bluuebunny/crossref_metadata_2025 huggingface dataset:
LASSO-derived nomogram for early identification of pediatric monogenic lupus
Authors: Zhang Tian-Yu , Wang Wei , Gao Si-Hao , Yu Zhong-Xun , Wang Wei , Zhou Yu , Wang Chang-Yan , Jian Shan , Wang Lin , Gou Li-Juan , Li Ji , Ma Ming-Sheng , Song Hong-Mei
Published: July 2024

Background

Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients.

Methods

This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index.

Results

A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92–0.97).

Conclusions

We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds − 9.032299.

Graphical abstract
Maternal diseases and congenital anomalies of the kidney and urinary tract in offspring: a cohort study
Authors: Ma Qiang , Li Ya-Qi , Meng Qing-Tang , Yang Bo , Zhang Hai-Tao , Shi Hua , Liu Chang-You , Xiang Tian-Chao , Zhao Na , Rao Jia
Published: July 2024

Background

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of prenatally diagnosed developmental malformation. This study aimed to assess the relationship between maternal diseases and CAKUT in offspring.

Methods

This retrospective study enrolled all pregnant women registered from January 2020 to December 2022 at one medical center. Medical information on maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease was collected. Based on the records of ultrasound scanning during the third trimester, the diagnosis was classified as isolated urinary tract dilation (UTD) or kidney anomalies. Multivariate logistic regression was performed to establish models to predict antenatal CAKUT.

Results

Among the 19,656 pregnant women, perinatal ultrasound detected suspicious CAKUT in 114 (5.8/1000) fetuses, comprising 89 cases with isolated UTD and 25 cases with kidney anomalies. The risk of antenatal CAKUT was increased in the fetuses of mothers who experienced gestational diabetes, thyroid dysfunction, neuropsychiatric disease, anemia, ovarian and uterine disorders. A prediction model for isolated UTD was developed utilizing four confounding factors, namely gestational diabetes, gestational hypertension, maternal thyroid dysfunction, and hepatic disease. Similarly, a separate prediction model for kidney anomalies was established based on four distinct confounding factors, namely maternal thyroid dysfunction, gestational diabetes, disorders of ovarian/uterine, and kidney disease.

Conclusions

Isolated UTD and kidney anomalies were associated with different maternal diseases. The results may inform the clinical management of pregnancy and highlight potential differences in the genesis of various subtypes of CAKUT.

Graphical abstract
Intertidal and shallow subtidal marine tardigrades from the British Virgin Islands with a description of a new Batillipes (Heterotardigrada: Batillipedidae)
Authors: Bartels Paul J. , Fontoura Paulo , Nelson Diane R. , Kaczmarek Łukasz
Published: July 2024

This is the first survey of marine tardigrades from the British Virgin Islands, though two species were previously reported from St. Croix, U.S. Virgin Islands. In June 2016, we collected subtidal and intertidal sand samples from various locations throughout the British Virgin Islands. We found 602 tardigrades in 18 of 21 samples, and these included 12 taxa, one of which, Batillipes wyedeleinorum sp. nov., is new to science and described here. We compared abundance and species diversity in intertidal and subtidal samples and found significantly greater abundance in intertidal habitats but no significant difference in the number of observed species between the two habitats. We calculated Chao 1 species richness, which indicated higher estimated richness in intertidal habitats and 15 ± 3.7 species (x̅ ± SD) in both habitats combined. Non-metric Multidimensional Scaling revealed differences in species composition between the two habitats with some species showing clear preferences for one or the other.
Pharmacotherapy as an Augmentation to Bariatric Surgery for Obesity
Authors: Horváth Luděk , Mráz Miloš , Jude Edward B. , Haluzík Martin
Published: July 2024

A global obesity pandemic is one of the most significant health threats worldwide owing to its close association with numerous comorbidities such as type 2 diabetes mellitus, arterial hypertension, dyslipidemia, heart failure, cancer and many others. Obesity and its comorbidities lead to a higher rate of cardiovascular complications, heart failure and increased cardiovascular and overall mortality. Bariatric surgery is at present the most potent therapy for obesity, inducing a significant weight loss in the majority of patients. In the long-term, a substantial proportion of patients after bariatric surgery experience a gradual weight regain that may, in some, reach up to a presurgical body weight. As a result, anti-obesity pharmacotherapy may be needed in some patients after bariatric surgery to prevent the weight regain or to further potentiate weight loss. This article provides an overview of the use of anti-obesity medications as an augmentation to bariatric surgery for obesity. Despite relatively limited published data, it can be concluded that anti-obesity medication can serve as an effective adjunct therapy to bariatric surgery to help boost post-bariatric weight loss or prevent weight regain.
Targeting Neurotransmitter Systems in Bipolar Disorder: A comprehensive Review of novel pharmacological approaches
Authors: Siopa Carlos , Calaça Maria , Pestana Pedro Câmara , Novais Filipa
Published: July 2024

Purpose of Review

To critically assess the efficacy of novel pharmacological interventions in managing manic or hypomanic episodes in adult patients diagnosed with bipolar disorder.

