bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for the earliest structural use of wood at least 476,000 years ago
Authors: Barham L. , Duller G. A. T. , Candy I. , Scott C. , Cartwright C. R. , Peterson J. R. , Kabukcu C. , Chapot M. S. , Melia F. , Rots V. , George N. , Taipale N. , Gethin P. , Nkombwe P.
Published: September 2023

Wood artefacts rarely survive from the Early Stone Age since they require exceptional conditions for preservation; consequently, we have limited information about when and how hominins used this basic raw material1. We report here on the earliest evidence for structural use of wood in the archaeological record. Waterlogged deposits at the archaeological site of Kalambo Falls, Zambia, dated by luminescence to at least 476 ± 23 kyr ago (ka), preserved two interlocking logs joined transversely by an intentionally cut notch. This construction has no known parallels in the African or Eurasian Palaeolithic. The earliest known wood artefact is a fragment of polished plank from the Acheulean site of Gesher Benot Ya’aqov, Israel, more than 780 ka (refs. 2,3). Wooden tools for foraging and hunting appear 400 ka in Europe4–8, China9 and possibly Africa10. At Kalambo we also recovered four wood tools from 390 ka to 324 ka, including a wedge, digging stick, cut log and notched branch. The finds show an unexpected early diversity of forms and the capacity to shape tree trunks into large combined structures. These new data not only extend the age range of woodworking in Africa but expand our understanding of the technical cognition of early hominins11, forcing re-examination of the use of trees in the history of technology12,13.
Transcriptional linkage analysis with in vivo AAV-Perturb-seq
Authors: Santinha Antonio J. , Klingler Esther , Kuhn Maria , Farouni Rick , Lagler Sandra , Kalamakis Georgios , Lischetti Ulrike , Jabaudon Denis , Platt Randall J.
Published: September 2023

The ever-growing compendium of genetic variants associated with human pathologies demands new methods to study genotype–phenotype relationships in complex tissues in a high-throughput manner1,2. Here we introduce adeno-associated virus (AAV)-mediated direct in vivo single-cell CRISPR screening, termed AAV-Perturb-seq, a tuneable and broadly applicable method for transcriptional linkage analysis as well as high-throughput and high-resolution phenotyping of genetic perturbations in vivo. We applied AAV-Perturb-seq using gene editing and transcriptional inhibition to systematically dissect the phenotypic landscape underlying 22q11.2 deletion syndrome3,4 genes in the adult mouse brain prefrontal cortex. We identified three 22q11.2-linked genes involved in known and previously undescribed pathways orchestrating neuronal functions in vivo that explain approximately 40% of the transcriptional changes observed in a 22q11.2-deletion mouse model. Our findings suggest that the 22q11.2-deletion syndrome transcriptional phenotype found in mature neurons may in part be due to the broad dysregulation of a class of genes associated with disease susceptibility that are important for dysfunctional RNA processing and synaptic function. Our study establishes a flexible and scalable direct in vivo method to facilitate causal understanding of biological and disease mechanisms with potential applications to identify genetic interventions and therapeutic targets for treating disease.
Cancer-specific association between Tau (MAPT) and cellular pathways, clinical outcome, and drug response
Authors: Callari Maurizio , Sola Martina , Magrin Claudia , Rinaldi Andrea , Bolis Marco , Paganetti Paolo , Colnaghi Luca , Papin Stéphanie
Published: September 2023

Tau (MAPT) is a microtubule-associated protein causing common neurodegenerative diseases or rare inherited frontotemporal lobar degenerations. Emerging evidence for non-canonical functions of Tau in DNA repair and P53 regulation suggests its involvement in cancer. To bring new evidence for a relevant role of Tau in cancer, we carried out an in-silico pan-cancer analysis of MAPT transcriptomic profile in over 10000 clinical samples from 32 cancer types and over 1300 pre-clinical samples from 28 cancer types provided by the TCGA and the DEPMAP datasets respectively. MAPT expression associated with key cancer hallmarks including inflammation, proliferation, and epithelial to mesenchymal transition, showing cancer-specific patterns. In some cancer types, MAPT functional networks were affected by P53 mutational status. We identified new associations of MAPT with clinical outcomes and drug response in a context-specific manner. Overall, our findings indicate that the MAPT gene is a potential major player in multiple types of cancer. Importantly, the impact of Tau on cancer seems to be heavily influenced by the specific cellular environment.
On the local warming potential of urban rooftop photovoltaic solar panels in cities
Authors: Khan Ansar , Santamouris Mattheos
Published: September 2023

