bluuebunny/crossref_metadata_2025 huggingface dataset:
Network pharmacology, computational biology integrated surface plasmon resonance technology reveals the mechanism of ellagic acid against rotavirus
Authors: Zheng Jiangang , Haseeb Abdul , Wang Ziyang , Wang Hejie
Published: March 2024

The target and mechanism of ellagic acid (EA) against rotavirus (RV) were investigated by network pharmacology, computational biology, and surface plasmon resonance verification. The target of EA was obtained from 11 databases such as HIT and TCMSP, and RV-related targets were obtained from the Gene Cards database. The relevant targets were imported into the Venny platform to draw a Venn diagram, and their intersections were visualized. The protein–protein interaction networks (PPI) were constructed using STRING, DAVID database, and Cytoscape software, and key targets were screened. The target was enriched by Gene Ontology (GO) and KEGG pathway, and the ‘EA anti-RV target-pathway network’ was constructed. Schrodinger Maestro 13.5 software was used for molecular docking to determine the binding free energy and binding mode of ellagic acid and target protein. The Desmond program was used for molecular dynamics simulation. Saturation mutagenesis analysis was performed using Schrodinger's Maestro 13.5 software. Finally, the affinity between ellagic acid and TLR4 protein was investigated by surface plasmon resonance (SPR) experiments. The results of network pharmacological analysis showed that there were 35 intersection proteins, among which Interleukin-1β (IL-1β), Albumin (ALB), Nuclear factor kappa-B1 (NF-κB1), Toll-Like Receptor 4 (TLR4), Tumor necrosis factor alpha (TNF-α), Tumor protein p53 (TP53), Recombinant SMAD family member 3 (SAMD3), Epidermal growth factor (EGF) and Interleukin-4 (IL-4) were potential core targets of EA anti-RV. The GO analysis consists of biological processes (BP), cellular components (CC), and molecular functions (MF). The KEGG pathways with the highest gene count were mainly related to enteritis, cancer, IL-17 signaling pathway, and MAPK signaling pathway. Based on the crystal structure of key targets, the complex structure models of TP53-EA, TLR4-EA, TNF-EA, IL-1β-EA, ALB-EA, NF-κB1-EA, SAMD3-EA, EGF-EA, and IL-4-EA were constructed by molecular docking (XP mode of flexible docking). The MMGBS analysis and molecular dynamics simulation were also studied. The Δaffinity of TP53 was highest in 220 (CYS → TRP), 220 (CYS → TYR), and 220 (CYS → PHE), respectively. The Δaffinity of TLR4 was highest in 136 (THR → TYR), 136 (THR → PHE), and 136 (THR → TRP). The Δaffinity of TNF-α was highest in 150 (VAL → TRP), 18 (ALA → GLU), and 144 (PHE → GLY). SPR results showed that ellagic acid could bind TLR4 protein specifically. TP53, TLR4, and TNF-α are potential targets for EA to exert anti-RV effects, which may ultimately provide theoretical basis and clues for EA to be used as anti-RV drugs by regulating TLR4/NF-κB related pathways.
Follicular metabolic alterations are associated with obesity in mares and can be mitigated by dietary supplementation
Authors: Catandi Giovana D. , Fresa Kyle J. , Cheng Ming-Hao , Whitcomb Luke A. , Broeckling Corey D. , Chen Thomas W. , Chicco Adam J. , Carnevale Elaine M.
Published: March 2024

Obesity is a growing concern in human and equine populations, predisposing to metabolic pathologies and reproductive disturbances. Cellular lipid accumulation and mitochondrial dysfunction play an important role in the pathologic consequences of obesity, which may be mitigated by dietary interventions targeting these processes. We hypothesized that obesity in the mare promotes follicular lipid accumulation and altered mitochondrial function of oocytes and granulosa cells, potentially contributing to impaired fertility in this population. We also predicted that these effects could be mitigated by dietary supplementation with a combination of targeted nutrients to improve follicular cell metabolism. Twenty mares were grouped as: Normal Weight [NW, n = 6, body condition score (BCS) 5.7 ± 0.3], Obese (OB, n = 7, BCS 7.7 ± 0.2), and Obese Diet Supplemented (OBD, n = 7, BCS 7.7 ± 0.2), and fed specific feed regimens for ≥ 6 weeks before sampling. Granulosa cells, follicular fluid, and cumulus-oocyte complexes were collected from follicles ≥ 35 mm during estrus and after induction of maturation. Obesity promoted several mitochondrial metabolic disturbances in granulosa cells, reduced L-carnitine availability in the follicle, promoted lipid accumulation in cumulus cells and oocytes, and increased basal oocyte metabolism. Diet supplementation of a complex nutrient mixture mitigated most of the metabolic changes in the follicles of obese mares, resulting in parameters similar to NW mares. In conclusion, obesity disturbs the equine ovarian follicle by promoting lipid accumulation and altering mitochondrial function. These effects may be partially mitigated with targeted nutritional intervention, thereby potentially improving fertility outcomes in the obese female.
Gorilla optimization algorithm combining sine cosine and cauchy variations and its engineering applications
Authors: Wang Shuxin , Cao Li , Chen Yaodan , Chen Changzu , Yue Yinggao , Zhu Wenwei
Published: March 2024

