bluuebunny/crossref_metadata_2025 huggingface dataset:
Desymmetric homologating annulation to access chiral pentafulvenes and their application in bioimaging
Authors: Singh Sanjay , Saini Ravi , Joshi Akshay , Singh Neetu , Singh Ravi P.
Published: March 2024

The architectural design of polycyclic/multisubstituted pentafulvenes has demonstrated great potential for the development of electrochromic materials and biologically active motifs. Unfortunately, the enantioselective construction of such distinctive cores with all carbon quaternary chiral centers has remained untouched to date. Herein, we disclose an enantioselective homologating annulation of cyclopent-4-ene-dione with 3-cyano-4-methylcoumarins through L-tert-leucine derived thiourea catalysis, affording a wide range of enantioenriched polycyclic multisubstituted embedded aminopentafulvenes with excellent stereocontrol (up to 99:1 er) and chemical yields up to 87%. A detailed photophysical and cytotoxicity analysis of racemic and chiral homologated adducts unveils the exceptional behavior of chiral adducts over their racemic analogs, highlighting the importance of stereoselectivity of the developed scaffolds. A cellular uptake experiment in a mammalian fibroblast cell line confirmed the potential of developed polycyclic aminopentafulvene cores as a highly promising labeling dye that can be utilized for bioimaging without any adverse effects.
Loss of WIPI4 in neurodegeneration causes autophagy-independent ferroptosis
Authors: Zhu Ye , Fujimaki Motoki , Snape Louisa , Lopez Ana , Fleming Angeleen , Rubinsztein David C.
Published: March 2024

β-Propeller protein-associated neurodegeneration (BPAN) is a rare X-linked dominant disease, one of several conditions that manifest with neurodegeneration and brain iron accumulation. Mutations in the WD repeat domain 45 (WDR45) gene encoding WIPI4 lead to loss of function in BPAN but the cellular mechanisms of how these trigger pathology are unclear. The prevailing view in the literature is that BPAN is simply the consequence of autophagy deficiency given that WIPI4 functions in this degradation pathway. However, our data indicate that WIPI4 depletion causes ferroptosis—a type of cell death induced by lipid peroxidation—via an autophagy-independent mechanism, as demonstrated both in cell culture and in zebrafish. WIPI4 depletion increases ATG2A localization at endoplasmic reticulum–mitochondrial contact sites, which enhances phosphatidylserine import into mitochondria. This results in increased mitochondrial synthesis of phosphatidylethanolamine, a major lipid prone to peroxidation, thus enabling ferroptosis. This mechanism has minimal overlap with classical ferroptosis stimuli but provides insights into the causes of neurodegeneration in BPAN and may provide clues for therapeutic strategies.
Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy
Authors: Tan C. L. , Lindner K. , Boschert T. , Meng Z. , Rodriguez Ehrenfried A. , De Roia A. , Haltenhof G. , Faenza A. , Imperatore F. , Bunse L. , Lindner J. M. , Harbottle R. P. , Ratliff M. , Offringa R. , Poschke I. , Platten M. , Green E. W.
Published: March 2024

The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing. PredicTCR identifies tumor-reactive TCRs in TILs from diverse cancers better than previous gene set enrichment-based approaches, increasing specificity and sensitivity (geometric mean) from 0.38 to 0.74. By predicting tumor-reactive TCRs in a matter of days, TCR clonotypes can be prioritized to accelerate the manufacture of personalized T cell therapies.
A revisited history of cacao domestication in pre-Columbian times revealed by archaeogenomic approaches
Authors: Lanaud Claire , Vignes Hélène , Utge José , Valette Gilles , Rhoné Bénédicte , Garcia Caputi Mariella , Angarita Nieto Natalia Sofía , Fouet Olivier , Gaikwad Nilesh , Zarrillo Sonia , Powis Terry G. , Cyphers Ann , Valdez Francisco , Olivera Nunez S. Quirino , Speller Camilla , Blake Michael , Valdez Fred , Raymond Scott , Rowe Sarah M. , Duke Guy S. , Romano Francisco Ernesto , Loor Solórzano Rey Gaston , Argout Xavier
Published: March 2024

Humans have a long history of transporting and trading plants, contributing to the evolution of domesticated plants. Theobroma cacao originated in the Neotropics from South America. However, little is known about its domestication and use in these regions. In this study, ceramic residues from a large sample of pre-Columbian cultures from South and Central America were analyzed using archaeogenomic and biochemical approaches. Here we show, for the first time, the widespread use of cacao in South America out of its native Amazonian area of origin, extending back 5000 years, likely supported by cultural interactions between the Amazon and the Pacific coast. We observed that strong genetic mixing between geographically distant cacao populations occurred as early as the middle Holocene, in South America, driven by humans, favoring the adaptation of T. cacao to new environments. This complex history of cacao domestication is the basis of today's cacao tree populations and its knowledge can help us better manage their genetic resources.
Electrochemical sensor based on PEDOT/CNTs-graphene oxide for simultaneous determination of hazardous hydroquinone, catechol, and nitrite in real water samples
Authors: Ahmed Yousef M. , Eldin Mahmoud A. , Galal Ahmed , Atta Nada F.
Published: March 2024