Understanding and evaluating the implications of photovoltaic solar panels (PVSPs) deployment on urban settings, as well as the pessimistic effects of densely populated areas on PVSPs efficiency, is becoming incredibly valuable. Thus, the deployment of low-efficiency, low-cost, and widely available PVSPs may diminish total solar reflectance, raising the risks of PVSPs-based urban heating, particularly during the summertime heatwaves. This study employs and assesses physical parameterizations that account for the impact of PVSPs on Sydney’s urban environment in the context of the mesoscale model weather research and forecasting (WRF). To account for the impacts of PVSPs, the parameterization presented in this paper assumes that PVSP arrays are parallel, detachable from roofs, and consist of a single layer. Results showed that increasing PVSPs can raise peak summer ambient temperatures by up to 1.4 °C and surface temperatures by up to 2.3°C at city-scale. Temperature variability was found between the city’s eastern and western parts due to the presence of PVSPs. In addition, local warming effects of PVSP were observed at urban district-scale as well. The large-scale deployment of PVSPs at local district-scale of the Sydney during a typical hot day caused air temperature to rise by 1.5 °C during the daytime and decrease by 2.7 °C at nighttime. The patterns of the city’s ambient temperature distribution were found to be strongly dependent on synoptic meteorological conditions and advection flow strength. The maximum increases in sensible heat flux and latent heat flux were 245.5 Wm−2 and 11.5 Wm−2, respectively. Wind speed may be raised by up to 1.2 ms−2 due to regional low effect over city domain. As a result, large-scale deployment of PVSPs promotes advective flow between the city and its environs. Modification of the PVSPs in Sydney results in an increase in planetary boundary layer (PBL) heights of up to 537.9 m above the city and may lower pollutant concentrations at ground level. The advent of sea breeze in the city’s eastern parts, which reduces the temperature of the coastal zone, along with inland westerly winds, which heat the city’s western zones, lessened the intensity of the urban heat island (UHI) phenomenon induced by PVSPs warming. The findings of this study can be used to help policymakers make informed decisions about the use of PVSPs systems. PVSPs with a high solar reflectance in wavelengths that do not convert solar energy to electricity can be considered as an alternative solution to reduce local warming in urban environments.
Conceptual relatedness promotes memory generalization at the cost of detailed recollection
Authors: Melega Greta , Sheldon Signy
Published: September 2023

An adaptive memory system is one that allows us to both retrieve detailed memories as well as generalize knowledge about our past, the latter termed memory generalization and is useful for making inferences about new situations. Research has indicated that memory generalization relies on forming knowledge structures by integrating experiences with shared encountered elements. Whether memory generalization occurs more readily when  experiences also have elements that share established (conceptual) information is less clear. It is also unclear if engaging in memory generalization during learning comes at the cost of retrieving detailed memories, the other function of episodic memory. To address these two knowledge gaps, we paired a modified version of the acquired equivalence task with a recognition memory test. Across three experiments, participants first learned a series of overlapping object-scene pairs (A–X, B–X and A–Y) in which half of the overlapping pairs contained conceptually-related objects (e.g., A—pencil; B—scissors; conceptual condition) and the other half contained unrelated objects (neutral condition). Participants ability to generalize to new overlapping object-scene pairs (B–Y) as well as not-learned but semantically-related objects was measured. Finally, participants completed a recognition memory test that included the encoded objects, perceptually similar lures or new foil objects. Across all experiments, we found higher rates of generalization but reduced detailed memory (indexed by increased false alarms to lure objects) for information learned in the conceptual than neutral condition. These results suggest the presence of conceptual knowledge biases an individual towards a generalization function of memory, which comes at the expense of detailed recollection.
Conservative versus early surgical treatment in the management of pyogenic spondylodiscitis: a systematic review and meta-analysis
Authors: Thavarajasingam Santhosh G. , Vemulapalli Kalyan V. , Vishnu K. Sajeenth , Ponniah Hariharan Subbiah , Vogel Alexander Sanchez-Maroto , Vardanyan Robert , Neuhoff Jonathan , Kramer Andreas , Shiban Ehab , Ringel Florian , Demetriades Andreas K. , Davies Benjamin M.
Published: September 2023

Spondylodiscitis is the commonest spine infection, and pyogenic spondylodiscitis is the most common subtype. Whilst antibiotic therapy is the mainstay of treatment, some advocate that early surgery can improve mortality, relapse rates, and length of stay. Given that the condition carries a high mortality rate of up to 20%, the most effective treatment must be identified. We aimed to compare the mortality, relapse rate, and length of hospital stay of conservative versus early surgical treatment of pyogenic spondylodiscitis. All major databases were searched for original studies, which were evaluated using a qualitative synthesis, meta-analyses, influence, and regression analyses. The meta-analysis, with an overall pooled sample size of 10,954 patients from 21 studies, found that the pooled mortality among the early surgery patient subgroup was 8% versus 13% for patients treated conservatively. The mean proportion of relapse/failure among the early surgery subgroup was 15% versus 21% for the conservative treatment subgroup. Further, it concluded that early surgical treatment, when compared to conservative management, is associated with a 40% and 39% risk reduction in relapse/failure rate and mortality rate, respectively, and a 7.75 days per patient reduction in length of hospital stay (p < 0.01). The meta-analysis demonstrated that early surgical intervention consistently significantly outperforms conservative management in relapse/failure and mortality rates, and length of stay, in patients with pyogenic spondylodiscitis.
Ecological, morpho-agronomical, and bromatological assessment of sorghum ecotypes in Northern Morocco
Authors: Boukrouh S. , Noutfia A. , Moula N. , Avril C. , Louvieaux J. , Hornick J.L. , Cabaraux J.F. , Chentouf M.
Published: September 2023