To address the issues of lacking ability, loss of population diversity, and tendency to fall into the local extreme value in the later stage of optimization searching, resulting in slow convergence and lack of exploration ability of the artificial gorilla troops optimizer algorithm (AGTO), this paper proposes a gorilla search algorithm that integrates the positive cosine and Cauchy's variance (SCAGTO). Firstly, the population is initialized using the refractive reverse learning mechanism to increase species diversity. A positive cosine strategy and nonlinearly decreasing search and weight factors are introduced into the finder position update to coordinate the global and local optimization ability of the algorithm. The follower position is updated by introducing Cauchy variation to perturb the optimal solution, thereby improving the algorithm's ability to obtain the global optimal solution. The SCAGTO algorithm is evaluated using 30 classical test functions of Test Functions 2018 in terms of convergence speed, convergence accuracy, average absolute error, and other indexes, and two engineering design optimization problems, namely, the pressure vessel optimization design problem and the welded beam design problem, are introduced for verification. The experimental results demonstrate that the improved gorilla search algorithm significantly enhances convergence speed and optimization accuracy, and exhibits good robustness. The SCAGTO algorithm demonstrates certain solution advantages in optimizing the pressure vessel design problem and welded beam design problem, verifying the superior optimization ability and engineering practicality of the SCAGTO algorithm.
Recent advances in CdS heterojunctions: morphology, synthesis, performances and prospects
Authors: Wang Wenchao , Xue Jing , Liu Jixian
Published: March 2024

The morphology of CdS heterojunctions, which can be rationally designed and fabricated via controllable synthesis approaches, influences their photocatalytic performance.
Cobalt-based hybrid nanoparticles loaded with curcumin for ligand-enhanced synergistic nanocatalytic therapy/chemotherapy combined with calcium overload
Authors: Li Mengyang , Lu Zijie , Fang Chao , Zheng Bingzhu , Fu Yike , Li Xiang
Published: March 2024

CaCO3-mineralized cobalt-based nanocatalysts were synthesized and loaded with curcumin for synergistic nanocatalytic therapy/chemotherapy combined with calcium overload. Curcumin acts as a ligand and an electron donor to enhance the efficacy of nanocatalytic therapy.
Enhancing reverse intersystem crossing and horizontal dipole orientation for near-infrared thermally activated delayed fluorescence molecules by donor engineering strategy
Authors: Fan Jianzhong , Liu Huanling , Song Yuzhi , Lin Lili , Wang Chuan-Kui , Xu Yuanyuan , Zhao Xin
Published: March 2024

Improving the internal quantum efficiency and optimizing the horizontal dipole orientation in near-infrared thermally activated delayed fluorescence (TADF) molecules are highly desired.
Direct X-ray detectors made of zero-dimensional hybrid metal halide perovskite single crystals
Authors: Zheng Guangya , Wu Haodi , Dong Zhiwu , Jin Tong , Pang Jincong , Liu Yujue , Zheng Zhiping , Niu Guangda , Xu Ling , Tang Jiang
Published: March 2024

A novel zero-dimensional cadmium hybrid metal halide (C19H18P)2CdCl4 single crystal was synthesized by inserting (C19H18P)+ into a [CdCl4]2− tetrahedron lattice through a slow volatilization method, which was proved to be a promising X-ray detector.
Transfer force perception skills to robot‐assisted laminectomy via imitation learning from human demonstrations
Authors: Li Meng , Qi Xiaozhi , Han Xiaoguang , Hu Ying , Li Bing , Zhao Yu , Zhang Jianwei
Published: March 2024

