gross exports.
The association of general practitioners’ awareness of depression and anxiety with change in quality of life in heart failure patients: results of the prospective observational RECODE-HF cohort study
Authors: Eisele Marion , Rakebrandt Anja , Boczor Sigrid , Blozik Eva , Träder Jens-Martin , Störk Stefan , Herrmann-Lingen Christoph , Scherer Martin
Published: October 2021

Background

Depression and anxiety are more prevalent in patients with heart failure (HF) than in the general population and reduce quality of life (QoL); therefore, clinical guidelines recommend screening HF patients for depression/anxiety.

Objective

We investigated, whether the general practitioners’ (GPs) awareness of patients’ symptoms of depression and/or anxiety (psychosocial distress) was associated with a change in QoL.

Methods

In this prospective observational study, we recruited 3,129 primary care HF patients in Germany. Patients completed baseline and 12-month follow-up questionnaires. Their GPs were interviewed. We identified 666 patients with psychosocial distress and compared 2 groups by analysis of covariance: 235 patients with psychosocial distress whose GP was aware of the psychosocial distress and 431 patients with psychosocial distress whose GP was unaware of such distress. Primary outcome was the change in QoL, assessed by the EQ-5D visual analogue scale.

Results

Patients with psychosocial distress showed lower baseline QoL than those without (45.9 vs 64.1; P < 0.001). Within the patients with psychosocial distress, the GPs’ awareness of psychosocial distress was not associated with improvement of QoL (F = 1.285; P = 0.258) or remission of psychosocial distress (odds ratio = 0.887; P = 0.608).

Conclusion

We found no association between the GPs’ awareness of psychosocial distress and change in QoL. Although data for effective treatments of depression in HF are currently insufficient, psychosocial distress strongly impairs the QoL in HF patients. These findings might influence the development of clinical practice guidelines in HF.
Decrease of MYPT1 Is Critical for Impairment of NO-mediated Vasodilation in Mesenteric Artery of the Older Spontaneously Hypertensive Rats
Authors: Cui Yiqin , Yang Liju , Liu Xiaoqin , Che Chang , Cheng Jun , Li Pengyun , Wen Jing , Yang Yan
Published: October 2021

Nitric oxide (NO)-mediated vasodilatation is a fundamental response of vasculature, however, regulation of NO signaling pathway on resistance vessels in the older adult with hypertension is still unclear. The 16-week-spontaneously hypertensive rats (SHR), the 18-month-SHR (OldSHR), and the age-matched Wistar-Kyoto rats were used to study the changes of mesenteric resistance artery dilatation caused by sodium nitroprusside (SNP). After pre-vasoconstriction by norepinephrine (NE), the response of endothelium-denuded mesenteric artery ring to SNP was observed, and the changes in vascular response after pharmacological interventions of key nodes in the NO/sGC/cGMP/PKG1α signaling pathway were observed as well. RNA sequencing and functional enrichment analyses were used to provide information for conducting validation experiments. Vasodilation of NO in OldSHR was decreased, which significantly correlated with the reduction of PKG-mediated effect. Functional enrichment analysis of RNA sequencing showed that genes encoding important proteins such as sGC and MYPT1 (protein phosphatase 1 regulatory subunit 12A) were downregulated in OldSHR. Molecular biology validation results showed that mRNA expression of both α and β subunits of sGC were reduced, while mRNA and protein expression of PKG1α were reduced in OldSHR. More importantly, the expression of MYPT1 and pS668-MYPT1 was significantly reduced in OldSHR, even under the treatment of SNP. The experiment also revealed an enhanced cAMP system in vasodilation in hypertension, while this function was completely lost in the OldSHR. Therefore, an NO-mediated decrease in vascular smooth muscle relaxation was found in the OldSHR. The dysfunction in cGMP-PKG signaling, in particular, decreased pS668-MYPT1 was mechanistically involved.
Patterns of Prevalence of Multiple Sensory Impairments Among Community-dwelling Older Adults
Authors: Armstrong Nicole M , Wang Hang , E Jian-Yu , Lin Frank R , Abraham Alison G , Ramulu Pradeep , Resnick Susan M , Tian Qu , Simonsick Eleanor , Gross Alden L , Schrack Jennifer A , Ferrucci Luigi , Agrawal Yuri
Published: October 2021

Background

Much is known about individual sensory deficits among older adults, but there is a dearth of information about the prevalence of multiple concurrent sensory deficits in this population.

Methods

We evaluated the prevalence of individual and multiple sensory impairments at the most recent clinic visit among participants aged 24 years and older in the Baltimore Longitudinal Study of Aging (BLSA) (hearing, vision, olfaction, proprioception, and vestibular function) and Atherosclerosis Risk in Communities Study (ARIC) (hearing, vision, olfaction). We compared observed prevalence of multiple sensory impairments with expected prevalence based on compounded probabilities of multiple impairments using Fisher Exact Tests. Also, we evaluated the comparability of different measures used between these two studies.

Results

In both studies, the prevalence of each individual sensory impairment was common (>10%), and higher with older age, and the most common pattern of co-occurring sensory impairments was hearing and visual impairments (17.4% [BLSA]; 50.2% [ARIC]). In BLSA, the pattern that differed the most between observed and expected prevalence was combined hearing, vision, and olfactory impairments (observed 5.2% vs 1.4% expected, p = .01). In ARIC, this difference was much smaller (observed 8.1% vs 7.2% expected, p = .49).

Conclusions

Although concurrent hearing and vision impairments were the most common co-occurring deficits, combined hearing, vision, and olfactory impairments are most likely to co-occur above chance, especially at older ages.