Sorghum Bicolor is a cereal used for grains as feed and food, mainly cultivated in dry areas. To study the possibilities of increasing its cultivation for feed purposes, ecological, morpho-agronomical, and bromatological characterization of some local ecotypes was conducted as the first steps toward selecting better cultivars. Indeed, twenty-one ecotypes were collected from farms in Northern Morocco in 2018. The edapho-climatic parameters of the collection sites were evaluated. The ecotypes were cultivated in 2019 in an experimental field with a randomized complete block design with three replicates. At the maturity stage, plants were evaluated for agro-morphological parameters, and grains and straw (leaves and stems) were harvested and analyzed. The results indicated significant variations between ecotypes for almost all parameters and an interesting grain yield of 3.5 T/ha with a 176% yield variation. The nutritive value of grains was interesting compared to straw, especially for mean protein contents (10.5% DM) and organic matter digestibility (81.4%). The calculated genetic parameters emphasized the possibility of selecting highly productive and nutritive cultivars. Multivariate analysis clustered the ecotypes into five groups based on agro-morphological, bromatological, and antioxidant activity parameters; the third group was characterized by high grain-yielding ecotypes, and the fifth one by high nutritive ecotypes. The E21 ecotype, belonging to this last group, was a promising selection candidate as it combines both. No significant correlation link between agro-morphological and bromatological traits of grains and geographical distances was discerned. Sorghum bicolor could thus be improved only according to the researched agro-morphological and bromatological traits.
Design, molecular modelling and synthesis of novel benzothiazole derivatives as BCL-2 inhibitors
Authors: Ismail Hoda S. , Khalil Amira , Taha Rabah A. , Lasheen Deena S. , Abou El Ella Dalal A.
Published: September 2023

Apoptosis plays a crucial role in cancer pathogenesis and drug resistance. BCL-2 family of enzymes is considered as one of the key enzymes which is involved in apoptosis. When there is disruption in the balance between anti-apoptotic and pro-apoptotic members of the BCL-2 family apoptosis is dysregulated in the affected cells. Herein, 33 novel benzothiazole-based molecules 7a-i, 8a-f, 9a-b, 12a-e, 13a-d, 14a,b, and 17a-j were designed, synthesized and tested for their BCL-2 inhibitory activity. Scaffold hopping strategy was applied in designing of the target compounds. Compounds 13c and 13d showed the highest activity with IC50 values equal to 0.471 and 0.363 µM, respectively. Molecular docking studies of the synthesized compounds showed comparable binding interactions with the lead compound. Structure activity relationship study was performed to show the effects of structural modifications on the inhibitory activities on BCL-2.
Fast dynamics and high effective dimensionality of liquid fluidity
Authors: Cockrell C. , Dicks O. , Todorov I. T. , Elena A. M. , Trachenko K.
Published: September 2023

Fluidity, the ability of liquids to flow, is the key property distinguishing liquids from solids. This fluidity is set by the mobile transit atoms moving from one quasi-equilibrium point to the next. The nature of this transit motion is unknown. Here, we show that flow-enabling transits form a dynamically distinct sub-ensemble where atoms move on average faster than the overall system, with a manifestly non-Maxwellian velocity distribution. This is in contrast to solids and gases where no distinction of different ensembles can be made and where the distribution is always Maxwellian. The non-Maxwellian distribution is described by an exponent $$\alpha$$
α
corresponding to high dimensionality of space. This is generally similar to extra synthetic dimensions in topological quantum matter, albeit higher dimensionality in liquids is not integer but is fractional. The dimensionality is close to 4 at melting and exceeds 4 at high temperature. $$\alpha$$
α
has a maximum as a function of temperature and pressure in liquid and supercritical states, returning to its Maxwell value in the solid and gas states.
Research on charge induction law and application of coal samples with different fissures
Authors: Wang Gang , Gao Siqi , Wang Aiwen , Dai Lianpeng , Shi Tianwei , Xu Zengjun
Published: September 2023

Indoor testing are performed to explore the charge induction law during the uniaxial compression fracture process of coal samples, and the charge time and frequency domain signals of coal samples with different primary fissures are analyzed in the paper. On-site monitoring of charge in different fissures distribution areas of underground coal tunnels, and the charge signals of different drillingdepths in coal seams are analyzed. The results show that the uniaxial compressive strength and elastic modulus of multi-fissured coal samples are less than those of less fissured coal samples, and the Poisson’s ratio is greater than those of less fissured coal samples. The charge induction signal intensity during the fracture process of multi-fissured coal samples is relatively low, but it is concentrated at the low frequency of 0–50 Hz in the compacting elasticity stage. The charge signal intensity during the fracture process of coal samples with less fissure is relatively high, and the charge frequency during the reinforcement damage stage is concentrated at a low frequency of 0–50 Hz. Therefore, the sudden appearance of low-frequency charge signals is more suitable as effective precursor information for the instability and failure of less fissured coal bodies. The average charge intensity is small in the multi-fissured area with a drilling depth of 1–4 m in the coal seam, and the average charge intensity of the coal body with less fissures is larger in the 5–12 m region. The on-site charge monitoring results have good consistency with the indoor test results. This study has guiding significance in setting up a charge monitoring warning index of instability failure in different coal body fissures regions.
Affine transformations accelerate the training of physics-informed neural networks of a one-dimensional consolidation problem
Authors: Mandl Luis , Mielke André , Seyedpour Seyed Morteza , Ricken Tim
Published: September 2023