Recent Findings

This systematic review synthesized findings from 11 prospective, double-blind, RCTs conducted between 2019 and 2023. The studies evaluated various agents, including melatonin, levetiracetam, palmitoylethanolamide, celecoxib, ebselen, endoxifen, spironolactone, clonidine, and vitamin B6, either as monotherapy or adjunctive therapy. Significant reductions in manic symptoms were observed with adjunctive melatonin, adjunctive levetiracetam, palmitoylethanolamide, endoxifen, and clonidine. In contrast, celecoxib, spironolactone, ebselen, sole melatonin, levetiracetam adjunctive to quetiapine, and vitamin B6 did not show statistically significant effects. Cognitive performance and sleep quality outcomes varied, with some substances showing improvements and others showing worsening effects.

This review highlights the potential of novel pharmacological interventions to enhance the management of manic or hypomanic episodes in bipolar disorder. By targeting different neurotransmitter systems, these substances offer alternative treatment possibilities that may benefit patients unresponsive to traditional therapies. The findings underscore the importance of continued research to expand therapeutic options, enabling more personalized and effective treatment strategies, and ultimately improving patient outcomes and quality of life in bipolar disorder management.
Taking care of inpatients with fragility hip fractures: the hip-padua osteosarcopenia (Hip-POS) fracture liaison service model
Authors: Arcidiacono G. P. , Ceolin C. , Sella S. , Camozzi V. , Bertocco A. , Torres M. O. , Rodà M. G. , Cannito M. , Berizzi A. , Romanato G. , Venturin A. , Cianci V. , Pizziol A. , Pala E. , Cerchiaro M. , Savino S. , Tessarin M. , Simioni P. , Sergi G. , Ruggieri P. , Giannini S. ,   the Hip-POS working group, Andaloro Carlotta , Bano Giulia , Boemo Deris Gianni , Bukli Ester , Cannavò Davide , Cecchinato Alberta , Dall’Agnol Martina , Rui Marina , Degan Mario , Dianin Marta , Diogo Martin , Ferrarese Michela , Finamoni Claudia , Guidolin Francesca , Storto Mario Rosario Lo , Marigo Elena , Masiero Stefano , Mian Caterina , Nesoti Maria Vittoria , Falb Mor Peleg , Russo Cristina , Simonato Cristina , Termini Giulia , Veronese Hillary , Zanchetta Francesca , Ziliotto Chiara
Published: July 2024

Purpose

Osteoporotic fragility fractures (FF), particularly those affecting the hip, represent a major clinical and socio-economic concern. These fractures can lead to various adverse outcomes, which may be exacerbated by the presence of sarcopenia, especially among older and frail patients. Early identification of patients with FF is crucial for implementing effective diagnostic and therapeutic strategies to prevent subsequent fractures and their associated consequences.

Methods

The Hip-POS program, implemented at Azienda Ospedale-Università Padova, is a Fracture Liaison Service (FLS) program to evaluate patients aged > 50 years old admitted with fragility hip fractures, involving an interdisciplinary team. After the identification of patients with hip fractures in the Emergency Department, a comprehensive evaluation is conducted to identify risk factors for further fractures, and to assess the main domains of multidimensional geriatric assessment, including muscle status. Patients are then prescribed with anti-fracture therapy, finally undergoing periodic follow-up visits.

Results

During the first five months, a total of 250 patients were evaluated (70.4% women, median age 85 years). Following assessment by the Hip-POS team, compared to pre-hospitalization, the proportion of patients not receiving antifracture therapy decreased significantly from 60 to 21%. The prescription rates of vitamin D and calcium increased markedly from 29.6% to 81%.

Conclusions

We introduced the Hip-POS program for the care of older adults with hip fractures. We aspire that our model will represent a promising approach to enhancing post-fracture care by addressing the multifactorial nature of osteoporosis and its consequences, bridging the gap in secondary fracture prevention, and improving patient outcomes.
TUMDOT–MUC: Data Collection and Processing of Multimodal Trajectories Collected by Aerial Drones
Authors: Kutsch Alexander , Margreiter Martin , Bogenberger Klaus
Published: July 2024

Currently available trajectory data sets undoubtedly provide valuable insights into traffic events, the behavior of road users and traffic flow theory, thus enabling a wide range of applications. However, there are still shortcomings that need to be addressed: (i) the continuous temporal recording (ii) of a coherent area covering several intersections (iii) with the detection of all road users, including pedestrians and cyclists. Therefore, this study focuses on the design of a large-scale aerial drone observation in the city of Munich, Germany, as well as the processing steps and the description of the resulting data set. Using twelve camera-equipped, unmanned aerial drones, the observation monitored an inner urban road section with a length of 700 m continuously for several hours during the afternoon peak hours on two working days. The trajectories of all road users were then extracted from the videos and post-processed in order to obtain a coherent and accurate data set. The resulting trajectories contain information on the category, dimensions, location, velocity, acceleration and orientation of each road user at each frame, merged continuously in time and space across several drone observation areas and subsequent time slots. The data, therefore, includes various interactions between different modes of motorized traffic and active mobility users like pedestrians and cyclists. The whole data set and the supporting data are available open source for research purposes to ensure global accessibility.
Uncovering the unique characteristics of different groups of 5-HT5AR ligands with reference to their interaction with the target protein
Authors: Kordylewski Szymon K. , Bugno Ryszard , Bojarski Andrzej J. , Podlewska Sabina
Published: July 2024