Hydroquinone (HQ), catechol (CC) and nitrite (NT) are considered aquatic environmental pollutants. They are highly toxic, harm humans’ health, and damage the environment. Thus, in the present work we introduce a simple and efficient electrochemical sensor for determination of HQ, CC, and NT simultaneously in wastewater sample. The sensor is fabricated by modifying the surface of a glassy carbon electrode (GCE) by two successive thin films from poly(3,4-ethylenedioxythiophene) (PEDOT) and a mixture of carbon nanotubes-graphene oxide (CNT-GRO). Under optimized conditions the HQ, CC, and NT are successfully detected simultaneously in wastewater sample with changing their concentrations in the ranges (0.04 → 100 µM), (0.01 → 100 µM) and (0.05 → 120 µM), the detection limits are 8.5 nM, 3.8 nM and 6.1 nM, respectively. Good potential peak separations: 117 mV and 585 mV are obtained between the HQ-CC, and CC-NT. The sensor has an excellent catalytic capability toward the oxidation of HQ, CC, and NT due to good synergism between its composite components: PEDOT, GRO and CNTs. The features of the sensor are large active surface area, good electrical conductivity, perfect storage stability, good reproducibility, anti-interference capability and accepted recovery rate for HQ, CC, and NT determination in wastewater sample.
Distribution of exchangeable Ca2+ during the process of Larix decidua Mill. pollination and germination
Authors: Rafińska Katarzyna , Niedojadło Katarzyna , Świdziński Michał , Bednarska-Kozakiewicz Elżbieta
Published: March 2024

The involvement of Ca2+ ions in angiosperms sexual processes is well established, while in gymnosperms, such knowledge remains limited and is still a topic of discussion. In this study, we focused on Larix decidua, using Alizarin-red S staining and the pyroantimonate method to examine the tissue and subcellular distribution of free and loosely bound Ca2+ ions at different stages of the male gametophyte's development and its interaction with the ovule. Our findings show that in larch, both the germination of pollen grains and the growth of pollen tubes occur in an environment rich in Ca2+. These ions play a crucial role in the adhesion of the pollen grain to the stigmatic tip and its subsequent movement to the micropylar canal. There is a significant presence of free and loosely bound Ca2+ ions in both the fluid of the micropylar canal and the extracellular matrix of the nucellus. As the pollen tube extends through the nucellus, we observed a notable accumulation of Ca2+ ions just above the entry to the mature archegonium, a region likely crucial for the male gametophyte's directional growth. Meanwhile, the localized presence of free and loosely bound Ca2+ ions within the egg cell cytoplasm may inhibit the pollen tubes growth and rupture, playing an important role in fertilization.
An analytical approach to engineer multistability in the oscillatory response of a pulse-driven ReRAM
Authors: Ascoli Alon , Schmitt Nicolas , Messaris Ioannis , Demirkol Ahmet Samil , Strachan John Paul , Tetzlaff Ronald , Chua Leon
Published: March 2024

A nonlinear system, exhibiting a unique asymptotic behaviour, while being continuously subject to a stimulus from a certain class, is said to suffer from fading memory. This interesting phenomenon was first uncovered in a non-volatile tantalum oxide-based memristor from Hewlett Packard Labs back in 2016 out of a deep numerical investigation of a predictive mathematical description, known as the Strachan model, later corroborated by experimental validation. It was then found out that fading memory is ubiquitous in non-volatile resistance switching memories. A nonlinear system may however also exhibit a local form of fading memory, in case, under an excitation from a given family, it may approach one of a number of distinct attractors, depending upon the initial condition. A recent bifurcation study of the Strachan model revealed how, under specific train stimuli, composed of two square pulses of opposite polarity per cycle, the simplest form of local fading memory affects the transient dynamics of the aforementioned Resistive Random Access Memory cell, which, would asymptotically act as a bistable oscillator. In this manuscript we propose an analytical methodology, based on the application of analysis tools from Nonlinear System Theory to the Strachan model, to craft the properties of a generalised pulse train stimulus in such a way to induce the emergence of complex local fading memory effects in the nano-device, which would consequently display an interesting tuneable multistable oscillatory response, around desired resistance states. The last part of the manuscript discusses a case study, shedding light on a potential application of the local history erase effects, induced in the device via pulse train stimulation, for compensating the unwanted yet unavoidable drifts in its resistance state under power off conditions.
Dynamic performance of rotor-side nonlinear control technique for doubly-fed multi-rotor wind energy based on improved super-twisting algorithms under variable wind speed
Authors: Benbouhenni Habib , Yessef Mourad , Colak Ilhami , Bizon Nicu , Kotb Hossam , AboRas Kareem M. , ELrashidi Ali
Published: March 2024