Physics-informed neural networks (PINNs) leverage data and knowledge about a problem. They provide a nonnumerical pathway to solving partial differential equations by expressing the field solution as an artificial neural network. This approach has been applied successfully to various types of differential equations. A major area of research on PINNs is the application to coupled partial differential equations in particular, and a general breakthrough is still lacking. In coupled equations, the optimization operates in a critical conflict between boundary conditions and the underlying equations, which often requires either many iterations or complex schemes to avoid trivial solutions and to achieve convergence. We provide empirical evidence for the mitigation of bad initial conditioning in PINNs for solving one-dimensional consolidation problems of porous media through the introduction of affine transformations after the classical output layer of artificial neural network architectures, effectively accelerating the training process. These affine physics-informed neural networks (AfPINNs) then produce nontrivial and accurate field solutions even in parameter spaces with diverging orders of magnitude. On average, AfPINNs show the ability to improve the $${\mathscr {L}}_2$$

L
2

relative error by $$64.84\%$$

64.84
%

after 25,000 epochs for a one-dimensional consolidation problem based on Biot’s theory, and an average improvement by $$58.80\%$$

58.80
%

with a transfer approach to the theory of porous media.
Convolutional neural networks for mode on-demand high finesse optical resonator design
Authors: Karpov Denis V. , Kurdiumov Sergei , Horak Peter
Published: September 2023

We demonstrate the use of machine learning through convolutional neural networks to solve inverse design problems of optical resonator engineering. The neural network finds a harmonic modulation of a spherical mirror to generate a resonator mode with a given target topology (“mode on-demand”). The procedure allows us to optimize the shape of mirrors to achieve a significantly enhanced coupling strength and cooperativity between a resonator photon and a quantum emitter located at the center of the resonator. In a second example, a double-peak mode is designed which would enhance the interaction between two quantum emitters, e.g., for quantum information processing.
Association between lactate/albumin ratio and all-cause mortality in critical patients with acute myocardial infarction
Authors: Wang Danni , Luo Chaodi , Li Qian , Zheng Tingting , Gao Pengjie , Wang Boxiang , Duan Zhenzhen
Published: September 2023

It has been demonstrated that lactate/albumin (L/A) ratio is substantially relevant to the prognosis of sepsis, septic shock, and heart failure. However, there is still debate regarding the connection between the L/A ratio and severe acute myocardial infarction (AMI). The aim of this study is to determine the prognostic role of L/A ratio in patients with severe AMI. Our retrospective study extracted data from the Medical Information Mart for Intensive Care III (MIMIC-III) database, included 1,134 patients diagnosed with AMI. Based on the tertiles of L/A ratio, the patients were divided into three groups: Tertile1 (T1) group (L/A ratio<0.4063, n=379), Tertile2 (T2) group (0.4063≤L/A ratio≤0.6667, n =379), and Tertile3 (T3) group (L/A ratio>0.6667, n =376). Uni- and multivariate COX regression model were used to analyze the relationship between L/A ratio and 14-day, 28-day and 90-day all-cause mortality. Meanwhile, the restricted cubic spline (RCS) model was used to evaluate the effect of L/A ratio as a continuous variable. Higher mortality was observed in AMI patients with higher L/A ratio. Multivariate Cox proportional risk model validated the independent association of L/A ratio with 14-day all-cause mortality [hazard ratio (HR) 1.813, 95% confidence interval (CI) 1.041-3.156 (T3 vs T1 group)], 28-day all-cause mortality [HR 1.725, 95% CI 1.035-2.874 (T2 vs T1 group), HR 1.991, 95% CI 1.214-3.266 (T3 vs T1 group)], as well as 90-day all-cause mortality [HR 1.934, 95% CI 1.176-3.183 (T2 vs T1 group), HR 2.307, 95% CI 1.426-3.733 (T3 vs T1 group)]. There was a consistent trend in subgroup analysis. The Kaplan-Meier (K-M) survival curves indicated that patients with L/A ratio>0.6667 had the highest mortality. Even after adjusting the confounding factors, RCS curves revealed a nearly linearity between L/A ratio and 14-day, 28-day and 90-day all-cause mortality. Meanwhile, the areas under the receiver operating characteristic (ROC) curve (AUC) of 14-day, 28-day and 90-day all-cause mortality were 0.730, 0.725 and 0.730, respectively. L/A ratio was significantly associated with 14-day, 28-day and 90-day all-cause mortality in critical patients with AMI. Higher L/A ratio will be considered an independent risk factor for higher mortality in AMI patients.
Discordance diagnosis between B-mode ultrasonography and MRI proton density fat fraction for fatty liver
Authors: Lee Chul-min , Kim Mimi , Kang Bo-Kyeong , Jun Dae Won , Yoon Eileen L.
Published: September 2023

