bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Groundnut as Preceding Crop Reduce Fertilizer Requirement to the Succeeding Blackgram?-Results of Field Investigation
Authors: Harisudan C. , Veeramani P. , Allwin L. , Sathiya K. , Sivagamy K. , Karunakaran V.V. , Jayakumar J.
Published: June 2024

Background: Intensive legume cropping system enhances the soil productivity and reduce the dependance on exterior inputs as legumes are well known for nitrogen (N) fixation by biological means. In addition, inorganic fertilizers, together with the integrated and careful use of FYM, could be an efficient option for increasing the productivity of the legume - legume cropping system. The common use of fertilizer and organics has been shown to have a synergistic effect on crop productivity, while simultaneously improving soil fertility. The residual effects of organic manures applied to previous crops may be available to subsequent crops. As a result, this experiment was designed to shed information on the usage of integrated nutrients from organic and inorganic sources on leguminous groundnut and the residual influence on subsequent blackgram. Methods: During 2018-19, 2019-20 and 2020-21, a field experiment was undertaken at Regional Research Station, Tamil Nadu Agricultural University, Vridhachalam to investigate the effect of integrated nutrient management on the groundnut-blackgram cropping sequence. Four nutrient combinations for groundnut were tested in a randomized block design and the residual effect on productivity of succeeding blackgram was investigated using four fertilizer levels in a split plot design. Result: The application of 125% RDF + FYM @ 12.5 t ha-1 to groundnut increased growth, yield, quality, economics and soil properties, while the residual effect to succeeding blackgram resulted in significantly higher blackgram seed yield and other important parameters, which was followed by the application of 75% RDF. Among the various levels of fertilizers applied to blackgram, 75% RDF produced the highest blackgram seed yield, economics and soil characteristics compared to the other three levels.
Lecciones para la PCSD tras la Guerra en Ucrania
Authors: Abad Gracia
Published: June 2024

The evolution of the European Union, far from being linear, is undoubtedly a story of laudable advances and resounding setbacks. This uneven evolution is particularly visible in the area of security and defence. Thus, if on the one hand the Treaty of Amsterdam was followed by years of great advances such as those that materialised in Saint Malo, Helsinki, Cologne, Santa Maria de Feira and Lisbon, then the triple shock of the Iraq War, the financial crisis and the COVID 19 pandemic led to a period of deadlock and a substantial darkening of the outlook. However, this situation would not be in doubt forever because a new war, in Ukraine, perceived as a fundamental strategic change that challenged the interests and values of the Union, was to awaken Europeans and generate a new momentum in terms of security and defence, allowing for a more determined search for greater strategic autonomy with all that this entails. This momentum is further boosted by the fact that the EU's easternmost member states, traditionally more reticent in this area, being the most affected by the renewed Russian threat, may start to be much less so. In these conditions, the enlargement debate is even reopened, opening the door to states that, if they are able to meet the preceptive requirements for accession, could in some cases constitute an undoubted asset for the security and defence of the EU as a whole.
Bounded Number Theory: A Study on the Negation of Infinite Numbers in Parts or Completely
Authors: Cardoso Carlos Eduardo Ramos
Published: June 2024

The theory of limited numbers says that the number is not infinite, that is, the number is limited in parts or completely. To reach a conclusion about the limited number, one must understand the meaning of mathematics and varied spaces, therefore, one must understand that mathematics and spaces interact. Mathematics has the function of accurately describing the world, where numbers represent elements or facts that rationally belong to space, and spaces have different intensity of specific physical concepts in each space; therefore, there is no infinite element or fact due to the differences in the intensities of specific physical concepts in spaces that do not allow the fact or fact in all spaces.
Beneficial Plant-Microbe Interactions and Stress Tolerance in Maize
Authors: Burlakoti Saroj , Devkota Ananta R , Poudyal Shital , Kaundal Amita
Published: June 2024

Beneficial microbes are crucial for improving crop adaptation and growth under vari-ous stresses. They enhance nutrient uptake, improve plant immune responses, and help plants tolerate stresses like drought, salinity, and heat. The yield potential of any crop is significantly influenced by its associated microbiomes and their potential to im-prove growth under different stressful environments. Therefore, it’s crucial and excit-ing to understand the mechanisms of plant-microbe interactions. Maize (Zea mays L.) is one of the primary staple foods worldwide, in addition to wheat and rice. Maize is also an industrial crop globally, contributing 83% of its production for use in feed, starch, and biofuel industries. Maize requires significant nitrogen fertilization to achieve opti-mal growth and yield. Maize plants are highly susceptible to heat, salinity, and drought stresses and require innovative methods to mitigate the harmful effects of environmental stresses and reduce the use of chemical fertilizers. This review summarizes our current understanding of the beneficial interactions between maize plants and specific microbes. These beneficial microbes improve plant resilience to stress and in-crease productivity. For example, they regulate electron transport, downregulate cata-ase, and upregulate antioxidants. We also review the roles of plant growth promoting rhizobacteria (PGPR) enhancing stress tolerance in maize. Additionally, we explore the application of these microbes in maize production and identify major knowledge gaps that need to be addressed to utilize the potential of beneficial microbes fully.
Astromineralogy of the Nearby Exoplanetary Systems I: A Comparative Analysis of the Stellar and the Averaged Solar Mg/Si and Fe/Si Molar Ratios
Authors: Futó Péter , Gucsik Arnold , Simonia Irakli , Kajati György
Published: June 2024