Background

The serotonin 5-HT5A receptor has attracted much more research attention, due to the therapeutic potential of its ligands being increasingly recognized, and the possibilities that lie ahead of these findings. There is a growing body of evidence indicating that these ligands have procognitive, pro-social, and anti-depressant properties, which offers new avenues for the development of treatments that could address socially important conditions related to the malfunctioning of the central nervous system. The aim of our study was to unravel the molecular determinants for 5-HT5AR ligands that govern their activity towards the receptor.

Methods

In response to the need for identification of molecular determinants for 5-HT5AR activity, we prepared a comprehensive collection of 5-HT5AR ligands, carefully gathering literature and patent data. Leveraging molecular modeling techniques, such as pharmacophore hypothesis development, docking, and molecular dynamics simulations enables to gain valuable insights into the specific interactions of 5-HT5AR ligand groups with the receptor.

Results

The obtained comprehensive set of 2160 compounds was divided into dozens of subsets, and a pharmacophore model was developed for each group. The results from the docking and molecular dynamics simulations have enabled the identification of crucial ligand–protein interactions that are essential for the compound's activity towards 5-HT5AR.

Conclusions

The findings from the molecular modeling study provide valuable insights that can guide medicinal chemists in the development of new 5-HT5AR ligands. Considering the pharmacological significance of these compounds, they have the potential to become impactful treatments for individuals and communities in the future. Understanding how different crystal/cryo-EM structures of 5-HT5AR affect molecular modeling experiments could have major implications for future computational studies on this receptor.

Graphical abstract
Developmental Dysplasia of the Hip and Laterality: The Importance of Graded Severity of the Contralateral Hip
Authors: Schaeffer Emily K. , Price Charles T. , Mulpuri Kishore ,   Global Hip Dysplasia (GHD) Study Group
Published: July 2024

Background

Laterality and bilaterality have been reported as prognostic variables in developmental dysplasia of the hip (DDH) outcomes. However, there is little clarity across the literature on the reporting of laterality in developmental dysplasia of the hip (DDH) due to the variability in severity of the condition. It is widely accepted that the left hip is most frequently affected; however, the true incidence of unilateral left, unilateral right and bilateral cases can be hard to quantify and compare across studies. The purpose of this study was to examine laterality accounting for graded severity in a multi-centre, international prospective observational study of infants with hip dysplasia to demonstrate the complexity of this issue.

Methods

A multi-centre, prospective hip dysplasia database was analyzed from 2010 to April 2015. Baseline diagnosis was used to classify patients into a graded laterality category accounting for hip status within the DDH spectrum.

Results

A total of 496 patients were included in the analysis; 328 were <6 months old at diagnosis and 168 were between 6 and 18 months old. Of these patients, 421 had at least one frankly dislocated hip. Unilateral left hip dislocations were most common, with 223 patients, followed by unilateral right and bilateral dislocations with 106 and 92 respectively. Stratifying these patients based on status of the contralateral hip, 54 unilateral left and 31 unilateral right dislocated patients also had a dysplastic or unstable contralateral hip. There were significantly fewer bilateral patients in the 6 to 18-month group (p = 0.0005). When classifying laterality by affected hip, bilaterality became the predominant finding, comprising 42% of all patients.

Conclusions

Findings from this multi-centre prospective study demonstrate the necessity to account for the graded severity in hip status when reporting DDH laterality. To accurately compare laterality across studies, a standardized, comprehensive classification should be established, as contralateral hip status may impact prognosis and treatment outcomes.

Level of Evidence

Level II Prognostic Study.
Observations of High Definition Symmetric Quasi‐Periodic Scintillations in the Mid‐Latitude Ionosphere With LOFAR
Authors: Trigg H. , Dorrian G. , Boyde B. , Wood A. , Fallows R. A. , Mevius M.
Published: July 2024