A comparative study of two force perception skill learning approaches for robot‐assisted spinal surgery, the impedance model method and the imitation learning (IL) method, is presented. The impedance model method develops separate models for the surgeon and patient, incorporating spring‐damper and bone‐grinding models. Expert surgeons' feature parameters are collected and mapped using support vector regression and image navigation techniques. The imitation learning approach utilises long short‐term memory networks (LSTM) and addresses accurate data labelling challenges with custom models. Experimental results demonstrate skill recognition rates of 63.61%–74.62% for the impedance model approach, relying on manual feature extraction. Conversely, the imitation learning approach achieves a force perception recognition rate of 91.06%, outperforming the impedance model on curved bone surfaces. The findings demonstrate the potential of imitation learning to enhance skill acquisition in robot‐assisted spinal surgery by eliminating the laborious process of manual feature extraction.
Economic scheduling method for voltage‐dependent loads in a power system based on a multitime scale framework
Authors: Niu Tao , Tian Linxuan , Fang Sidun , Chen Guanhong
Published: March 2024

There are many voltage‐dependent loads (VDLs) in power systems. When the unit reserve supply is low, the transmission network adjusts the voltage of grid‐connected nodes to provide additional resources. Many reactive power devices with different regulatory performance levels and timescales must be coordinated to employ flexible VDLs to the maximum extent, and consequently, a transient stability‐constrained optimal power flow (TSCOPF) problem with mixed integers and multiperiod coupling must be solved. A multitimescale scheduling ‘day‐ahead‐intraday‐real‐time’ framework is designed for the optimal economic scheduling of VDLs. In the day‐ahead stage, the optimal scheduling period of the discrete reactive power control devices is determined. In the intraday stage, a rolling optimization model based on model predictive control is established, and the specific action times of the discrete reactive power devices are determined. In the real‐time stage, the optimal regulation strategy of the continuous reactive power control device is optimized by rolling. Then, to consider the speed and accuracy of the solution at the same time, a continuous sensitivity correction method is adopted to simplify and solve the original model. Finally, with a modified IEEE‐39 system and a modified IEEE‐118 system as examples, it is verified that the multitimescale scheduling framework maximizes the exploitation of the flexible resources of VDLs to ensure voltage security and stability and improve the economy of system operation under different scenarios.
Effect of Microneedle on Hair Regrowth in Patients with Androgenetic Alopecia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Xu Chunyan , Duan Xingwu , Yin Qiang , Liu Keshuai
Published: March 2024

Objective Our objective was to assess the effectiveness and safety of microneedle by comparing microneedle plus 5% topical minoxidil treatment and microneedle alone to 5% topical minoxidil.

Methods We searched databases such as Embase, PubMed, Cochrane library, VIP Database for Chinese Technical Periodicals, Wanfang, and China National Knowledge Infrastructure in relation to literature. The control group received 5% topical minoxidil solution, whereas the treatment group received either microneedle coupled with minoxidil or microneedle alone. The increase in hair count and hair diameter was the main evaluation criterion for assessing hair regrowth. Data were pooled with Stata 15 software.

Results Eight studies with 472 participants were included. Compared with 5% topical minoxidil therapy, microneedle plus minoxidil treatment showed a significant increase in hair count (standard mean difference [SMD] :15.82, 95% confidence interval [CI]: 12.34, 19.31, p < 0.05), but no increase in hair diameter (SMD: −0.21, 95% CI: −2.94, 2.52, p = 0.879 > 0.05). The results of subgroup analysis suggested that microneedle plus minoxidil treatment showed a significant increase in hair count whether the depth of microneedle was less than 1 mm (SMD:1.16, 95% CI: 0.86, 1.42, p < 0.05) or more than 1 mm (SMD:0.52, 95% CI: 0.23, 0.82, p < 0.05). In terms of treatment period subgroup, microneedle combined with minoxidil therapy significantly increased hair count and hair diameter than single 5% topical minoxidil, whether in 12-week period (SMD: 1.08, 95% CI: 0.76, 1.39, p < 0.05) or 21 to 24 weeks period (SMD: 0.64: 95%, CI: 0.35, 0.92, p < 0.05).