We aimed to evaluate the frequency and causes of discordant results in fatty liver (FL) diagnosis between B-mode ultrasonography (B-USG) and magnetic resonance imaging proton density fat fraction (MRI-PDFF). We analyzed patients who underwent both B-USG and MRI-PDFF within a 6-month interval. We made a confusion matrix for FL diagnosis between B-USG and MRI-PDFF and identified four discordant groups as follows: (1) the “UFL-MnFL-wo” group [B-USG FL–MRI-PDFF no FL without chronic liver disease (CLD) or liver cirrhosis (LC)]; (2) the “UFL-MnFL-w” group (B-USG FL–MRI-PDFF no FL with CLD or LC); (3) the “UnFL-MFL-wo” group (B-USG no FL–MRI-PDFF FL without CLD or LC); and (4) the “UnFL-MFL-w” group (B-USG no FL–MRI-PDFF FL with CLD or LC). We compared the “UFL-MnFL-wo” group with the control group in terms of various parameters. We found 201 patients (201/1514, 13.3%) with discordant results for FL diagnosis between B-USG and MRI-PDFF. The “UFL-MnFL-wo” group accounted for the largest portion at 6.8% (103/1514), followed by the “UFL-MnFL-w” group (79/1514, 5.2%) and the “UnFL-MFL-w” group (16/1514, 1.1%). The mean and right PDFF values, body mass index, and abdominal wall thickness were significantly higher in the “UFL-MnFL-wo” group than in the control group (p ≤ 0.001). The frequency of discordant results in the diagnosis of FL between B-USG and MRI-PDFF could be identified. The causes of discordant results were that B-USG was fairly accurate in diagnosing FL disease and that accompanying CLD or LC hindered the evaluation of FL.
Analyzing the horizontal orientation of the crustal stress adjacent to plate boundaries
Authors: Stephan Tobias , Enkelmann Eva , Kroner Uwe
Published: September 2023

The spatial analysis of horizontal stress orientation is important to study stress sources and understand tectonics and the deformation of the lithosphere. Additional to the stress sources, the geometry of stress fields depends on the underlying coordinate reference system, which causes spatial distortions that bias the analysis and interpretation of stresses. The bias can be avoided when the stress field is decomposed and transformed into the reference frame of its first-order stress source. We present a modified and extended theory based on the empirical link between the orientation of first-order stresses and the trajectories of lateral plate boundary forces. This link is applied to analyze the orientation of horizontal stresses, their patterns, and tectonic structures from the perspective of their first-order source or cause. By using only parameters for the relative motion between two neighboring plates, we model the first-order orientation of the maximum horizontal stress that statistically fits the orientation of $$\ge$$
≥
80% of the global stress data adjacent to plate boundaries. Considerable deviations of the observed stress from the predicted first-order stress direction can reveal the geometry of second-order stresses and confine areas where other stress sources dominate. The model’s simple assumptions, independence from the sample size, potential application to regional to global scale analysis, and compatibility with other spatial interpolation algorithms make it a powerful method for analyzing stress fields. For immediate use, the presented method is implemented in the free and open-source software package , which is written in the computer language R.
Bonitation assessment of intensively used football turf depending on the date and area of observation
Authors: Wolski Karol , Sobol Łukasz , Bujak Henryk
Published: September 2023

This article aimed to evaluate the visual and functional characteristics of intensively used football turf over 10 years, depending on the different areas of the game. The research was conducted on the football turf of the AZS Environmental Club in Wrocław (N: 51° 7′ 31′′ E:17° 4′ 14′′). High variability of the evaluated parameters was observed regarding seasonality, year of observation, and the area of play. It has been shown that the goal area and penalty box areas have the lowest functional value, which are vital areas of the game from the point of view of gaining an advantage in the game. Also, these places are more susceptible to creating sites without plants (requiring additional overseeding) due to the potential of hollowing and goalkeeper interventions ending with the body landing on the ground. The middle area was characterized by the highest overall aspect, color, and turf density values. In the vast majority of cases, there was a downward trend in the turfs’ functional value with the turf’s age, which is an essential finding in the context of the use of intensively used, athletic natural grass surfaces.
Peripheral nerve stimulation for the treatment of chronic knee pain
Authors: Früh Anton , Sargut Tarik Alp , Hussein Abdelhalim , Muskala Bartolomäus , Kuckuck Anja , Brüßeler Melanie , Vajkoczy Peter , Bayerl Simon
Published: September 2023

The average age of our population is increasing, resulting in a high incidence of chronic degenerative knee pathologies. Several treatment options, including surgical procedures are available to help mitigate these pathologies. However, the percentage of subjects with chronic post-surgical knee pain is still estimated at 16–20%. Neuromodulation techniques such as spinal cord stimulation and dorsal root ganglion stimulation (DRGS) are treatment options for subjects with chronic knee pain. The evidence for peripheral nerve stimulation (PNS) is minimal due to a limited number of neuromodulation systems capable of targeting the distal part of the lower limbs. This study aimed to investigate the safety and efficacy externally powered PNS systems for the treatment of chronic intractable knee pain targeting the saphenous nerve. Patients suffering from chronic intractable post-surgical knee pain received landmark-guided peripheral nerve stimulation of the branches of the saphenous nerve. All implants were performed with an externally powered PNS system to avoid lead migration as a result of cross-joint lead positions tunneling towards an Implantable Pulse Generator to the trunk. Data were collected retrospectively. Subject-reported outcome was measured via numerical rating scale values on a 10-point scale measuring pain intensity at rest and in motion. Additional data were collected for the subjects treated at the Charité location, including quality of life with the SF-36 form, quality of sleep with the Pittsburgh Sleep Quality Index and mood states with the short form of the General Depression Scale. Thirty-three patients received direct to permanent implant, landmark-guided peripheral nerve stimulation of the saphenous nerve branches. Six (18.2%) subjects reported non-sufficient initial benefit from the therapy and were explanted. Two subjects were explanted due to wound infections. The total study population reported included 25 patients. These subjects reported significant improvements related to pain, quality of life, mood quality, and quality of sleep. Additionally, subjects were able to reduce their opioid medication significantly after PNS therapy. Externally powered PNS at the saphenous nerve branches is a straightforward, selective and safe technique for patients with chronic knee pain. The landmark-guided implantation technique is less invasive than classical neuromodulation techniques such as spinal cord or DRGS and complication rates remain low. Short-term results are promising and show considerable reductions in pain scores and opioid intake. Long-term results are pending.
Interfacial phenomenon and Marangoni convection of Fe–C melt on coke substrate under in situ observation
Authors: Gao Lihua , Huang Yibin , Zhan Wenlong , Wang Chuan , He Zhijun , Pang Qinghai , Zhang Junhong
Published: September 2023