This study was based on the corresponding elemental abundances of carbonaceous - chondrites and the Solar photospheric elemental abundances [1]. The comparative analysis between the average magnesium, silicon and iron abundances of the Solar System and the abundances of these elements in potential nearby planetary systems was based on the Mg, Si and Fe abundances of host stars, which are in the Galactic thin disk within 25 parsecs distance from the Sun. The stellar abundance data had been taken from the Hypatia Catalog, which contains high precision data of chemical elements. We show that in general there are no significant differences between the molar Mg/Si and Fe/Si ratios of the most examined stars and the corresponding elemental ratios of the Solar System. However, the comparative study also shows that a significant fraction of the nearby extrasolar terrestrial planets may have higher bulk Mg/Si ratio than Solar, but the Solar Fe/Si ratio can relatively be frequent. We conclude that the medium - sized metallic cores can relatively be common in the rocky planetary interiors, while the mantle mineralogy for most of the rocky exoplanets in the Solar neighborhood may differ from that of Earth.
Quantum Mechanics Characterization of Non-Covalent Interaction in Nucleotides Fragments
Authors: Tarek Ibrahim Mayar , Wait Elizabeth , Ren Pengyu
Published: June 2024

Accurate calculation of non-covalent interaction energies in nucleotides is crucial for understanding the driving forces governing nucleic acid structures and functions, as well as developing advanced molecular mechanics forcefields or machine learning potentials tailored to nucleic acids. Here, we dissect the nucleotides’ structure into three main constituents: nucleobases (A, G, C, T, and U), sugar moieties (ribose and deoxyribose), and phosphate group. The interactions among these fragments and between fragment and water were analyzed. Different quantum mechanical methods were compared for their accuracy in captuing the interaction energy. The non-covalent interaction energy was decomposed into electrostatics, exchange-repulsion, dispersion, and induction using two ab-initio methods: Symmetry-Adapted Perturbation Theory (SAPT) and Absolutely Localized Molecular Orbitals (ALMO). These caculations provide the benchmark for different QM methods while providing valuable understanding of the roles of various interamolecular forces in hydrogen bonding and aromatic stacking.
ANALYSIS OF THE ONCOLOGICAL STATE AMONG THE LAW ENFORCEMENT AUTHORITIES OF THE OF SAKHA (YAKUTIA) IN THE 2019-2021
Authors:   Medical Unit of the Ministry of internal Affairs of Russia for the Sakha Respublic (Yakutia), DOLINSKAYA ELVIRA A.
Published: June 2024

Abstract. Introduction. Cancer is the third most common disease type among all. It is one of the leading causes of death, disability and premature disability in the law enforcement system. Aim. The purpose of the study is identifying main forms of cancer, gender and age characteristics of oncological diseases, analysis of the oncological situation among law enforcement officers to determine suitability for service. Material and methods. We performed a simple multivariate comparative analysis of law enforcement officers' cancer morbidity data, individual clinical cases of patients according to hospital and military medical commission statistical reporting materials for 2019-2021. Results and discussion. All nosological forms of the diseases require specialized medical care. Cancer morbidity leads to long-term disability and, as a rule, to ineligibility for military service in the law enforcement system. Conclusion. Male patients of working age suffer from cancer more often. The age of oncopathology is quite wide and varies from 25 to 74 years among patients assigned to the Medical-Sanitary Unit. There is no direct connection of patients' oncopathology with the kind and type of the patient's activity. At timely detection the outcome of the disease for the patient in most cases remains favorable. The mortality from oncological pathology in 2019 - 2022 reaches 7.5 cases per 10,000 population. For the purpose of timely diagnosis and treatment it is necessary to develop the primary oncological branch in departments of outpatients' clinics, to conduct annual analysis of oncological morbidity, estimating the number of patients recognized ineligible for service in the internal affairs bodies.
Causes of paroxysmal dyspnea in patients with stable coronary artery disease
Authors: Yarmedova S. F. , Yavelov I. S. , Drapkina O. M.
Published: June 2024

Aim. To study possible causes of dyspnea in patients with stable coronary artery disease (CAD).

Material and methods. 101 patients with stable CAD and paroxysmal dyspnea who underwent inpatient treatment in the cardiology department were included in the observational study. The following parameters were analyzed: presence and severity of dyspnea, angina pectoris, chronic heart failure (CHF), anxiety and/or depression, results of physical examination, electrocardiography,laboratory tests (levels of high sensitive cardiac troponin, natriuretic peptide and thyroid-s timulating hormone in the blood), a 6 minute walk test, multispiral computed tomography or chest X-ray, Holter monitorechocardiography, stress echocardiography with a treadmill load, spirometry with a bronchodilation test, as well as coronary angiography, which was performed in the detection of myocardial ischemia were.

Results. Transient myocardial ischemia as a cause of dyspnea was diagnosed in 36 patients (35.6%). At the same time, chest pain during stress echocardiography was noted only in 5% of cases. In addition to myocardial ischemia, the following possible causes of dyspnea were found: CHF with preserved left ventricular ejection fraction (EF) in 76 patients (75.2%), obesity — in 34 (33.7%), anxiety — in 33 (32.7%), valvular pathology — in 28 (27.7%), pulmonary ventilation disorders — in 21 (20.8%), depression — in 20 (19.9%), cardiac rhythm and conduction disorders — in 9 (8,9%), thyroid dysfunction — in 7 (6.9%), CHF with mildly reduced EF — in 7 (6.9%), CHF with reduced EF — in 2 (2.0%), anaemia — in 2 (2.0%). The potential cause of dyspnea was not established in 2 patients (2.0%). One cause of dyspnea was diagnosed in 8.9%, a combination of two causes — in 38.6%, three — in 25.7%, four — in 15.8%, five — in 6.9%, six causes — in 1% of participants. Dyspnea commonly was associated with transient myocardial ischemia combined with CHF with preserved EF (17%), as well as CHF with preserved EF and valvular pathology (13.9%).