The paper proposes a nonlinear controller called dual super-twisting sliding mode command (DSTSMC) for controlling and regulating the rotor side converter (RSC) of multi-rotor wind power systems that use doubly-fed induction generators. It was proposed that this controller be developed as an alternative to the direct power control (DPC), which makes use of a pulse width modulation (PWM) strategy to regulate the RSC's functioning. Overcoming the power/current quality issue with the proposed technique (DPC-DSTSMC-PWM) is characterized by great robustness and excellent performance. The designed strategy was contrasted with the standard method of control and other methods already in use. So, the unique proposed control strategy’s robustness, performance, efficiency, and efficacy in enhancing system characteristics were tested and validated in Matlab/Simulink. In both tests, the proposed method resulted in significant improvements, reducing active power ripples by 83.33%, 57.14%, and 48.57% in the proposed tests. When compared with the traditional regulation method, the reduction rates of reactive power ripples are 64.06%, 52.47%, and 68.7% in the tests. However, in contrast to the conventional method, the proposed tests showed a decrease of between 72.46%, 50%, and 76.22% in the value of total harmonic distortion (THD) of the provided currents. These ratios show how effective the proposed plan is in ameliorating and enhancing aspects of the energy system.
Development of risk prediction nomogram for neonatal sepsis in Group B Streptococcus-colonized mothers: a retrospective study
Authors: Wu Mengqi , Deng Yanbing , Wang Xinye , He Baomei , Wei Fangqiang , Zhang Ying
Published: March 2024

Neonatal clinical sepsis is recognized as a significant health problem, This study sought to identify a predictive model of risk factors for clinical neonatal sepsis. A retrospective study was conducted from 1 October 2018 to 31 March 2023 in a large tertiary hospital in China. Neonates were divided into patients and controls based on the occurrence of neonatal sepsis. A multivariable model was used to determine risk factors and construct models.The utilization and assessment of model presentation were conducted using Norman charts and web calculators, with a focus on model differentiation, calibration, and clinical applicability (DCA). Furthermore, the hospital’s data from 1 April 2023 to 1 January 2024 was utilized for internal validation. In the modelling dataset, a total of 339 pairs of mothers and their newborns were included in the study and divided into two groups: patients (n = 84, 24.78%) and controls (n = 255, 75.22%). Logistic regression analysis was performed to examine the relationship between various factors and outcome. The results showed that maternal age < 26 years (odds ratio [OR] = 2.16, 95% confidence interval [CI] 1.06–4.42, p = 0.034), maternal gestational diabetes (OR = 2.17, 95% CI 1.11–4.27, p = 0.024), forceps assisted delivery (OR = 3.76, 95% CI 1.72–5.21, p = 0.032), umbilical cord winding (OR = 1.75, 95% CI 1.32–2.67, p = 0.041) and male neonatal sex (OR = 1.59, 95% CI 1.00–2.62, p = 0.050) were identified as independent factors influencing the outcome of neonatal clinical sepsis. A main effects model was developed incorporating these five significant factors, resulting in an area under the curve (AUC) value of 0.713 (95% CI 0.635–0.773) for predicting the occurrence of neonatal clinical sepsis. In the internal validation cohort, the AUC value of the model was 0.711, with a 95% CI of 0.592–0.808. A main effects model incorporating the five significant factors was constructed to help healthcare professionals make informed decisions and improve clinical outcomes.
Ultra-high-frequency ECG volumetric and negative derivative epicardial ventricular electrical activation pattern
Authors: Leinveber Pavel , Halamek Josef , Curila Karol , Prinzen Frits , Lipoldova Jolana , Matejkova Magdalena , Smisek Radovan , Plesinger Filip , Nagy Andrej , Novak Miroslav , Viscor Ivo , Vondra Vlastimil , Jurak Pavel
Published: March 2024

From precordial ECG leads, the conventional determination of the negative derivative of the QRS complex (ND-ECG) assesses epicardial activation. Recently we showed that ultra-high-frequency electrocardiography (UHF-ECG) determines the activation of a larger volume of the ventricular wall. We aimed to combine these two methods to investigate the potential of volumetric and epicardial ventricular activation assessment and thereby determine the transmural activation sequence. We retrospectively analyzed 390 ECG records divided into three groups-healthy subjects with normal ECG, left bundle branch block (LBBB), and right bundle branch block (RBBB) patients. Then we created UHF-ECG and ND-ECG-derived depolarization maps and computed interventricular electrical dyssynchrony. Characteristic spatio-temporal differences were found between the volumetric UHF-ECG activation patterns and epicardial ND-ECG in the Normal, LBBB, and RBBB groups, despite the overall high correlations between both methods. Interventricular electrical dyssynchrony values assessed by the ND-ECG were consistently larger than values computed by the UHF-ECG method. Noninvasively obtained UHF-ECG and ND-ECG analyses describe different ventricular dyssynchrony and the general course of ventricular depolarization. Combining both methods based on standard 12-lead ECG electrode positions allows for a more detailed analysis of volumetric and epicardial ventricular electrical activation, including the assessment of the depolarization wave direction propagation in ventricles.
The role of fines in espresso extraction dynamics
Authors: Smrke Samo , Eiermann André , Yeretzian Chahan
Published: March 2024

The impact of particle size distribution of coffee grounds on espresso extraction was explored. Finely ground coffee for espresso has a characteristically bimodal particle size distribution. For a given median grind size, different grinding technologies can yield a different share of fines (particles < 100 µm). We performed espresso extractions for a range of median particle sizes and systematically varying the share of fines by adding sieved fines to the coffee grounds. Dynamic beverage weights, extraction percentage, extraction time and dynamic headspace PTR-MS (proton-transfer mass spectrometer) analysis and sensory evaluation of the resulting brews were measured. We show that the share of fines plays a key role in the espresso extraction flow rate. An increase of share of fines decreases coffee bed permeability, leads to reduced flow rates and longer extraction times. A statistical model using partial least squares regression of the particle size distributions of coffee grounds confirms that fines decrease the coffee bed permeability. The PTR-MS analysis shows a non-linear increase of aroma compounds in the cup with increasing extraction yield. Our hypothesis is that both extraction efficiency and post-extraction evaporative losses of aroma compounds influence the final aroma compound concentrations in the cup.
The impact of COVID-19 lockdowns on mental health patient populations in the United States
Authors: Ferwana Ibtihal , Varshney Lav R.
Published: March 2024