The interfacial phenomenon between liqiuid iron and coke is important for determining the melting efficiency in the blast furnace iron-making process. In this study, the interaction observed in the case of the iron-carbon (Fe–C) melt on coke substrate was investigated using a high-temperature vacuum wettability test equipment. The Fe–C melt did not wet and spread on the coke substrate with different graphitization degrees (r0) at a high temperature of 1450 °C. The contact angles changed from 124.5° to 105.3°, and the r0 increased from 9.30 to 50.00%, thus indicating a nonwetting state. The deepening of graphitization decreased the contact angle. Thereby, increasing the contact area between liquid iron and the carbonaceous material, which facilitated carbon dissolution. The irregular movements of Fe–C melt were observed in situ during the wetting process. The horizontal force of the droplet caused by interfacial tension and the contact angle; the Marangoni convection owing to the gradient of carbon concentration; and the impulse force caused by the generation, aggregation, and release of SiO bubbles at the interface were attributed to the driving force.
Galantamine improves glycemic control and diabetic nephropathy in Leprdb/db mice
Authors: Meng Qinghe , Ma Julia , Suo Liye , Pruekprasert Napat , Chakrapani Prithi , Cooney Robert N.
Published: September 2023

Galantamine, a centrally acting acetylcholinesterase inhibitor, has been shown to attenuate inflammation and insulin resistance in patients with metabolic syndrome. We investigated the effects of galantamine on glycemic control and development of diabetic nephropathy (DN) in Leprdb/db mice. Galantamine significantly reduced food intake, body weight, blood glucose and HbA1c levels. Insulin resistance (HOMA-IR, QUICKI), HOMA-β and elevations in plasma inflammatory cytokine levels (TNF-α, IL-6 and HMGB-1) were all attenuated by galantamine. Galantamine also ameliorated diabetes-induced kidney injury as evidenced by improvements in renal function (BUN, creatinine, albuminuria), histologic injury and apoptosis. Improved glycemic control and nephropathy were associated with increased circulating GLP-1, decreased renal P-38 MAPK and caspase-1 activation and reduced SGLT-2 expression. These findings provide insights into the mechanisms by which galantamine improves glycemic control and attenuates DN in the Leprdb/db mouse model.
Synthesis, spectroscopic, DFT calculations, biological activity, SAR, and molecular docking studies of novel bioactive pyridine derivatives
Authors: Anwer Kurls E. , Hamza Zeinab K. , Ramadan Ramadan M.
Published: September 2023

Enaminonitrile pyridine derivative was used as a precursor for preparation of fourteen heterocyclic compounds using both conventional thermal and microwave techniques. Diverse organic reagents, such as chloroacetyl chloride, acetic anhydride, chloroacetic acid, carbon disulfide,p-toluene sulfonyl chloride, maleic anhydride, phthalic anhydride, were used. The chemical formulae and structures of isolated derivatives were obtained using different analytical and spectroscopic techniques such as IR,1H-,13C-NMR as well as mass spectrometry. The spectroscopic analyses revealed diverse structure arrangements for the products. Molecular structure optimization of certain compounds were performed by the density functional theory (DFT/B3LYP) method and the basis set 6–31 G with double zeta plus polarization (d,p). The antimicrobial inhibition and the antioxidant activity of the reported compounds were screened. Compounds5,6,11and13exhibited the highest antibacterial inhibition, while compound8gave the highest scavenging activity (IC50 43.39 µg/ml) against the DPPH radical. Structure–activity relationship of the reported compounds were correlated with the data of antibacterial and the antioxidant activity. The global reactivity descriptors were also correlated with the biological properties of compounds. The molecular docking studies of reported compounds were investigated, and the analysis showed that the docked compounds have highly negative values for the functional binding scores. The binding interaction was found to be correlated with the substituent fragments of the compounds.
Generation of a familial hypercholesterolemia model in non-human primate
Authors: Sato Akira , Tsukiyama Tomoyuki , Komeno Masahiro , Iwatani Chizuru , Tsuchiya Hideaki , Kawamoto Ikuo , Murase Mitsuru , Nakagawa Takahiro , Itagaki Iori , Seita Yasunari , Matsumoto Shoma , Nakaya Masataka , Shimizu Akio , Yamada Atsushi , Ema Masatsugu , Ogita Hisakazu
Published: September 2023

Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is associated with a high plasma level of low-density lipoprotein (LDL) cholesterol, leading to an increased risk of cardiovascular diseases. To develop basic and translational research on FH, we here generated an FH model in a non-human primate (cynomolgus monkeys) by deleting the LDL receptor (LDLR) gene using the genome editing technique. Six LDLR knockout (KO) monkeys were produced, all of which were confirmed to have mutations in the LDLR gene by sequence analysis. The levels of plasma cholesterol and triglyceride were quite high in the monkeys, and were similar to those in FH patients with homozygous mutations in the LDLR gene. In addition, periocular xanthoma was observed only 1 year after birth. Lipoprotein profile analysis showed that the plasma very low-density lipoprotein and LDL were elevated, while the plasma high density lipoprotein was decreased in LDLR KO monkeys. The LDLR KO monkeys were also strongly resistant to medications for hypercholesterolemia. Taken together, we successfully generated a non-human primate model of hypercholesterolemia in which the phenotype is similar to that of homozygous FH patients.
Risk factors for liner wear and head migration in total hip arthroplasty: a systematic review
Authors: Migliorini Filippo , Maffulli Nicola , Pilone Marco , Bell Andreas , Hildebrand Frank , Konrads Christian
Published: September 2023

Total hip arthroplasty (THA) is a successful orthopaedic surgical procedure, and its longevity depends on bearing components and implant fixation. Optimizing polyethylene and ceramics has led to improved wear parameters and contributed to improved long-term outcomes. The present systematic review investigated whether time span from implantation, patient characteristics and performance status exert an influence on liner wear and head migration in THA. This study was conducted in conformity to the 2020 PRISMA guidelines. All the clinical investigations which reported quantitative data on the amount of liner wear and head migration in THA were considered. Only studies which reported quantitative data at least on one of the following patient characteristics were suitable: mean age, mean BMI (kg/m2), sex, side, time span between the index THA and the last follow-up (months) were eligible. A multiple linear model regression analysis was employed to verify the association between patient characteristics and the amount of liner wear and/or head migration. The Pearson Product-Moment Correlation Coefficient was used to assess the association between variables. Data from 12,629 patients were considered. The mean length of the follow-up was 90.5 ± 50.9 months. The mean age of patients at surgery was 58.4 ± 9.4 years, and the mean BMI was 27.2 ± 2.5 kg/m2. 57% (7199 of 12,629 patients) were women, and in 44% (5557 of 12,629 patients) THAs were performed on the left. The mean pre-operative Harris hip score was 46.5 ± 6.0 points. There was evidence of a moderate positive association between the amount of liner wear and the time elapsed between the index surgery to the follow-up (P = 0.02). There was evidence of a moderate positive association between the amount of head migration and the time elapsed between the index surgery to the follow-up (P = 0.01). No further statistically significant association was found. The time elapsed between the index surgery to the follow-up was the most important factor which influence the head migration and liner wear in THA. Patients’ characteristics and preoperative physical activity did not influence the amount of head migration and liner wear.
Trends and practices following the 2016 hydroxychloroquine screening guidelines
Authors: Kalaw Fritz Gerald P. , Arnett Justin , Baxter Sally L. , Walker Evan , Pedersen Brian , Borooah Shyamanga
Published: September 2023

This study aimed to understand the profile of hydroxychloroquine-treated patients, referral patterns, and dosing and to assess the adherence of eye care providers to the latest 2016 screening guidelines provided by the American Academy of Ophthalmology. Patients were identified using electronic health records (EHR) taking hydroxychloroquine and were seen by optometrists, retinal specialists, and non-retinal ophthalmologists. Review of EHR data includes demographic characteristics, indications, and dosing profile of hydroxychloroquine use, eye care provider managing the patient, and imaging modalities performed. A total of 166 patients were included in the study. The most common indications for screening were systemic lupus erythematosus and discoid lupus (52.4%) followed by rheumatoid arthritis (18.7%) and Sjögren’s syndrome (9.6%). Ninety-two (55.4%) patients were on a higher-than-recommended dose of > 5 mg/kg/day. Patients who weighed less (mean 63.9 kg) were taking a higher-than-recommended dose (vs. 81.5 kg, p < 0.001). Although retinal specialists adhered best to the use of all three recommended imaging modalities, visual field testing was done appropriately for only 8.3% of Asian and 71.1% of non-Asian patients. In conclusion, there is substantial variability in screening by ophthalmic providers and prescribing practices compared with the current recommendations. In particular, there is a marked deficiency in correct visual field testing in Asian patients. These findings are important to highlight potential interventions to improve screening for hydroxychloroquine toxicity.
CPD-CCNN: classification of pepper disease using a concatenation of convolutional neural network models
Authors: Bezabh Yohannes Agegnehu , Salau Ayodeji Olalekan , Abuhayi Biniyam Mulugeta , Mussa Abdela Ahmed , Ayalew Aleka Melese
Published: September 2023