Conclusion. The obtained results confirm the variety of possible causes of dyspnea in patients with stable CAD, as well as the fact that transient myocardial ischemia is not the most common cause of dyspnea in this category of patients and in many cases is combined with other disorders accompanied by similar symptoms.
Enhanced Backpropagation Neural Network Approach for High Precision Fertilization Method in Greenhouse Vegetable Cultivation
Authors: Tang Ruipeng , Aridas Narendra Kumar , Talip Mohamad Sofian Abu , Tang Jian Rui
Published: June 2024

The traditional method of detecting crop nutrients is based on the direct chemical detection method in the laboratory, which causes great damage to crops. In order to solve the above problems, an precision fertilization method for greenhouse vegetables based on IM-BPNN(improved backpropagation neural network) algorithm is designed in this study. First, soil samples from the farm in china are selected. With the laboratory treatment, available phosphorus, available potassium, and alkaline nitrogen are extracted. These data are preprocessed by the z-score(zero-mean normalization) standardization method. Then, the BPNN(backpropagation neural network) algorithm is improved by being trained and combined with the characteristics of the dual particle swarm optimization algorithm. After that, the soil sample data are divided into training and test sets, and the model is established by setting parameters, weights, and network hierarchy. Finally, the NBTY(nutrient balance target yield) ,BPNN(backpropagation neural network) and IM-BPNN algorithm are used to calculate the amount of fertilizer. Compared with the NBTY algorithm, the available potassium, available phosphate, and alkaline hydrolysis nitrogen increases 35.78%, 20.93% and 18.08% in the reasonable range and increases 52.09%, 37.34%, and 20.59% in the best range. Compared with the BPNN algorithm, the available potassium, available phosphate, and alkaline hydrolysis nitrogen increases 15.47%, 12.06% and 9.82% in the reasonable range and increases 19.85%,18.98% and 11.35% in the best range. It shows that the IM-BPNN algorithm can more accurately determine the amount of fertilizer required by vegetables and avoid over-application, which can improve fertilizer utilization efficiency, reduce production costs, and improve the economic feasibility of agriculture.
COMMD10-deficiency in adipose tissue macrophages attenuates obesity and insulin resistance by boosting mitochondrial and antioxidant functions
Authors: Gluck Nathan , Ben-Shlomo Shani , Shrkihe Bander Abu , Radenbazarov Yulia , Erez Noam , Pasmanik-Chor Metsada , Shoham Ori , Abramovich Ifat , Gottlieb Eyal , Varol Chen
Published: June 2024

During obesity, adipose tissue macrophages (ATM) colonize the white adipose tissue (WAT), where they acquire metabolically activated phenotypes. Here, we demonstrate that COMMD10 is a key regulator of macrophage oxidative capacity in response to chronic caloric excess. Mice with COMMD10-deficiency targeted to macrophages fed high-fat-diet (HFD) gained less weight, showed improved serum metabolic indices, enhanced systemic and WAT insulin sensitivity, and reduced adipocyte hypertrophy and liver steatosis. COMMD10-deficient ATM exhibited increased oxidative respiration and mitochondrial membrane potential after short and long term HFD. These findings were recapitulated in COMMD10-deficient BM-derived macrophages and human THP1 monocyte-derived macrophages. Intracellular copper was elevated in COMMD10-deficient macrophages, and its chelation normalized their increased mitochondrial respiration. Both glucose and lipids fueled the increased oxidative respiration in COMMD10-deficient ATM, and they better adapted to oxidative stress by upregulating NRF2-dependent antioxidant transcriptional modules. Overall, COMMD10-deficiency in ATM safely augments mitochondrial energy production and improves obesity-associated metabolic derangements.
No Genetic Causal Association Between Human Papillomavirus and Lung Cancer Risk A Bidirectional Two-Sample Mendelian Randomization Analysis
Authors: 陈 仪卓 , Xu Ziqing , Zhang Zhouqi , Wang Xin , Dong Ming
Published: June 2024

This study systematically explores whether human papillomavirus (HPV) infection is causally related to lung cancer risk through a bidirectional Two-Sample Mendelian Randomization analysis. Using data from the International Lung Cancer Consortium (ILCCO) genome-wide association study dataset, comprising 11,348 lung cancer (LUCA) cases and 15,861 controls, we utilized genetic variants associated with the HPV E7 protein as instrumental variables. Our two-sample Mendelian Randomization analysis found no causal relationship between HPV infection and lung cancer (LUCA), including its subtypes squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD). Reverse analysis yielded similar results, indicating no significant causal link between LUCA and its subtypes and HPV infection. In conclusion, our findings do not support a genetic association between HPV infection and lung cancer.
Analysis of the CO2 Content in the PIM (Mangrove Information Center) Area in Pekalongan City, Central Java Province
Authors: Zainuri Muhammad , Ismanto Aris , Safinatunnajah Novia , Nasir Muhammad , Hadibarata Tony , Handoyo Gentur , Rifai Azis
Published: June 2024