Conclusion According to this study, the effect of microneedle treatment alone on androgenetic alopecia (AGA) may be limited. However, microneedle plus 5% topical minoxidil treatment had better hair regrowth in hair count and can be considered as an additional therapy option for AGA. Combined with subgroup analysis results, 12-week period and less than 1 mm depth of microneedle penetration were recommended.
Enhanced External Counterpulsation Outcomes Study: Retrospective Analyses of Data Obtained from Patients at a Single Medical Center in United States
Authors: Akula Ashok , Grafft Heidi R. , Tak Nadia , Haberman Douglas A. , Tak Tahir
Published: March 2024

The aim was to explore the effectiveness of enhanced external counterpulsation (EECP) therapy in patients with severe angina pectoris/ chronic heart failure symptoms, who were not suitable candidates for invasive treatment. This retrospective study employed a comprehensive methodology that includes individualized treatment, continuous monitoring, and thorough pre- and postprogram evaluations to assess the efficacy of EECP therapy. The standard protocol involved 35 one-hour treatments, with flexibility for extensions based on therapeutic progress. When pre- and posttreatment results were analyzed, EECP improved the original functional class compared with pretreatment. The mean difference in the functional class was 1.32 (0.92), p < 0.0001. Six-minute walk (6MW) distance improved from 383.6 m (110.24) to 423.1 m (121.50) with mean difference of 37.1 (44.99), p < 0.0001. Duke Activity Status Index (DASI) score improved from 3.9 (2.75) to 6.0 (4.17) with mean difference of 2.16 (3.8), p < 0.0001. Training metabolic equivalents (METs) improved from 3.0 (0.74) to 4.0 (1.57) with mean difference of 1.04 (1.2), p < 0.0001. Weekly anginal events decreased from 13.1 (13.19) to 3.2 (7.38) with mean difference of –9.78 (11.7), p < 0.0001. EECP resulted in improvement of angina pectoris functional class, the 6MW distance, reduction in the number of hospitalizations in first year posttreatment, a significant decrease in sublingual nitroglycerin use, improvement of systolic and diastolic blood pressure, and improvement of DASI score.
Geospace translation strategies and their cognitive construal
Authors: Sun Jinyi , He Aijun
Published: March 2024

Since the literary geospace is usually tinged with the author’s embodied experiences, it calls on the translator to restore or reconstruct the ST geospace’s geographical reality or imagination in the target language culture. Based on the embodied cognition of the environment, the translator can wash and negotiate the geographical conceptual system of the ST geospace by resorting to the three translation strategies, i.e., retention, reconstruction, and substitution, so as to generate new geospace in the geographical conceptual system of the TL. The article aims to analyze geospace translation strategies from the perspective of conceptual blending theory. The translator’s use of different translation strategies results from different mapping paths among the spaces of the source text, of the translator, and of the target text. It can illustrate the regularities of the translator’s space mediation in translating the geospace. Retention signifies the single-domain mappings from the space of ST. Substitution indicates the single-domain mappings from the space of the translator. Reconstruction denotes the double-domain mappings from both the spaces of ST and the translator. The emergent structure generated in the space of the target text yields the reterritorialization of the geospace in the target language culture, which can stimulate the reader of TT to get a similar geographical experience to that of the author and to empathize with the author’s sense of place to a greater extent.
Floral colour variation across life history and geography in Mimulus ringens (Phrymaceae)
Authors: White Sarah V , Royer Anne M
Published: March 2024

Floral and life history traits play important roles in plant speciation. The genus Mimulus is a model system for studying speciation. It includes examples of species in which floral colour facilitates isolation through pollinator shifts, as well as life history changes that result in temporal or ecogeographic isolation. We investigate the possibility that both floral colour and life history have shifted together in a recently described, genetically distinct group within the species Mimulus ringens. Using a large, range-wide citizen science dataset, we test for geographic trends in flower colour and flowering time. We combine this with greenhouse studies in populations of known life history to test for differences in flower colour with life history. We show that darker-flowered plants are more common at higher latitudes, that annual-like populations have darker flowers, and that flowering time varies with latitude only in the subset of populations that have lighter flowers. This suggests that annual-like populations (with the earlier flowering time typical of this life history) are restricted to the northern part of the species range and may have distinct trends in flowering date.
Development and Validation of Chromatographic Methods for Simultaneous Estimation of Aspirin and Pantoprazole Sodium in Pure and Mixture Form
Authors: Chandarana Chandni , Desai Heli , Chauhan Ayushi , Parmar Vijaykumar , Prajapati Parixit
Published: March 2024