Agricultural products are vital to the sustainability of the economies of developing countries. Most developing countries’ economies such as Ethiopia heavily rely on agriculture. On a global scale, the pepper crop is one of the most important agricultural products in terms of human food security. However, it is susceptible to a variety of diseases which include blight leaf disease, gray leaf spot, common rust, fruit rot disease, powdery mildew symptoms on pepper leaf, and other related diseases that are all common today. Currently, more than 34 different pepper diseases have been discovered, resulting in a 33% average yield loss in pepper cultivation. Conventionally, farmers detect the disease using visual observation but this has its own demerits as it is usually not accurate and usually time consuming. In the past, a number of researchers have presented various methods for classifying pepper plant disease, especially using image processing and deep learning techniques. However, earlier studies have shown that binary classification requires improvement as some classes were more challenging to identify than others. In this study, we propose a concatenated neural network of the extracted features of VGG16 and AlexNet networks to develop a pepper disease classification model using fully connected layers. The development of the proposed concatenated CNN model includes steps such as dataset collection, image preprocessing, noise removal, segmentation, feature extraction, and classification. Finally, the proposed concatenated CNN model was evaluated, providing a training classification accuracy of 100%, validation accuracy of 97.29%, and testing accuracy of 95.82%. In general, it can be concluded from the findings of the study that the proposed concatenated model is suitable for identifying pepper leaf and fruit diseases from digital images of pepper.
Synthesis and characterization of cost-effective and high-efficiency biochar for the adsorption of Pb2+ from wastewater
Authors: Bassareh Hatef , Karamzadeh Masoud , Movahedirad Salman
Published: September 2023

This study aimed to investigate the adsorption mechanism of Pb2+ in wastewater using activated carbon derived from inexpensive materials, specifically avocado, bitter orange, and walnut leaves, through a single-step chemical activation process. The activated carbon was prepared using sulfuric acid as an activator, with a particle size of 1 mm. The pyrolysis reactor (slow-pyrolysis) operated at 600 °C for 90 min with a nitrogen flow rate of 5 L/min. Batch experiments were conducted under various conditions to determine the optimal dosage (1.5 g/L), equilibrium contact time (180 min), and pH (6.5). The study focused on employing cost-effective and highly efficient adsorbents, namely biochar produced from tree leaves, for the adsorption process. The results indicated that the pseudo-second-order kinetic model accurately described the adsorption process, while the Freundlich isotherm model best fit the experimental data. These findings suggest that tree leaves can serve as cost-effective and efficient adsorbents for a wide range of applications. Furthermore, multiple adsorption factors were evaluated in batch mode, including contact duration, pH, adsorbent dosage, concentration of the Pb2+ solution, and temperature. The maximum adsorption capacities for the activated carbon derived from avocado, bitter orange, and walnut leaves were found to be 60.46, 59.42, and 58.48 mg/g, respectively. Thus, this study highlights the effectiveness and economic feasibility of using pyrolysis-derived activated carbon from low-cost materials for the removal of Pb2+ from wastewater.
Remnant liver function is associated with long-term survival in patients with hepatocellular carcinoma undergoing hepatectomy
Authors: Miki Atsushi , Sakuma Yasunaru , Watanabe Jun , Endo Kazuhiro , Sasanuma Hideki , Teratani Takumi , Lefor Alan Kawarai , Shimizu Atsushi , Kitayama Joji , Yasuda Yoshikazu , Sata Naohiro
Published: September 2023

It is important to assess the prognosis and intervene before and after surgery in patients with hepatocellular carcinoma. This study aims to elucidate the association of outcomes and residual liver function after hepatectomy. A total of 176 patients who underwent the initial resection for hepatocellular carcinoma between January 2011 and March 2021 at Jichi Medical University were included. Hepatic clearance of the remnant liver was measured using 99mTc-galactosyl serum albumin scintigraphy. The log-rank test was used to analyze survival using the Kaplan–Meier method. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival were calculated using Cox’s proportional hazard model. In multivariate analysis, microvascular invasion, intraoperative blood loss, and hepatic clearance of the remnant liver were independently associated with overall survival. Hepatic clearance of the remnant liver was independently associated with recurrence free survival. This is the first report to show that lower residual liver function is associated with shorter survival in patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative determination of remnant liver function may allow assessment of prognosis in patients planned to undergo resection of hepatocellular carcinoma. Preservation of liver functional reserve may be crucial for improved long-term outcomes after hepatectomy.
Understanding the influence of cation and anion migration on perovskite light-emitting diodes via transient response
Authors: Forozi Sowmeeh Paria , Zohorfazeli Mohammad , Yazdani Elnaz
Published: September 2023

Despite the rapid progress demonstrated in the efficiency of Perovskite light-emitting diodes (PeLEDs) in the past few years, ion migration has challenged the practical applications of these devices with undesirable hysteresis and degradation effect. Mobile ions in PeLEDs induced many unique and fast transient phenomena occurring on the time scale of microseconds to seconds and it is still far from clear how the underlying physical mechanism of ion motion-induced variation relates to the device performance. Therefore, in this work, we employ an ionic Drift–Diffusion Model (DDM) to evaluate measuring transient current response in a time scale of sub-seconds. The results show that spatial redistribution of ions within the perovskite results in dynamic electric field variation, which in turn, affects charge carrier injection and distribution. Moreover, the time delay between anion and cation migration leads to an unequal rate of charge carrier injection, hence the multi-stage behavior of the current–time response. It is also realized that the potential barrier of charge injection due to cation and anion accumulation at perovskite interfaces with electron and hole transporting layers reduces. Therefore, the facilitation of charge injection favors radiative recombination, and improved IQEs are expected at higher ion densities. It is found that the current–time response of the device gives beneficial information on cation and anion migration time scales. Choosing an appropriate scan rate in accordance with cation-related slow migration time is the first step to achieving reliable measurement procedures and hysteresis-free PeLED.