Mangrove forests have an important ecological function as absorbing and storing carbon in efforts to mitigate global warming, overcome world climate change due to increased CO2 emissions, and reduce the impact of climate change. Carbon dioxide (CO2) acts as an indicator parameter for water and land activity, related to water-sea interactions and water productivity. The results of data processing show the concentration of CO2 in the Lagoon of the Pekalongan Regency, with the highest average and distribution values at several stations. Total organic carbon ranges between 1.12–13.67% the dissolve inorganic carbon ranges from 27.97 to 99.88 mg/L. CO2 content exceeding 20 mg/L can harm marine life and is an impact of global warming. In addition, sea water temperature varies along the station and is influenced by geographic location, land influence, and sea water mass. Station 3 has the lowest temperature, perhaps due to the influence of offshore sea water masses. This research illustrates the importance of managing mangrove ecosystems, measuring CO2 concentrations in waters, and understanding their impact on the marine environment.
Phosphorylation-mediated conformational switch regulates human SLFN11
Authors: Lammens Katja , Kugler Michael , Metzner Felix , Hopfner Karl-Peter
Published: June 2024

Human Schlafen 11 (SLFN11) serves as a predictive biomarker in cancer as it sensitizes cells to DNA damaging agents by irreversibly blocking stalled replication forks. SLFN11 further acts as an interferon-inducible antiviral restriction factor that targets translation in a codon-usage-dependent manner. However, the regulation of the SLFN11 functions and enzymatic activities remains enigmatic. Here, we present a structural and biochemical explanation for the regulation of SLFN11 by phosphorylation. A cryo-electron microscopy (cryo-EM) structure of the SLFN11 phosphomimetic mutant S753D revealed that it adopts a monomeric conformation, allowing ATP binding, yet loses its ability to bind single-stranded DNA (ssDNA). Cryo-EM structures of SLFN11 bound to tRNA-Leu and tRNA-Met give insights into tRNA binding and cleavage, as well as its regulation by phosphorylation at S219 and T230. Thus, the phosphorylation site S753 serves as a conformational switch, regulating SLFN11 dimerization, as well as ATP and ssDNA binding, while S219 and T230 regulate tRNA recognition and nuclease activity.
Assessing Risk of Interfacility Transport in Pregnant Patients due to Progression of Labor – Lessons from a Specialized Maternal-Fetal Transport Program
Authors: Lardaro Thomas , Balaji Adhitya , Kuhn Diane , Glober Nancy , Brent Christine M , Couturier Katherine , Breyre Amelia , Vaizer Julia , Hunter Benton R
Published: June 2024

Background
Pregnant laboring patients sometimes require interfacility transfer to a higher level of care. There is a paucity of evidence to inform when it is safe to transfer a laboring patient and when delivery may be too imminent to transfer.
Methods
This is a retrospective study of pregnant patients undergoing interfacility transfer with a specialized obstetric transport team deployed from a large Midwest regional healthcare system. The primary outcome was delivery prior to or within 1 hour of arrival at the receiving institution due to progression of labor. Data collected included basic demographics, vital signs, gravity, parity, gestational age, contraction frequency if contractions were present, and cervical dilation. We sought to define the association between these variables and the primary outcome to inform risk assessment for precipitous delivery among patients being considered for interfacility transfer.
Results
Of 370 pregnant patients for whom the specialized transfer team was requested, 11 (3%) met the primary outcome. Those with more advanced cervical dilation and those who did not have regular prenatal care were more likely to meet the criteria for the primary outcome. For every centimeter of cervical dilation, the odds of meeting the primary outcome increased 2.3-fold (95% CI 1.5 to 3.4).
Conclusions
We identify risk factors for early delivery among pregnant patients for whom an interfacility transfer was requested and describe patients who were high-risk for obstetric interfacility transport due to progression of labor. Our results can help inform risk assessments for the transfer of potentially high-risk laboring patients.
Geometry of the Visual Cortex With Applications to Image Inpainting and Enhancement
Authors: Ballerin Francesco , Grong Erlend
Published: June 2024

Equipping the rototranslation group SE(2) with a sub-Riemannian structure inspired by the visual cortex V1, we propose algorithms for image inpainting and enhancement based on hypoelliptic diffusion. We innovate on previous implementations of the methods by Citti, Sarti, and Boscain et al., by proposing an alternative that prevents fading and is capable of producing sharper results in a procedure that we call WaxOn-WaxOff. We also exploit the sub-Riemannian structure to define a completely new unsharp filter using SE(2), analogous to the classical unsharp filter for 2D image processing. We demonstrate our method on blood vessels enhancement in retinal scans.
Unusual cases of crescentic glomerulonephritis with normal renal function at diagnosis: a retrospective case series from a single center in Western China
Authors: Wu Xin , Zhang Ping , Wang Wei , Chen Shasha
Published: June 2024