We present broadband ionospheric scintillation observations of highly defined symmetric quasi‐periodic scintillations (QPS: Maruyama, 1991, https://doi.org/10.1029/91rs00357) caused by plasma structures in the mid‐latitude ionosphere using the LOw Frequency ARray (LOFAR: van Haarlem et al., 2013, https://doi.org/10.1051/0004‐6361/201220873). Two case studies are shown, one from 15 December 2016, and one from 30 January 2018, in which well‐defined main signal fades are observed to be bounded by secondary diffraction fringing. The ionospheric plasma structures effectively behave as a Fresnel obstacle, in which steep plasma gradients at the periphery result in a series of decreasing intensity interference fringes, while the center of the structures largely block the incoming radio signal altogether. In particular, the broadband observing capabilities of LOFAR permit us to see considerable frequency dependent behavior in the QPSs which, to our knowledge, is a new result. We extract some of the clearest examples of scintillation arcs reported in an ionospheric context, from delay‐Doppler spectral analysis of these two events. These arcs permit the extraction of propagation velocities for the plasma structures causing the QPSs ranging from 50 to 00 m s−1, depending on the assumed altitude. The spacing between the individual plasma structures ranges between 5 and 20 km. The periodicities of the main signal fades in each event and, in the case of the 2018 data, co‐temporal ionosonde data, suggest the propagation of the plasma structures causing the QPSs are in the E‐region. Each of the two events is accurately reproduced using a thin screen phase model. Individual signal fades and enhancements were modeled using small variations in total electron content (TEC) amplitudes of order 1 mTECu, demonstrating the sensitivity of LOFAR to very small fluctuations in ionospheric plasma density. To our knowledge these results are among the most detailed observations and modeling of QPSs in the literature.
Submesoscale Processes in the Kuroshio Loop Current: Roles in Energy Cascade and Salt and Heat Transports
Authors: Tang Tian , Zhang Zhiwei , Zhang Jinchao , Zhang Xincheng , Sun Zhongbin , Feng Zhe
Published: July 2024

The Kuroshio Loop Current (KLC) is an important form of Kuroshio intrusion into the northeastern South China Sea (NESCS), which has significant influences on dynamical and biogeochemical processes in the NESCS. Recent studies suggested that the KLC is a hot spot of submesoscale processes (submesoscales) with spatiotemporal scales of O(1–10) km and O(1–10) days, but submesoscales' roles in energy cascade and salt and heat transports remain obscure. Here, we investigate this issue through analyzing outputs from a 1/48° simulation. The kinetic energy exchange rate between submesoscale and larger‐scale processes (KER) is overall positive in the KLC region, which suggests the dominance of forward cascade. The magnitude of KER is comparable with the temporal change rate of larger‐scale kinetic energy in the upper 200 m. We also find that magnitude and direction of KER are closely associated with strain rate and horizontal divergence of background flows, respectively. In addition, the KLC region shows elevated submesoscale salinity and heat diffusivities with magnitudes reaching O(102) m2 s−1. During the KLC period, horizontal mixing by submesoscales can transport 0.90 × 1013 kg salt and 0.71 × 1020 J heat westward into the NESCS interior, which are an order of magnitude larger than those caused by the mesoscale eddy shedding from the KLC. These results suggest that submesoscales play important roles not only in energy cascade but also in salt and heat transports in the KLC region. Therefore, the roles of submesoscales should be taken into account when studying energy, salt, and heat budgets in the NESCS.
Impacts of the Madden‐Julian Oscillation on Marginal Sea Heatwaves of the Southeastern Tropical Indian Ocean
Authors: Cui Zhanxian , Li Yuanlong , Guo Yaru , Wang Fan
Published: July 2024

Marginal seas of the southeastern tropical Indian Ocean (SETIO), including the South Java coasts and the Timor and Arafura Seas, are hotspots of large‐scale marine heatwaves (MHWs) in austral summer with notable impacts on local ecosystems. Yet, the prediction of these MHWs remains challenging. By analyzing 39 MHWs and 45 marine cold‐spells (MCSs) observed in the summers of 1982–2021, this study reveals a robust modulation effect of the Madden‐Julian Oscillation (MJO) on these events. The results show that 56% of MHWs and 51% of MCSs overlapped with MJO events, and their duration is systematically longer than others. Moreover, MHWs in phases 3–4 and MCSs in phases 6–7 of the real‐time multivariate MJO (RMM) index were nearly 2–3 times stronger in intensity than the others. The passage of MJOs drives prominent intraseasonal sea surface temperature (SST) variability in the SETIO through perturbing surface heat fluxes, which in turn modulates the occurrence of MHWs and MCSs. During RMM phases 1–2 (convective center over of the east of Africa or the central‐western Indian Ocean), the SETIO is controlled by a dry condition, with increased surface insolation and suppressed latent heat release. These anomalous fluxes drive a persistent SST increase, facilitating the emergence of strong and prolonged MHWs in the subsequent RMM phases 3–4. Further analysis suggests an 18% probability for MHWs in the SETIO 12 ± 10 days after Phase 1. Therefore, the MJO contributes to the predictability of MHWs/MCSs of the SETIO, with implications for predicting climate extremes and hazards.
Cosmic Rays Shed Light on Stone Age Timelines
Authors: Hasler Caroline
Published: July 2024

Signatures of a long-ago solar storm, recorded in tree rings, helped researchers date a 7,400-year-old settlement in northern Greece.
Comparison of Very Low Frequency Wave Intensities Measured by a Low‐Altitude Spacecraft and on the Ground
Authors: Němec F. , Drastichová K. , Manninen J. , Martinez‐Calderon C. , Shiokawa K. , Connors M.
Published: July 2024