During the start of the COVID-19 pandemic in 2020, lockdowns and movement restrictions were thought to negatively impact population mental health, since depression and anxiety symptoms were frequently reported. This study investigates the effect of COVID-19 mitigation measures on mental health across the United States, at county and state levels using difference-in-differences analysis. It examines the effect on mental health facility usage and the prevalence of mental illnesses, drawing on large-scale medical claims data for mental health patients joined with publicly available state- and county-specific COVID-19 cases and lockdown information. For consistency, the main focus is on two types of social distancing policies, stay-at-home and school closure orders. Results show that lockdown has significantly and causally increased the usage of mental health facilities in regions with lockdowns in comparison to regions without such lockdowns. Particularly, resource usage increased by 18% in regions with a lockdown compared to 1% decline in regions without a lockdown. Also, female populations have been exposed to a larger lockdown effect on their mental health. Diagnosis of panic disorders and reaction to severe stress significantly increased by the lockdown. Mental health was more sensitive to lockdowns than to the presence of the pandemic itself. The effects of the lockdown increased over an extended time to the end of December 2020.
Electrochemical and hot corrosion behaviour of annealed AlCoCrFeNi HEA coating over steel
Authors: Radhika N. , Noble Niveditha , Adediran Adeolu Adesoji
Published: March 2024

The ability to endure extreme corrosion in challenging environments is reduced in stainless steel. This can be addressed by appropriate surface modification techniques to redefine the surface with the required properties. The characteristics of the atmospheric plasma sprayed AlCoCrFeNi High Entropy Alloy (HEA) on SS316l are presented in this study. The coating characterisation revealed uniform coating with homogeneous deposition of gas-atomized AlCoCrFeNi HEA spanning for 150 µm. The coated substrates were further annealed for 2 h at 400 °C, 550 °C, 700 °C and 850 °C and the annealing at 550 °C offered enhanced microstructure. Annealing the coated sample at 550 °C offered a 46% improvement in microhardness against the uncoated sample post-annealing. The electrochemical corrosion tests showcased improved corrosion resistance after annealing through the formation of a protective oxide layer and the influence of HEA. Hot corrosion tests at 900 °C resulted in 10.1%, 8.49%, and 10.36% improved corrosion resistance for the coated sample annealed at 550 °C than the coated sample pre annealing and 44.09%, 44.25%, and 42.09% than the uncoated sample pre annealing under three salt mixtures respectively. The microstructural analysis examines various corrosion modes and verifies the presence and formation of protective oxide layers.
Internet addiction and its relationship with food choice motives and the risk of eating disorders among young adults in Malaysia
Authors: Mohammad Johari Muhammad Haziq , Tan Seok Tyug
Published: March 2024

The COVID-19 lockdown measures have dramatically altered the daily routines of young adults. Therefore, this study aims to elucidate the relationships between internet addiction, food choice motives and the risk of eating disorders in young adults during the transition to the endemic phase of COVID-19. The Internet Addiction Test was utilised to evaluate the presence and severity of internet addiction among young adults. The Food Choice Questionnaire was employed to assess the food choice motives of young adults, while the risk of eating disorders was determined using the Eating Attitude Test-26. The relationships between internet addiction, food choice motives, and the risk of eating disorders were assessed using model 4 of the PROCESS macro for SPSS. The findings indicated that 29.0% of young adults experienced moderate-to-severe internet addiction, whereas 32.6% were at risk of eating disorders. Young adults were highly valued for the price, sensory appeal, and mood when deciding food choices. The relationship between internet addiction and the risk of eating disorders was partially mediated by convenience (b = − 0.211, SE = 0.140, − 0.548 to − 0.016) and familiarity (b = 0.219, SE = 0.122, 0.019 to 0.494). A significant direct effect was also observed between internet addiction and the risk of eating disorders (B = 0.793, p = 0.017). There is an urgent need to implement intervention strategies aimed at reducing problematic internet use, promoting healthier food choices, and fostering healthy eating habits among young adults.
Phase envelopes in reservoir fill analysis: Two contrasting scenarios
Authors: Arouri Khaled R. , Herrera Carlos G.
Published: March 2024