Background. The aim of this study is to investigate the clinicopathologic characteristics, treatment and prognosis of crescentic glomerulonephritis (Crescentic GN) in patients with normal renal function at diagnosis, and compare to those with impaired renal function.
Methods. We conducted a retrospective review of patients with renal biopsy proven Crescentic GN at our center and divided them into normal eGFR group (eGFR≥60 ml/min/1.73 m2) and low eGFR group (eGFR <60 ml/min/1.73 m2). Clinical and renal pathological findings at diagnosis and renal outcomes were compared between the two groups using t test, Wilcoxon rank sum test or Kruskal-Wallis H test. Comparison of cumulative renal survival rates for ESRD was done by Kaplan-Meier curves and the log-rank test.
Results. From Jan 2010 to Dec 2021, 98 Crescentic GN patients with normal eGFR were included, in which clinicopathological diagnoses were LN(lupus nephritis) (60 cases, 66.77%), IgAN (IgA nephropathy) (9 cases, 10 %), HSPN (Henoch-Schnlein purpura nephritis) (4 cases, 15.6%) and AAV(ANCA-associated GN) (7 cases, 7.8%). Compared with the low eGFR group (n=300), the following characteristics were observed in the normal eGFR group: younger age (p<0.001), female predominance (p<0.001), longer time from onset to biopsy (p<0.001), lower hypertension rate (p<0.001), lower rate of oliguria(p<0.001), and anemia (p<0.001), lower levels of C3 (p<0.001), C4 (p<0.001) and Urine RBC (p<0.001), higher titers of ANA(p<0.001) and ds-DNA(p=0.002), lower positive rate of ANCA (<0.001) and GBM (p=0.02), less extra-renal involvement (p<0.05), lower proportions of crescents (56.3(51.8-62.7) vs 66.7 (56.3-81.3),p<0.001) and glomerular sclerosis(p<0.001), less severe tubulointerstitial lesion (p<0.001) and interstitial inflammation (p<0.001), higher degree of immune complex deposition of IgA, IgM, C3, C4 and C1q by Immunofluorescence. Normal eGFR group received lower frequency of intravenous methylprednisolone pulse therapy (71.2% vs 89%, p=0.044) and dialysis treatment (0% vs 53.7%, p<0.001). The 5- and 10-year cumulative renal survival rates from ESRD were 90.7% vs 45.5% and 58.3% vs 43.7%, respectively in normal and low eGFR group.
Conclusion. Crescentic GN may present with normal renal function, which have poor renal outcomes and may benefit from intensive immunosuppressive treatment. This often occurs in patients with abnormal immunological indicators and systemic autoimmune disease. Shorter time from onset to biopsy may help better management and improve long-term outcomes in these cases. Renal biopsy remains the diagnostic gold standard when urinary abnormalities are present in nephritis.
Identifying the Land Use Land Cover (LULC) Classifications and Change Using Google Earth Engine (GEE): A Case Study of Narayanganj District, Bangladesh
Authors: Haque S. M. Nazmul , Uddin A S M Shanawaz
Published: June 2024

Natural landscape has been changing day by day in the cities of developing countries like Bangladesh due to rapid urbanization, industrial development and population growth. The current research focuses on LULC classification and changes of a fastest growing district Narayanganj, Bangladesh over the past twenty years. A soft computing supervised machine learning algorithm have been developed using cloud-based computing platform Google Earth Engine to perform the LULC classification and change detection analysis. Landsat-7 TOA imageries are used with Random Forest classifier to classify the LULC for the five different years (2000, 2005, 2010, 2015 and 2020). LULC change detection analysis between 2000 and 2020 has shown that 88.06% increase in urban area, 70.77% decrease in bare area and 36.72% decrease in water area.
Exploring the Programmability of Autocatalytic Chemical Reaction Networks
Authors: Wong Albert , Kriukov Dmitrii , Huskens Jurriaan
Published: June 2024

Chemical reaction networks (CRNs) could offer chemical complexity1 to contribute to future intelligent material design2 or neuromorphic computing technologies3,4. Recent advances in systems chemistry use the complex Belousov–Zhabotinsky5-7 and Formose reactions8,9, or simpler chemical systems with fewer feedback loops10-12, to demonstrate that (spatio)temporal patterns can be harnessed to emulate properties important for intelligent behavior (i.e., the ability to perceive information and retain it as knowledge to execute complex tasks13). In all examples, autocatalysis appears an essential element for facilitating a nonlinear response. How this chemical analogue of a positive feedback mechanism14,15 can be reconfigured in a programmable manner is, however, unknown. Here, we developed a strategy that uses metal ions (Ca2+, La3+, and Nd3+) to control the rate of a trypsin-catalysed autocatalytic reaction network. A flow setup is employed to sustain the reaction network under out-of-equilibrium conditions and demonstrate that various kinetically controllable responses can be mapped onto polynomial and Boolean functions. Remarkably, these functions cannot only be programmed but their temporal and history-dependent nature bestows them with neuromorphic properties, promising novel strategies in designing intelligent chemical systems. Beyond, the easy-to-use method to control autocatalysis will impact future development focusing on biocatalysis, nanobiotechnology, and the chemical origin of life.
Epithelial Cell Adhesion Molecule (EpCAM)-Targeted CAR-T Cells (IMC001) in Patients with Advanced Gastric Cancer: A Phase I Dose-Escalation Trial
Authors: Luo Tianhang , Fang Weijia , Lu Zhengmao , Zheng Rui , Yin Weiwei , Wang Suqiong , Ai Guojiang , Zhong Yunpeng , Zhang Shuangshuang , Hao Ruidong , Sun Minmin
Published: June 2024