We evaluate average wave intensities at frequencies up to 10 kHz measured by two ground stations in Canada and two others in Finland at auroral and subauroral latitudes over a full year, as well as by the low‐altitude DEMETER spacecraft during the years 2004–2010. Lightning location and energy data obtained by the World Wide Lightning Location Network, along with geomagnetic activity characterized by the Kp index, are further used. Latitudinal, diurnal, and annual variations are analyzed, and the global intensities measured on the ground and by the spacecraft are systematically compared for the first time. We show that lightning‐generated waves often dominate the measured wave intensities, particularly during the night, in summer, and at higher frequencies. DEMETER observations, supported by ray‐tracing analysis, reveal a significant role of nonducted lightning‐generated whistler propagation between the hemispheres. Finally, the wave intensity response to geomagnetic activity variations is quite different on the ground compared to in space. While spacecraft‐measured wave intensities are considerably larger during periods of enhanced geomagnetic activity, the ground‐based intensities are only sporadically enhanced during geomagnetically active periods.
Learning Distributed Parameters of Land Surface Hydrologic Models Using a Generative Adversarial Network
Authors: Sun Ruochen , Pan Baoxiang , Duan Qingyun
Published: July 2024

Land surface hydrologic models adeptly capture crucial terrestrial processes with a high level of spatial detail. Typically, these models incorporate numerous uncertain, spatially varying parameters, the specification of which can profoundly impact the simulation capabilities. There is a longstanding tradition wherein parameter calibration has served as the conventional procedure to enhance model performance. However, calibrating distributed land surface hydrologic models presents a great challenge, often resulting in uneven spatial performance due to the compression of information inherent in model outputs and observations into a single‐value objective function. To address this problem, we propose a novel Generative Adversarial Network‐based Parameter Optimization (GAN‐PO) method. By leveraging a deep neural network to discern model spatial biases, we train a generative network to produce spatially coherent parameter fields, minimizing distinctions between simulations and observations. By leveraging neural network‐based surrogate models to make the physical model differentiable, we employ GAN‐PO to calibrate the Variable Infiltration Capacity (VIC) model against evapotranspiration (ET) over China's Huaihe basin. The results show that GAN‐PO can diminish errors in simulated ET derived from default parameters across nearly all grid cells within the study region, surpassing the conventional calibration approach based on the parameter regionalization technique. Ablation analysis indicates that relying solely on the traditional loss could lead to deteriorated model performance, underscoring the crucial role of the discriminator. Notably, due to the discriminator's explicit identification of model spatial biases, GAN‐PO excels in maintaining spatial consistency, outperforming the state‐of‐the‐art differentiable parameter learning (dPL) method in terms of model spatial performance.
Thalamocortical functional connectivity and rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression
Authors: Tu Pei-Chi , Chang Wan-Chen , Su Tung-Ping , Lin Wei-Chen , Li Cheng-Ta , Bai Ya-Mei , Tsai Shih-Jen , Chen Mu-Hong
Published: July 2024

Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine’s antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.
Development and validation of a clinical nomogram to predict prostatic inflammation in men with lower urinary tract symptoms
Authors: Gravas Stavros , De Nunzio Cosimo , Campos Pinheiro Luís , Ponce de León Javier , Skriapas Konstantinos , Milad Ziad , Lombardo Riccardo , Medeiros Mariana , Makrides Pantelis , Samarinas Michael , Gacci Mauro
Published: July 2024

Background

Prostatic inflammation is an important etiological component of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). The Prostatic Inflammation Nomogram Study (PINS) aimed to develop and validate a nomogram for predicting the presence of prostatic inflammation in men with LUTS.

Methods

This non-interventional, cross-sectional, prospective study was conducted in six secondary/tertiary centers across Cyprus, Greece, Italy, Portugal, and Spain. Men (≥40 years) with BPH/LUTS scheduled to undergo prostatic surgery or transrectal ultrasound-guided (TRUS) prostate biopsy were included. Fifteen demographic and clinical participant characteristics were selected as possible predictors of prostatic inflammation. The presence of inflammation (according to Irani score) in the prostatic tissue samples obtained from surgery/TRUS biopsy was determined. The effect of each characteristic on the likelihood a prostate specimen demonstrated inflammation (classified by Irani score into two categories, 0–2 [no/minimal inflammation] or 3–6 [moderate/severe inflammation]) was assessed using multiple logistic regression. A nomogram was developed and its discriminatory ability and validity were assessed.

Results

In total, 423 patients (mean age 68.9 years) were recruited. Prostate volume ultrasound (PVUS) > 50 mL, history of urinary tract infection (UTI) treatment, presence of diabetes, and International Prostate Symptom Score (IPPS) Storage score were statistically significant predictors of Irani classification. Logistic regression demonstrated a statistically significant effect for leucocytes detected via urine dipstick, presence of diabetes, PVUS > 50 mL, history of UTIs, and higher IPSS Storage score for the odds of an inflammatory score category of 3–6 versus 0–2. The nomogram had a concordance index of 0.71, and good internal validity.