Phase envelopes are routinely employed by reservoir engineers for fluid characterisation. These envelopes are controlled by reservoir fluid composition, pressure and temperature. As a result of increasing source-rock maturation, fluids with decreasing molecular weights and densities and increasing gas-to-oil ratios (and hence different phase envelopes) are generated, which are thus linked to fluid history. In addition to their importance for exploration, charge models can play a key role in constraining reservoir models and optimising field development, particularly when pressure–volume-temperature (PVT) data are properly integrated with fluid geochemistry. Two contrasting scenarios of fluid phase evolution from two different fields are presented, and their relations to charge analysis and reservoir models are discussed. The first example discusses the identification, based on hydrocarbon geochemistry complemented by overlapping modeled phase envelopes, of compartmentalised filling cycles in what was initially considered a single oil-rimmed gas accumulation. The second example presents an opposite scenario where two wet gas accumulations 20-km apart laterally and 400-feet average depth difference appear to represent a single more-expansive accumulation spread over areas of variable PVT conditions and reservoir qualities. The wet gas across both accumulations is characterised by a continuous phase evolution pattern that shrinks systematically (cricondentherm shifts to lower temperature and cricondenbar to lower pressure), suggestive of phase fractionation of a charge of single maturity. The proposed gas distribution model represents a discovery of a hybrid conventional and unconventional (tight sand) system, with potential for basin-centered gas. These findings provided better understanding of observed and projected fluids, impacting the development and completion plans by locating new gas producers. A recent well drilled midway between the two accumulations indeed tested wet gas, confirming fluid connectivity. Future work will attempt to link the gas distribution model with seismic attributes.
Prevalence of prehospital pain and pain assessment difference between patients and paramedics: a prospective cross-sectional observational study
Authors: Häske David , Dorau Wolfgang , Eppler Fabian , Heinemann Niklas , Metzger Florian , Schempf Benjamin
Published: March 2024

Adequate analgesia is one of the most important interventions in emergency medicine. However, studies suggest that many patients are undertreated for pain. There can be many reasons why patients assess their pain differently to the paramedics. This study aimed to assess the differences in pain ratings between patients and paramedics and factors influencing them in prehospital emergencies. This prospective cross-sectional observational study included patients treated and transported by paramedics or paramedics and emergency physicians of the German Red Cross in Reutlingen, Germany. This study included 6,365 patients. The prevalence of pain was 49.7%. Among patients with a self-reported numerical rating scale (NRS) > 0, the mean patient pain rating was NRS 4.2 ± 2.7, while the mean paramedic pain rating was NRS 3.6 ± 2.4 (p < 0.001). Approximately 11.8% (n = 751) of patients reported subjectively unbearable pain. Patients reported a mean NRS of 7.7 ± 1.8 for unbearable pain, but a mean NRS of 3.3 ± 2.0 for bearable pain (p < 0.001). The difference in pain ratings between patients and paramedics increased with pain severity. Univariate analysis showed that there were no gender differences, but the difference in pain rating was influenced by patient age (p < 0.001) and paramedic age (p = 0.042). The differences in pain ratings were particularly pronounced for abdominal diseases (p < 0.001) and trauma (p < 0.001). There is a difference in pain ratings between patients and paramedics, which increases with pain severity and appears to be associated with the patient’s age and the paramedic’s age. To determine the desire and need for analgesics, the question about unbearable pain is a good addition to the NRS.
Classifying autism in a clinical population based on motion synchrony: a proof-of-concept study using real-life diagnostic interviews
Authors: Koehler Jana Christina , Dong Mark Sen , Song Da-Yea , Bong Guiyoung , Koutsouleris Nikolaos , Yoo Heejeong , Falter-Wagner Christine M.
Published: March 2024

Predictive modeling strategies are increasingly studied as a means to overcome clinical bottlenecks in the diagnostic classification of autism spectrum disorder. However, while some findings are promising in the light of diagnostic marker research, many of these approaches lack the scalability for adequate and effective translation to everyday clinical practice. In this study, our aim was to explore the use of objective computer vision video analysis of real-world autism diagnostic interviews in a clinical sample of children and young individuals in the transition to adulthood to predict diagnosis. Specifically, we trained a support vector machine learning model on interpersonal synchrony data recorded in Autism Diagnostic Observation Schedule (ADOS-2) interviews of patient-clinician dyads. Our model was able to classify dyads involving an autistic patient (n = 56) with a balanced accuracy of 63.4% against dyads including a patient with other psychiatric diagnoses (n = 38). Further analyses revealed no significant associations between our classification metrics with clinical ratings. We argue that, given the above-chance performance of our classifier in a highly heterogeneous sample both in age and diagnosis, with few adjustments this highly scalable approach presents a viable route for future diagnostic marker research in autism.
Comparison of elasticity changes in the paraspinal muscles of adolescent patients with scoliosis treated with surgery and bracing
Authors: Lim Hyun Ji , Yoon Haesung , Kim Jisoo , Han Kyunghwa , So Yuri , Park Mincheol , Park Kun-Bo , Lee Mi-Jung
Published: March 2024

Scoliosis is a three-dimensional spinal deformity, and paraspinal muscles play an important role as stabilizers of the spinal curve. In this prospective study, we compared elasticity changes in the paraspinal muscles of adolescent patients with scoliosis after surgery or bracing. Elasticity was measured on the concave and convex sides of the paraspinal muscles at the apex of the curve at the beginning of treatment and 6 and 12 months after treatment. Twenty-six patients with correction surgery (n = 15) or bracing (n = 11) were included. At initial evaluation, the Cobb angle was larger in the surgery group (72.3 ± 20.2° in surgery vs. 30.6 ± 5.1° in brace, p < 0.001). The estimated mean elasticity value of the paraspinal muscles was lower in the surgery group at baseline on the convex side (15.8 vs. 22.8 kPa, p = 0.037) and 6 months on both the concave (12.1 vs. 22.7 kPa, p = 0.004) and convex (13.4 vs. 23.8 kPa, p = 0.005) sides. There was a significant stiffness decrease from baseline to 6 months on the concave side in the surgery group (5.9 kPa, p = 0.025). However, the elasticity change recovered at 12 months without significant differences between the two groups.
Essential role of local antibody distribution in mediating bone-resorbing effects
Authors: Nurkkala-Karlsson Merja , Lagerquist Marie K. , Gupta Priti , Ohlsson Claes , Mellström Dan , Engdahl Cecilia
Published: March 2024