Objective
To evaluate the safety and preliminary efficacy of IMC001, an epithelial cell adhesion molecule (EpCAM)-targeted CAR-T cell therapy, in patients with advanced gastric cancer (GC).
Design
This was a phase I, open-label, single or multiple infusion, dose escalation study utilizing a classic 3+3 design that included adults (aged ≥18 years) with locally advanced or metastatic GC with positive EpCAM histological staining of a biopsy tumor tissue sample who had failed at least two lines of treatment and were ineligible for a standard treatment. Eligible patients received IMC001 at doses of 3×105 (low), 1×106 (middle) or 3×106 (high) CAR-T cells/kg after lymphodepletion. The primary objective was evaluation of the safety and tolerability of IMC001. Secondary objectives included determination of the recommended phase II dose (RP2D) based on dose-limiting toxicity (DLT), preliminary evaluation of efficacy and characterization of pharmacokinetics and pharmacodynamics.
Results
From August 18, 2021 to May 8, 2023, 11 patients with advanced GC received IMC001, the median age was 53 (36-70) years and 63.6% (7/11) were male. Most patients 91.9% (10/11) had failed ≥2 lines of chemotherapy and 27.3% (3/11) had received prior immunotherapy. By the cutoff date (March 31st, 2024), low- and middle-dose IMC001 infusion was associated with a favorable safety profile. The disease control rate was 90% in 10 evaluable patients; 1 patient in the low-dose group (1/3, 33.3%) and 2 in the middle-dose group (2/5, 40%) achieved a partial response (PR). The median PFS was 18.1 weeks (95% CI 7.97, --) and the OS was 55.1 weeks (95% CI 23.78, --) for the middle dose group; 3/5 patients in the middle dose group had survived more than 10 months. One patient in the middle-dose group achieved a confirmed PR by Week 24, culminating in a radical gastrectomy at Week 27 and had survived for more than 22 months by the cutoff date. Tumor immune microenvironment analysis suggested that an inflamed tumor environment may enhance the anti-tumor effects of IMC001. The 1×106 CAR-T cells/kg dose was selected as the recommended dose for future study.
Conclusion
In this phase I dose-escalation trial, IMC001 demonstrated a favorable safety profile and encouraging efficacy in patients with advanced, pre-treated GC. Further investigation is warranted to further evaluate the use of IMC001 for patients with advanced GC.
General structured light generation based on programmable linearly-polarized mode synthesizer
Authors: Li Juhao , Chen Wei , Gao Yuyang , Li Xiaofeng , Ge Dawei , Chen Zhangyuan , he yongqi , Ren Fang
Published: June 2024

Fiber-based structured light including cylindrical vector beams (CVBs) and orbital angular momentum (OAM) has gained significant interest in various areas of study for the unique properties of spatial intensity, phase, and polarization distributions. Different approaches have been proposed for the generation of these spatially structured beams such as beam reshaping or directly lasing from specific cavities. In this work, we propose the concept of programmable linearly-polarized (LP) -mode Synthesizer for general structured light generation, in which an LP-mode Pool supporting independent and selectable LP-mode output is first established, and then different CVB/OAM modes could be generated in general way through polarization and phase control according to their conversion relation with LP modes. We demonstrate a proof-of-concept LP-mode Synthesizer based on a fiber ring laser characterized by partial 5-LP mode weakly-coupled few-mode fiber (FMF) cavity and arbitrary LP-mode switch array. Various CVB/OAM beams including TE01, TM01, OAM+1, OAM-1, OAM+2, and OAM-2 modes are successfully generated. This approach provides new insights into mode manipulation methods and could enhance the performance of various structured light applications such as optical and quantum communications, optical fiber sensing, microscopy, and optical trapping.
Herbal Extracts in Orofacial Pain: Systematic Review, Direct and Indirect Meta-analysis
Authors: Barrera Sara Delgadillo , Cepeda Lilia Jadith Bernal , Báez David Augusto Díaz , Kwon Jennifer , Siddiq Abdelmonem , Parra Jaime Eduardo Castellanos , Chaurasia Akhilanand , Marya Anand
Published: June 2024

There is limited knowledge regarding the efficacy of the use of herbal extracts in orofacial pain. A systematic review and a meta-analysis of randomized controlled trials, to assess the analgesic effect of herbal extracts on pain intensity in various painful orofacial conditions was conducted. Sixty-two studies were included. The intervention treatment consisted in the use of herbal extracts compared with placebo and/or standard treatment. The primary outcome was pain intensity assessed before and after the intervention, using any pain scale from 0 to 10. Pain scores were compared with baseline scores in each treatment. When compared with standard therapy, the pooled results of the patients who received herbal extracts reported lower pain intensity; in periodontal pain (mean difference [MD] = -0.92, 95% confidence interval [-6.69, 4.85]), oral surgery pain (MD = 18.80 [8.80, 28.79]), oral neuropathic pain (MD = 20.34 [6.16, 34.52]), endodontic pain (MD = -8.04 [-11.72, -4.37]), oral mucosal pain (MD = 8.74 [2.76, 14.73]), and temporomandibular pain (MD = 30.94 [6.04, 55.83]). The findings indicate a pain-attenuating effect of herbal extracts such as Cannabis, Turmeric, Capsaicin, Licorice, Ginger, Chamomile, Clove, Hypericum perforatum, Arnica montana, Aloe vera and Calendula use in oral surgery pain, oral neuropathic pain, oral mucosal pain, and temporomandibular pain. The findings of this study indicate that herbal extracts may provide a valuable alternative to traditional pain medication. Additionally, it may also be a promising source for developing new active ingredients for pharmaceuticals.
Cyclophosphamide: Potential Hepatorenal Toxicity and the Possible Therapeutic Role of Mesenchymal Stem Cell-Derived Exosomes in Wistar Rats
Authors: Abdallah Ahmed Nour Eldine , Effat Heba , Mousbah Ahmed M. , Ahmed Hanaa H. , Abohashem Rehab S.
Published: June 2024