Conclusions

The nomogram developed from PINS had good predictive ability and identified various characteristics to be predictors of prostatic inflammation. Use of the nomogram may aid in individualizing treatment for LUTS, by identifying individuals who are candidates for therapies targeting prostatic inflammation.
Reasons for non-feasibility of therapeutic drug monitoring of oral targeted therapies in oncology – an analysis of the closed cohorts of a multicentre prospective study
Authors: van der Kleij Maud B. A. , Guchelaar Niels A. D. , Meertens Marinda , Westerdijk Kim , Giraud Eline L. , Bleckman Roos F. , Groenland Stefanie L. , van Eerden Ruben A. G. , Imholz Alex L. T. , Vulink Annelie J. E. , Otten Hans-Martin , Fiebrich-Westra Helle-Brit , Lubberman Floor J. E. , Desar Ingrid M. E. , Moes Dirk-Jan A. R. , Touw Daan J. , Koolen Stijn L. W. , Gelderblom Hans , Reyners An K. L. , van Erp Nielka P. , Mathijssen Ron H. J. , Huitema Alwin D. R. ,   Dutch Pharmacology Oncology Group (DPOG), Steeghs Neeltje
Published: July 2024

Background

Therapeutic drug monitoring (TDM) – performing dose adjustments based on measured drug levels and established pharmacokinetic (PK) targets – could optimise treatment with drugs that show large interpatient variability in exposure. We evaluated the feasibility of TDM for multiple oral targeted therapies. Here we report on drugs for which routine TDM is not feasible.

Methods

We evaluated drug cohorts from the Dutch Pharmacology Oncology Group – TDM study. Based on PK levels taken at pre-specified time points, PK-guided interventions were performed. Feasibility of TDM was evaluated, and based on the success and practicability of TDM, cohorts could be closed.

Results

For 10 out of 24 cohorts TDM was not feasible and inclusion was closed. A high incidence of adverse events resulted in closing the cabozantinib, dabrafenib/trametinib, everolimus, regorafenib and vismodegib cohort. The enzalutamide and erlotinib cohorts were closed because almost all PK levels were above target. Other, non-pharmacological reasons led to closing the palbociclib, olaparib and tamoxifen cohort.

Conclusions

Although TDM could help personalising treatment for many drugs, the above-mentioned reasons can influence its feasibility, usefulness and clinical applicability. Therefore, routine TDM is not advised for cabozantinib, dabrafenib/trametinib, enzalutamide, erlotinib, everolimus, regorafenib and vismodegib. Nonetheless, TDM remains valuable for individual clinical decisions.
Aggregation promotes charge separation in fullerene-indacenodithiophene dyad
Authors: Wang Chong , Wu Bo , Li Yang , Zhou Shen , Wu Conghui , Dong Tianyang , Jiang Ying , Hua Zihui , Song Yupeng , Wen Wei , Tian Jianxin , Chai Yongqiang , Wen Rui , Wang Chunru
Published: July 2024

Fast photoinduced charge separation (CS) and long-lived charge-separated state (CSS) in small-molecules facilitate light-energy conversion, while simultaneous attainment of both remains challenging. Here we accomplish this through aggregation based on fullerene-indacenodithiophene dyads. Transient absorption spectroscopy reveals that, compared to solution, the CS time in aggregates is accelerated from 41.5 ps to 0.4 ps, and the CSS lifetime is prolonged from 311.4 ps to 40 μs, indicating that aggregation concomitantly promotes fast CS and long-lived CSS. Fast CS arises from the hot charge-transfer states dissociation, opening up additional resonant channels to free carriers (FCs); subsequently, charge recombination into intramolecular triplet CSS becomes favorable mediated by spin-uncorrelated FCs. Different from fullerene/indacenodithiophene blends, the unique CS mechanism in dyad aggregates reduces the long-lived CSS dependence on molecular order, resulting in a CSS lifetime 200 times longer than blends. This endows the dyad aggregates to exhibit both photoelectronic switch properties and superior photocatalytic capabilities.
Demonstration for cold atmospheric pressure plasma jet operation and antibacterial action in microgravity
Authors: Rouillard A. , Escot Bocanegra P. , Stancampiano A. , Dozias S. , Lemaire J. , Pouvesle J. M. , Robert E. , Brulé-Morabito F. , Demasure M. , Rouquette S.
Published: July 2024