The link between antibodies and bone mass is debated. Activated IgG, which interacts directly with Fc gamma receptors, stimulates osteoclastogenesis in vitro, and local injection in immune-activated mice leads to bone loss. Multiple myeloma patients with high serum IgG levels have induced osteoclast activation and display bone loss. In addition, bone loss has been linked to serum autoantibodies in autoimmune diseases, including anti-citrullinated protein antibodies (ACPA) in individuals with rheumatoid arthritis (RA). Whether serum IgG or autoantibodies regulate bone mass under healthy conditions is poorly studied. In elderly men, neither serum levels of polyclonal IgG nor autoantibody were associated with areal bone mineral density in the MrOS Sweden study. Repetitive systemic injections of high-dose polyclonal IgG complexes in mice did not exert any discernible impact on bone mineral density. However, repetitive local intra-articular injection of the same IgG complexes led to a localized reduction of trabecular bone density. These results indicate antibodies may only impact bone density when close to the bone, such as within the synovial joint.
Diversity, community structure, and abundance of nirS-type denitrifying bacteria on suspended particulate matter in coastal high-altitude aquaculture pond water
Authors: Chunyi Kuang , Wei Sun , Mingken Wei , Chunyu Xia , Changxiu Li
Published: March 2024

Denitrifying bacteria harboring the nitrate reductase S (nirS) gene convert active nitrogen into molecular nitrogen, and alleviate eutrophication in aquaculture water. Suspended particulate matter (SPM) is an important component of aquaculture water and a carrier for denitrification. SPM with different particle sizes were collected from a coastal high-altitude aquaculture pond in Maoming City, China. Diversity, community structure, abundance of nirS-type denitrifying bacteria on SPM and environmental influencing factors were studied using high-throughput sequencing, fluorescence quantitative PCR, and statistical analysis. Pseudomonas, Halomonas, and Wenzhouxiangella were the dominant genera of nirS-type denitrifying bacteria on SPM from the ponds. Network analysis revealed Pseudomonas and Halomonas as the key genera involved in the interaction of nirS-type denitrifying bacteria on SPM in the ponds. qPCR indicated a trend toward greater nirS gene abundance in progressively larger SPM. Dissolved oxygen, pH, temperature, and SPM particle size were the main environmental factors influencing changes in the nirS-type denitrifying bacterial community on SPM in coastal high-altitude aquaculture pond water. These findings increase our understanding of the microbiology of nitrogen cycle processes in aquaculture ecosystem, and will help optimize aquatic tailwater treatment strategies.
Blockchain based medical image encryption using Arnold’s cat map in a cloud environment
Authors: Inam Saba , Kanwal Shamsa , Firdous Rabia , Hajjej Fahima
Published: March 2024

Improved software for processing medical images has inspired tremendous interest in modern medicine in recent years. Modern healthcare equipment generates huge amounts of data, such as scanned medical images and computerized patient information, which must be secured for future use. Diversity in the healthcare industry, namely in the form of medical data, is one of the largest challenges for researchers. Cloud environment and the Block chain technology have both demonstrated their own use. The purpose of this study is to combine both technologies for safe and secure transaction. Storing or sending medical data through public clouds exposes information into potential eavesdropping, data breaches and unauthorized access. Encrypting data before transmission is crucial to mitigate these security risks. As a result, a Blockchain based Chaotic Arnold’s cat map Encryption Scheme (BCAES) is proposed in this paper. The BCAES first encrypts the image using Arnold’s cat map encryption scheme and then sends the encrypted image into Cloud Server and stores the signed document of plain image into blockchain. As blockchain is often considered more secure due to its distributed nature and consensus mechanism, data receiver will ensure data integrity and authenticity of image after decryption using signed document stored into the blockchain. Various analysis techniques have been used to examine the proposed scheme. The results of analysis like key sensitivity analysis, key space analysis, Information Entropy, histogram correlation of adjacent pixels, Number of Pixel Change Rate, Peak Signal Noise Ratio, Unified Average Changing Intensity, and similarity analysis like Mean Square Error, and Structural Similarity Index Measure illustrated that our proposed scheme is an efficient encryption scheme as compared to some recent literature. Our current achievements surpass all previous endeavors, setting a new standard of excellence.
Synthetic polyploidization induces enhanced phytochemical profile and biological activities in Thymus vulgaris L. essential oil
Authors: Gupta Neha , Bhattacharya Soham , Dutta Adrish , Tauchen Jan , Landa Přemysl , Urbanová Klára , Houdková Markéta , Fernández-Cusimamani Eloy , Leuner Olga
Published: March 2024