Background:Cyclophosphamide (CTX) is an alkylating agent widely described in management of several non-neoplastic and neoplastic disorders. The most observed adverse consequence of CTX is organ damage. Exosomes derived from mesenchymal stem cells (MSCs-Exos) have been shown to exhibit therapeutic effects in various tissue-injury models. Aim: The aim of this work was to examine impact of AD-MSCs-Exos in a rat model of hepatorenal toxicity.Methods:32 rats were grouped into 4 groups (n=8): Control group: rats received intraperitoneally (i.p.) PBS (phosphate buffered saline), CTX group: rats injected i.p. with a single dose of CTX (50 mg/kg) followed by rotating doses of 8 mg/kg of CTX daily for 2 weeks, CTX+AD-MSCs group: rats infused with (1×106AD-MSCs cells/rat) dissolved in PBS intravenously (i.v.) day after day for one week starting from second day of CTX last dose, and CTX+AD-MSCs-Exos group: rats injected with 100 μg of Exos derived from AD-MSCs in 1 ml PBS by i.v. injection for one week starting from second day of CTX last dose. 5 weeks following initial CTX dose, blood, liver, and kidneys were extracted. Serum ALT, AST, creatinine and urea levels; hepatic malate dehydrogenase (MDH) and glutamate dehydrogenase (GLDH); renal kidney injury molecule-1 (KIM-1) and clusterin were measured. The inflammatory molecule (TNF-α) and malonialdehyde (MDA); lipid peroxidation one were estimated in hepatic and renal tissues. Furthermore, NF-κB/TLR-4, Nrf-2/HO-1 and Bax/Bcl-2 signaling pathways were analyzed by qRT-PCR. Immunohistochemical staining for cyclooxygenase-2 "COX-2" and inducible nitric oxide synthase "iNOS" were also performed in hepatic and renal tissues. Finally, histopathological investigation of both liver and kidney tissue was carried out.Results:treatment with AD-MSCs-Exos improved liver and kidney functions, diminished oxidative stress (MDA) and enhanced antioxidative Nrf-2/HO-1 pathway; inhibited inflammatory response (TNF-α) and NF-κB/TLR-4 pathway; and downregulated apoptotic Bax/Bcl-2 signaling pathway compared to CTX and CTX+AD-MSCs treated groups. Also, immunological and histopathological investigation verified curative effect of AD-MSCs-Exos against CTX-induced hepatorenal toxicity.Conclusion:these findings uncovered therapeutic impact of AD-MSCs-Exos against hepatorenal insult from holistic perspective. The mechanisms behind this action included restoration of oxidant/antioxidant equilibrium, inhibition of inflammatory reaction and suppression of apoptotic machinery.
Inertia or unanticipated bottlenecks? Exploring the implementation determinants of the national alcohol policy five years post-enactment in Zambia
Authors: Silumbwe Adam , Sebastian Miguel San , Zulu Joseph Mumba , Michelo Charles , Johansson Klara
Published: June 2024

Background
Alcohol use accounts for a huge proportion of the global burden of disease, and many countries grapple with its severe negative social and health consequences. In 2018, Zambia adopted a national alcohol policy with the aim to reduce the prevalence and impact of harmful alcohol use. However, five years post-adoption, the policy implementation has been slow. This study sought to explore the implementation determinants of the national alcohol policy five years post-enactment.
Methods
We employed an exploratory qualitative case study using data collected from 25 in-depth interviews targeting government ministries, civil society, and agencies responsible for enforcing the alcohol policy. We applied both inductive and deductive manifest thematic analysis using Bullock’s analytical framework for understanding the determinants of implementing evidence-based policies.
Results
The alcohol policy provided a comprehensive framework for action, yet its policy directives remained unclear. A restructured policy coordination committee rejuvenated the momentum to implement the policy. However, weak collaboration between the council and state police hampered the enforcement of alcohol laws. Implementing agencies faced obstacles such as lack of financial and human resources, absence of rehabilitation services, and misapplication of alcohol selling licences. Further, community indifference, inaction, and resistance to alcohol control laws affected the policy implementation. The socio-political environment contributed to implementation challenges through framing alcohol as an economic development issue and culturally tolerating harmful alcohol use. Additionally, changes in government affected policy ownership while unregulated illicit alcohol production and the sale of traditional and imported spirits further hampered the implementation of the policy.
Conclusion
Overcoming implementation hurdles for contentious health policies demands comprehensive strategies such as engaging communities, challenging cultural norms, strategically assigning funding, and fostering collaboration among implementing agencies. In the case of Zambia's national alcohol policy, this may take the form of leveraging enablers such as stakeholder recognition of the policy framework and the restructured committee for the coordination of policy implementation, now under local government oversight. Key actions should include empowering local government to enforce measures to reduce unregulated alcohol availability and ensure adequate resource allocation for alcohol control activities among implementation agents, including those providing treatment and rehabilitation services.
Cell growth and mitochondrial anomalies in induced pluripotent stem cells with Presenilin 1 mutation
Authors: Hamam Rimi , Hanna Roy , Barabino Andrea , Serhani Dounya , Tavares Erika , Élise Héon , Bernier Gilbert
Published: June 2024