Cold atmospheric pressure plasma (ionized gas) is an innovative medical tool for the treatment of infected wounds thanks to its potential to inactivate drug-resistant microorganisms and promote tissue regeneration and vascularization. The low power consumption, compactness, and versatility of Cold Atmospheric Pressure Plasma (CAPP) devices make them an ideal tool for risk mitigation associated with human spaceflights. This work presents results in microgravity on the operability of CAPP and its antimicrobial effect. The experiments carried out in parabolic flights make it possible to optimize the treatment conditions (i.e., the distance, the gas mixture) and to obtain the rapid inactivation (<15 s) of Escherichia coli samples. Interestingly, the inactivation efficiency of CAPP was higher during parabolic flights than under terrestrial conditions. Overall, these results encourage the further development of CAPP medical devices for its implementation during human spaceflights.
A randomised trial of malaria vaccine R21/Matrix-M™ with and without antimalarial drugs in Thai adults
Authors: Hanboonkunupakarn Borimas , Mukaka Mavuto , Jittamala Podjanee , Poovorawan Kittiyod , Pongsuwan Pongphaya , Stockdale Lisa , Provstgaard-Morys Samuel , Chotivanich Kesinee , Tarning Joel , Hoglund Richard M. , Chimjinda Natenapa , Ewer Katie , Ramos-Lopez Fernando , Day Nicholas P. J. , Dondorp Arjen M. , Hill Adrian V. , White Nicholas J. , von Seidlein Lorenz , Pukrittayakamee Sasithon
Published: July 2024

In preparation for mass vaccinations with R21/Matrix-M™ combined with mass administrations of dihydroartemisinin, piperaquine, and a single low dose primaquine we assessed the tolerability, safety, and potential interactions of this combination affecting immunogenicity or pharmacokinetics. 120 healthy Thai volunteers were randomised to receive either antimalarials combined with vaccinations (n = 50), vaccinations alone (n = 50), or antimalarials only (n = 20). Three rounds of vaccines and antimalarials were administered one month apart. The vaccine was well tolerated alone and in combination with the antimalarials. None of the participants failed completion of the 3-dose vaccine course. There was no significant difference in the vaccine immunogenicity or in the pharmacokinetics of piperaquine given individually or in combination. This study supports proceeding to a large trial of mass vaccinations with R21/Matrix-M™ combined with mass antimalarial administration in Bangladesh.
16S rRNA, metagenomics and 2bRAD-M sequencing to decode human thanatomicrobiome
Authors: Huang Xin , Zeng Jianye , Li Shilin , Chen Ji , Wang Hongyan , Li Chengtao , Zhang Suhua
Published: July 2024

Microorganisms are essential in the decomposition of corpses and play a significant role in forensic science. However, previous studies have primarily focused on animal remains, specifically the gut, skin, and burial environment. Insufficient research has been conducted on the microbiota of human cadavers, especially in cases of advanced decomposition and additional tissues, resulting in a lack of relevant reference data. In this study, the microbiota of eight cadavers at different stages of decomposition were detected using 16S rRNA, metagenomic sequencing and 2bRAD-M sequencing. Nine different sites, including oral and nasal cavities, heart, liver, spleen, lung, kidney, muscle and gut, were analysed and the efficacy of these methods was evaluated. The results showed that 16S rRNA sequencing was the most cost-effective method for the study of cadavers in the early stages of decomposition, whereas for cadaveric tissues in the late stages of decomposition, 2bRAD-M could overcome host contamination more effectively than metagenomic sequencing. This paves the way for new opportunities in data retrieval and promotes in-depth investigations into the microbiota.
40 years of forest dynamics and tree demography in an intact tropical forest at M’Baïki in central Africa
Authors: Bénédet Fabrice , Gourlet-Fleury Sylvie , Allah-Barem Félix , Baya Fidèle , Beina Denis , Cornu Guillaume , Dimanche Luc , Dubiez Émilien , Forni Éric , Freycon Vincent , Mortier Frédéric , Ouédraogo Dakis-Yaoba , Picard Nicolas , Rossi Vivien , Semboli Olivia , Yalibanda Yves , Yongo-Bombo Olga , Fayolle Adeline
Published: July 2024

A vast silvicultural experiment was set up in 1982 nearby the town of M’Baïki in the Central African Republic to monitor the recovery of tropical forests after disturbance. The M’Baïki experiment consists of ten 4-ha Permanent Sample Plots (PSPs) that were assigned to three silvicultural treatments in 1986 according to a random block design. In each plot, all trees with a girth at breast height greater than 30 cm were spatially located, numbered, measured, and determined botanically. Girth, mortality and newly recruited trees, were monitored almost annually over the 1982–2022 period with inventory campaigns for 35 years. The data were earlier used to fit growth and population models, to study the species composition dynamics, and the effect of silvicultural treatments on tree diversity and aboveground biomass. Here, we present new information on the forest stand structure dynamics and tree demography. The data released from this paper cover the three control plots and constitute a major contribution for further studies about the biodiversity of intact tropical forests.
BULL Database – Spanish Basin attributes for Unravelling Learning in Large-sample hydrology
Authors: Senent-Aparicio Javier , Castellanos-Osorio Gerardo , Segura-Méndez Francisco , López-Ballesteros Adrián , Jimeno-Sáez Patricia , Pérez-Sánchez Julio
Published: July 2024