Essential oil from Thymus vulgaris L. has valuable therapeutic potential that is highly desired in pharmaceutical, food, and cosmetic industries. Considering these advantages and the rising market demand, induced polyploids were obtained using oryzalin to enhance essential oil yield. However, their therapeutic values were unexplored. So, this study aims to assess the phytochemical content, and antimicrobial, antioxidant, and anti-inflammatory activities of tetraploid and diploid thyme essential oils. Induced tetraploids had 41.11% higher essential oil yield with enhanced thymol and γ-terpinene content than diploid. Tetraploids exhibited higher antibacterial activity against all tested microorganisms. Similarly, in DPPH radical scavenging assay tetraploid essential oil was more potent with half-maximal inhibitory doses (IC50) of 180.03 µg/mL (40.05 µg TE/mg) than diploid with IC50 > 512 µg/mL (12.68 µg TE/mg). Tetraploids exhibited more effective inhibition of in vitro catalytic activity of pro-inflammatory enzyme cyclooxygenase-2 (COX-2) than diploids at 50 µg/mL concentration. Furthermore, molecular docking revealed higher binding affinity of thymol and γ-terpinene towards tested protein receptors, which explained enhanced bioactivity of tetraploid essential oil. In conclusion, these results suggest that synthetic polyploidization using oryzalin could effectively enhance the quality and quantity of secondary metabolites and can develop more efficient essential oil-based commercial products using this induced genotype.
Male–female disparity in clinical features and significance of mild vertebral fractures in community-dwelling residents aged 50 and over
Authors: Ikegami Shota , Uehara Masashi , Tokida Ryosuke , Nishimura Hikaru , Sakai Noriko , Horiuchi Hiroshi , Kato Hiroyuki , Takahashi Jun
Published: March 2024

This investigation examined the clinical implications of mild vertebral fractures in older community-dwelling residents. Focusing on the locomotion health of older individuals, the earlier reported Obuse study enrolled 415 randomly sampled Japanese residents aged between 50 and 89 years, 411 of whom underwent X-ray evaluations for pre-existing vertebral fractures. A blinded assessment of vertebral fractures based on Genant’s criteria was conducted on the T5-L5 spine for rating on a severity scale. Grade 1 mild fractures were not linked to age in males, but increased with aging in females. Female participants had fewer Grade 1 and 2 fractures (P = 0.003 and 0.035, respectively) but more Grade 3 fractures (P = 0.013) than did males independently of age (Grade 1, 2, and 3: 25%, 16%, and 9% in females and 40%, 22%, and 6% in males, respectively). Weak negative correlations were observed between the number of fractures and bone mineral density in females for all fracture grades (Spearman’s rho: 0.23 to 0.36, P < 0.05). Our study showed that Grade 1 mild vertebral fractures in males lacked pathological significance, while in females they potentially indicated fragility fractures and were related to poor lumbopelvic alignment.
Connectivity mapping-based identification of pharmacological inhibitor targeting HDAC6 in aggressive pancreatic ductal adenocarcinoma
Authors: Atri Pranita , Shah Ashu , Natarajan Gopalakrishnan , Rachagani Satyanarayana , Rauth Sanchita , Ganguly Koelina , Carmicheal Joseph , Ghersi Dario , Cox Jesse L. , Smith Lynette M. , Jain Maneesh , Kumar Sushil , Ponnusamy Moorthy P. , Seshacharyulu Parthasarathy , Batra Surinder K.
Published: March 2024

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to limited therapeutic options and expensive/burdensome drug discovery processes. Utilizing genomic-data-driven Connectivity Mapping (CMAP) to identify a drug closer to real-world PC targeting may improve pancreatic cancer (PC) patient outcomes. Initially, we mapped CMAP data to gene expression from 106 PC patients, identifying nine negatively connected drugs. These drugs were further narrowed down using a similar analysis for PC cell lines, human tumoroids, and patient-derived xenografts datasets, where ISOX emerged as the most potent agent to target PC. We used human and mouse syngeneic PC cells, human and mouse tumoroids, and in vivo mice to assess the ability of ISOX alone and in combination with 5FU to inhibit tumor growth. Global transcriptomic and pathway analysis of the ISOX-LINCS signature identified HDAC 6/cMyc as the target axis for ISOX. Specifically, we discovered that genetic and pharmacological targeting of HDAC 6 affected non-histone protein cMyc acetylation, leading to cMyc instability, thereby disrupting PC growth and metastasis by affecting cancer stemness. Finally, KrasG12D harboring tumoroids and mice responded effectively against ISOX and 5FU treatment by enhancing survival and controlling metastasis incidence. Overall, our data validate ISOX as a new drug to treat advanced PC patients without toxicity to normal cells. Our study supports the clinical utility of ISOX along with 5FU in future PC clinical trials.
Exploring the limitations of mitochondrial dye as a genuine horizontal mitochondrial transfer surrogate
Authors: Chen Chuanfang , Li Haige , Zhang Jia , Cheng Shih-Chin
Published: March 2024