Presenilin 1 (PSEN1) is the most frequently mutated gene in early-onset sporadic and familial Alzheimer’s disease (FAD). The PSEN1 complex displays gamma-secretase activity and promotes cleavage of the C99-terminal fragment of the Amyloid Precursor Protein (APP) into the Aβ42 peptide. PSEN1 is also involved in vesicle transport across ER and mitochondria in so called mitochondria associated membranes. We generated induced pluripotent stem cells (iPSCs) from 4 controls and 5 FAD cases carrying the PSEN1 A246E and L286V mutations. Unexpectedly, global gene expression profile analysis of FAD iPSCs revealed profound perturbation of mitochondrial, Golgi apparatus and ER pathways. FAD iPSCs grown slower and showed elevated cell death together with abnormally high Aβ42 secretion. Mitochondrial reactive oxygen species (ROS) were elevated in FAD iPSCs and treatment with a ROS scavenger significantly improved cell death and proliferation. However, it could not improve the severe ATP deficit. Inhibition of gamma-secretase activity further exacerbated the overall FAD iPSC phenotype. Consistently, PSEN1, APP and Nicastrin were highly expressed in iPSCs and where PSEN1 localized to the cell’s membrane. Cortical neurons produced from the differentiation of FAD iPSCs showed Alzheimer’s pathology and TGFβ pathway hyper-activation. PSEN1-mutant iPSCs may serve as a new model to perform genome-wide genetic screens and to study FAD pathophysiology and PSEN1 cellular function.
A Systematic Literature Review on Transparencyand Interpretability of AI models in Healthcare:Taxonomies, Tools, Techniques, Datasets, OpenResearch Challenges, and Future Trends
Authors: Shafik Wasswa , Hidayatullah Ahmad Fathan , Kalinaki Kassim , Gul Haji , Zakari Rufai Yusuf , Tufail Ali
Published: June 2024

The increased utilization of disruptive health and biomedical informatics technologies, such as artificial intelligence (AI), has accelerated medical operations from patient-centered medical experience data management to simplified medical procedures in this generative era. As these technologies integrate into traditional approaches, they raise critical medical concerns, entailing transparency and interpretability of these AI models. This study conducts a systematic literature review (SLR) and presents an exhaustive review of the studies using data collection procedures and publicly available academic databases. 1837 articles published between 2014 and 2024 were obtained from eight popular academic databases: PubMed, ACM Library, Springer, Scopus, IEEE Xplore, ScienceDirect, Google Scholar, and Web of Science. A comprehensive screening process was used, and 148 articles were considered based on the relevance of the AI method to healthcare and biomedical. The studied studies demonstrate that the majority of medical people still find it complex to effectively explain the reasoning behind the decisions AI models make during biomedical experiments, leading to limited trust, biased decision-making, and unknown patient data safety. Model-agnostic strategies and explainable AI (XAI) frameworks are inspected, together with crucial datasets for training and assessment. The main challenges are AI model intricacy and regulatory compliance, while future trends highlight fairness and predisposition mitigation. Limited studies are focusing on improving AI openness, trust, and interpretability. Towards the end, it reveals that there is still a big research gap in descriptive explainable AI models in healthcare when integrating AI into clinical practice while maintaining ethical standards and patient-centric care.
Evaluation of the compressive strength, solubility, radiopacity, and flow of bromelain-modified biodentine for direct pulp capping
Authors: Agrawal Paridhi , Chandak Manoj , Patel Aditya , Bhopatkar Jay
Published: June 2024

Background
This study aims to evaluate the compressive strength, solubility, radiopacity, and flow of bromelain (BR)-modified biodentine (BD) for direct pulp capping (DPC). This is suggested to find out the impact of BR on the physical properties of BD.
Methods
A total of 80 samples were prepared according to ISO and ADA specifications and evaluated for compressive strength, solubility, radiopacity, and flow. Independent sample t-tests were used to assess the data statistically and then compare the means with p-value ≤ 0.05.
Results
The results revealed that BR-modified BD showed a significantly higher mean value of flow and similar mean values of compressive strength, solubility, and radiopacity as that of BD (P ≤ 0.05).
Conclusion
BR-modified BD maintains BD's physical properties, with improved flow, making it a promising DPC agent warranting further study.
Study of microwave magnetic field saturation properties of an inhomogeneous CW-EPR line in the vicinity of Rabi resonance: Possible application for B 1 estimation
Authors: Rakvin Boris , Jurec Jurica
Published: June 2024

The spectrum of continuous wave electron paramagnetic resonance (CW-EPR) was analyzed with respect to the shape of the line under microwave (MW) power saturation (\({P}_{MW}\sim{B}_{1}^{1/2};{B}_{1 }\)is intensity of MW magnetic field). The used \({B}_{1 }\) increases until the Rabi frequency \(({\omega }_{1}=\gamma {B}_{1}\), \(\gamma\)is the electron gyromagnetic ratio) approaches the radiofrequency \(\left({\omega }_{rf}\right)\) used as the magnetic modulation frequency. The possible effect of Rabi resonance \(\left({\omega }_{1}={\omega }_{rf}\right)\), on spin packets system can be detected under the condition of “weak modulation near the Rabi resonance” (\({\omega }_{2}\ll {\omega }_{1}\approx {\omega }_{rf})\) where \({\omega }_{2}\) is modulation amplitude of radiofrequency field expressed in frequency units. Inhomogeneously broadened, CW-EPR, lines of the P1 (Ns0) nitrogen centers (30ppm>[Ns0] <200ppm) in diamond crystal and E’ defect in irradiated vitreous SiO2 with long spin relaxation times (\({T}_{1}\) and \({T}_{2}\)ranged in the interval from around 2ms to 1 µs at room temperatures) were selected for saturation study. Spectra were recorded using magnetic field modulation \(({\omega }_{rf}/2\pi =100\) kHz) with modulation amplitude\(({\omega }_{2}/2\pi =27 \text{k}\text{H}\text{z})\) as the first harmonic for two phase-sensitive detections, detection in-phase with respect to the modulation frequency and detection 90o out-of-phase with respect of the modulation frequency. The resulting changed in inhomogeneous spectral lines of P1 and E’ centers detected near Rabi resonance in the saturation process shows that both samples can be used as a standard for estimation \({B}_{1}\) value.