We present a novel basin dataset for large-sample hydrological studies in Spain. BULL comprises data for 484 basins, combining hydrometeorological time series with several attributes related to geology, soil, topography, land cover, anthropogenic influence and hydroclimatology. Thus, we followed recommendations in the CARAVAN initiative for generating a truly open global hydrological dataset to collect these attributes. Several climatological data sources were used, and their data were validated by hydrological modelling. One of the main novelties of BULL compared to other national-scale datasets is the analysis of the hydrological alteration of the basins included in this dataset. This aspect is critical in countries such as Spain, which are characterised by rivers suffering from the highest levels of anthropisation. The BULL dataset is freely available at https://zenodo.org/records/10605646.
Foam density mapping via THz imaging
Authors: Catapano Ilaria , Zappia Sonia , Iaccarino Paolo , Scapaticci Rosa , Di Maio Ernesto , Crocco Lorenzo
Published: July 2024

Plastic foams, near-ubiquitous in everyday life and industry, show properties that depend primarily on density. Density measurement, although straightforward in principle, is not always easy. As such, while several methods are available, plastic foam industry is not yet supported with a standard technique that effectively enables to control density maps. To overcome this issue, this paper proposes Terahertz (THz) time-of-flight imaging using normal reflection measurements as a fast, relatively cheap, contactless, non-destructive and non-dangerous way to map plastic foam density, based on the expected relationship between density and refractive index. The approach is demonstrated in the case of polypropylene foams. First, the relationship between the estimated effective refractive index and the polypropylene foam density is derived by characterizing a set of carefully crafted samples having uniform density in the range 70–900 kg/m3. The obtained calibration curve subtends a linear relationship between the density and the refractive index in the range of interest. This relationship is validated against a set of test samples, whose estimated average densities are consistent with the nominal ones, with an absolute error lower than 10 kg/m3 and a percentage error on the estimate of 5%. Exploiting the calibration curve, it is possible to build quantitative images depicting the spatial distribution of the sample density. THz images are able to reveal the non-uniform density distribution of some samples, which cannot be appreciated from visual inspection. Finally, the complex spatial density pattern of a graded foam sample is characterized and quantitatively compared with the density map obtained via X-ray microscopy. The comparison confirms that the proposed THz approach successfully determines the density pattern with an accuracy and a spatial scale variability compliant with those commonly required for plastic foam density estimate.
Enhancement of porous asphalt mixtures modified with various fibers and ethylene–vinyl acetate polymer
Authors: Nazmey Kareem G. , Eisa Mohammed S. , Morsi Ahmed Gamal M. , Debaiky Ahmed S.
Published: July 2024

Porous asphalt mixture is conventional hot mix asphalt (HMA) with substantially decreased fines, which produces an open-graded mixture that enables the water to flow through an interconnected void space. Porous asphalt is a permeable system that has a lot of benefits. However, because of its open structure, the durability of this mixture decreases, and both its stability and resilient modulus are much lower compared to the dense conventional asphalt mixtures. Also, the high void percentage may lead to an increase in the draindown proportion. Fibers (cellulose or mineral) and polymer-modified binders are recommended for porous asphalt mixtures, especially in hot and moderate climates. The objective of this study is to improve the porous asphalt mixture's performance by using ethylene–vinyl acetate (EVA) polymer-modified bitumen. Two types of fibers (cellulose fibers and glass wool fibers) were used, separately to determine the control mixture. Four different proportions of EVA polymer were added to the bitumen (1%, 2%, 3%, and 4%) and Scanning Electron Microscopy (SEM) was used for better investigating of the bitumen microstructure, then The Marshall mix design was used to determine the optimum EVA content (OEC) for the porous asphalt mixture. Several performance tests were conducted to investigate the characteristics of the porous asphalt mixture, such as the infiltration rate, binder draindown, the wheel track and the cantabro abrasion tests. The findings of the study conclude that the addition of EVA polymer to the porous asphalt mixtures enhances the performance as it increases stability by 20.8% and the infiltration rate by 20.6%. It decreases binder draindown proportion by 33.3%, cantabro abrasion loss by 25.1% and the rut depth at 5,000 cycles and 10,000 cycles by 29.8% and 19.7%, respectively.
Phasor-based analysis of a neuromorphic architecture for microwave sensing
Authors: Soleimani Ashkan , Forooraghi Keyvan , Atlasbaf Zahra
Published: July 2024

This article presents a design procedure for implementing artificial neural networks (ANNs) using conventional microwave components at the hardware level with potential applications in radar and remote sensing. The main objective is to develop structured hardware design methods for implementing artificial neurons, utilizing microwave devices to create neuromorphic devices compatible with high-frequency electromagnetic waves. The research aims to address the challenge of encoding and modulating information in electromagnetic waves into a format suitable for the neuromorphic device by using frequency-modulated information instead of intensity-modulated information. It also proposes a method for integrating principal component analysis as a dimensionality reduction technique with the implementation of ANNs on a single hardware. As a dummy task, the process outlined here is used to implement an artificial neural network at the hardware level, with a specific emphasis on creating hardware that is capable of performing matrix multiplications in the form of dot products while also being able to extract the resulting data in an interpretable manner. The proposed implementation involves the use of directional couplers to implement weights and sample the resulting signal at specific intervals to obtain the multiplication result.