Rosamine-based mitochondrial dyes, such as Mitotracker Red, have commonly been employed to visualize mitochondrial localization within cells due to their preferential accumulation in organelles with membrane potential. Consequently, Mitotracker Red has often served as a surrogate indicator for tracking mitochondrial movement between neighboring cells. However, it is important to note that the presence of membrane potential in the cell membrane and other organelles may lead to the non-specific partial enrichment of Mitotracker Red in locations other than mitochondria. This study comprehensively investigates the reliability of mitochondrial dye as a marker for studying horizontal mitochondrial transfer (HMT). By meticulous replicating of previous experiments and comparing the efficiency of mitochondrial dye transfer with that of mito-targeted GFP, our findings confirm that HMT occurs at significantly lower efficiency than previously indicated by Mitotracker dye. Subsequent experiments involving mitochondria-deficient cells robustly demonstrates the non-specificity of mitochondrial dye as indicator for mitochondria. We advocate for a thorough reevaluation of existing literature in this field and propose exploration of alternative techniques to enhance the investigation of HMT. By addressing these pivotal aspects, we can advance our understanding of cellular dynamics and pave the way for future explorations in this captivating field.
SAM68 directs STING signaling to apoptosis in macrophages
Authors: van der Horst Demi , Kurmasheva Naziia , Marqvorsen Mikkel H. S. , Assil Sonia , Rahimic Anna H. F. , Kollmann Christoph F. , Silva da Costa Leandro , Wu Qi , Zhao Jian , Cesari Eleonora , Iversen Marie B. , Ren Fanghui , Jensen Trine I. , Narita Ryo , Schack Vivien R. , Zhang Bao-cun , Bak Rasmus O. , Sette Claudio , Fenton Robert A. , Mikkelsen Jacob G. , Paludan Søren R. , Olagnier David
Published: March 2024

DNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription. By intersecting four mass spectrometry datasets, we identify SAM68 as crucial for the induction of apoptosis downstream of STING activation. SAM68 is essential for the full activation of apoptosis. Still, it is not required for STING-mediated activation of IFN expression or activation of NF-κB. Mechanistic studies reveal that protein trafficking is required and involves SAM68 recruitment to STING upon activation, with the two proteins associating at the Golgi or a post-Golgi compartment. Collectively, our work identifies SAM68 as a STING-interacting protein enabling induction of apoptosis through this DNA-activated innate immune pathway.
Efficient retrosynthetic planning with MCTS exploration enhanced A* search
Authors: Zhao Dengwei , Tu Shikui , Xu Lei
Published: March 2024

Retrosynthetic planning, which aims to identify synthetic pathways for target molecules from starting materials, is a fundamental problem in synthetic chemistry. Computer-aided retrosynthesis has made significant progress, in which heuristic search algorithms, including Monte Carlo Tree Search (MCTS) and A*search, have played a crucial role. However, unreliable guiding heuristics often cause search failure due to insufficient exploration. Conversely, excessive exploration also prevents the search from reaching the optimal solution. In this paper, MCTS exploration enhanced A*(MEEA*) search is proposed to incorporate the exploratory behavior of MCTS into A*by providing a look-ahead search. Path consistency is adopted as a regularization to improve the generalization performance of heuristics. Extensive experimental results on 10 molecule datasets demonstrate the effectiveness of MEEA*. Especially, on the widely used United States Patent and Trademark Office (USPTO) benchmark, MEEA*achieves a 100.0% success rate. Moreover, for natural products, MEEA*successfully identifies bio-retrosynthetic pathways for 97.68% test compounds.
Hydrological drought forecasts using precipitation data depend on catchment properties and human activities
Authors: Sutanto Samuel Jonson , Syaehuddin Wahdan Achmad , de Graaf Inge
Published: March 2024

Hydrological Drought Early Warning Systems play a crucial role in effective drought planning and management, as the impacts of drought are more closely associated with hydrological droughts than meteorological ones. However, current systems primarily focus on meteorological drought forecasts due to the limited access to hydrological data. Here we assess the feasibility of forecasting drought in streamflow and groundwater by solely using precipitation data. The results demonstrate that meteorological drought forecasts derived from the Standardized Precipitation Index with 6-month accumulation periods and various lag times hold the potential to predict streamflow and groundwater droughts. This study also highlights the importance of catchment properties in hydrological drought predictions. Our findings present an opportunity for developing hydrological drought early warning system globally to reach the goal of the Sendai framework for disaster risk reduction by 2030 and support the initiative of early warnings for all.
Actuation of microstructures with spin-current volume effect
Authors: Huang Yi-Te , Suzuki Kenta , Arisawa Hiroki , Kikkawa Takashi , Saitoh Eiji , Ono Takahito
Published: March 2024

Microactuators are essential for advances in micro-optics, ultrasonic transducers and microsensors, and there is a growing demand for miniaturization and improved power. Here we demonstrate the actuation of micromechanical structures based on spin-current volume effect using an amorphous magnetic film of TbFeCo with volume magnetostriction. A 2 mm-diameter circular polyimide diaphragm coated with thin TbFeCo/non-magnetic metal films is prepared as the micromechanical structure. When an alternating charge current flows through the TbFeCo/non-magnetic metal films on the diaphragm under an external magnetic field orthogonal to the charge current, an alternating spin-current flows in the non-magnetic metal film due to the spin-Hall effect. In the spin-current volume effect, the spin-current transports angular momentum from the non-magnetic metal to TbFeCo film, and the spin-transfer torque modulates the magnetization fluctuation of the TbFeCo film, causing the diaphragm to vibrate due to spin-lattice coupling. The power density of the TbFeCo/Pt films actuator is larger than 1.17 × 106 W m−3at 20 mA charge current under 7.2 kOe magnetic field. This value is much higher than that of various existing film-type microactuators. This spin-current volume effect is effective as a new actuation mechanism for microactuators used in micro-optical systems, acoustic diagnostic equipment, and micro-fluidic systems etc.