This technique is employed for the simultaneous quantification of aspirin (ASP) and pantoprazole sodium in both pure powder form and formulations. The high performance liquid chromatography (HPLC) method uses a C-18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of 0.05 M disodium hydrogen phosphate and methanol in a 40:60% v/v ratio. The flow rate is maintained at 1.0 mL/min. On a layer of silica gel 60F254 with an aluminum backing, the high performance thin layer chromatography (HPTLC) separation was carried out with ethyl acetate and methanol (8: 1.5 v/v) as the mobile phase. With a mean recovery of 100.54% and 99.55% for ASP and PNT, respectively, quantification was accomplished using the HPLC method with UV detection at 286 nm over the concentration range of 0.1–0.6 g/mL for PNT and 0.4–2.4 g/mL for ASP. With a mean recovery of 99.44% and 99.01% for ASP and PNT, respectively, quantification was achieved using the HPTLC method with UV detection at 298 nm over the concentration range of 400–2400 ng/spot for ASP and 100–600 ng/spot for PNT, respectively. The methods can be used for the simultaneous determination of ASP and PNT in pure powder form and formulations as they are simple, accurate and sensitive.
Quality Evaluation of Shexiang Tongxin Dropping Pill Based on HPLC Fingerprints Combined with HPLC-Q-TOF-MS/MS Method
Authors: Lin Ming , Xu Chun-ling , Pan Hong-ye , Song Yong-biao , Ma Yi-wen , Liu Xing-yu , Yao Jian-biao , Wang Ru-wei
Published: March 2024

Shexiang Tongxin Dropping Pill (STP) is a composite formula of traditional Chinese medicine that is widely used for the treatment of cardiovascular diseases. It consists of seven medicinal extracts thereof or materials, including Bufonis venenum, synthetic Moschus, Panax ginseng, Bovis calculus artifactus, Bear bile powder, Salvia miltiorrhiza Bge and synthetic borneol. However, it is considerably difficult to evaluate the quality of STP due to its complex chemical compositions. This paper was designed to explore a comprehensive and systematic method combining fingerprints and chemical identification for quality assessment of STP samples. Twenty batches of STP samples were analyzed by high-performance liquid chromatography (HPLC) and high-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry. Ten common peaks were detected by HPLC fingerprint similarity evaluation system. Meanwhile, 100 compounds belonging to 4 structural characteristics, including 23 bufadienolides, 36 organic acids, 34 saponins and 7 other types, were systematically identified as the basic components in STP. This study could be used for clarifying the multiple bioactive substances and developing a comprehensive quality evaluation method of STP.
Atypia Involving Fibroadenomas: Outcomes and Upgrade Rates
Authors: Aripoli Allison , Winblad Onalisa , Balanoff Christa , Peterson Jessica , Smith Camron , Huppe Ashley , Hill Molly , Wermuth Daniela , Gloyeske Nika
Published: March 2024

Objective

Fibroadenomas (FAs) involved by atypia are rare. Consensus guidelines for management of FAs involved by atypia when diagnosed on image-guided biopsy do not exist because of limited data reporting surgical upgrade rates to ductal carcinoma in situ (DCIS) or invasive malignancy. Therefore, these lesions commonly undergo surgical excision.

Methods

This single-institution retrospective study identified cases of FAs involved by atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and/or lobular carcinoma in situ (LCIS) diagnosed on image-guided biopsy between January 2014 and April 2023 to determine upgrade rates. Cases with incidental atypia adjacent to but not involving FAs were excluded.

Results

Among 1736 FAs diagnosed on image-guided biopsy, 32 cases (1.8%) were FAs involved by atypia including 43.8% (14/32) ALH, 28.1% (9/32) ADH, 18.8% (6/32) LCIS, 6.3% (2/32) LCIS + ALH, and 3.1% (1/32) unspecified atypia. The most common imaging finding was a mass. Most cases, 81.3% (26/32), underwent subsequent surgical excisional biopsy. A single case of ADH involving and adjacent to an FA was upgraded to FA involved by low-grade DCIS on excision for an overall surgical upgrade rate of 3.8%. There were no cases upgraded to invasive malignancy. For those omitting surgical excision, there was no subsequent malignancy diagnosis at the FA biopsy site over a mean follow-up of 73 months.

Conclusion

Cases of radiologic-pathologic concordant FAs involved by atypia have a low upgrade rate of 3.8% and should undergo multidisciplinary review. Larger multi-institutional analysis is needed to determine whether guidelines for excision of atypia should apply to atypia involving FAs.
Impacts of winter warming events on spruce budworm: the importance of timing
Authors: Moise Eric R D , Warren Jamie , Bowden Joseph J
Published: March 2024

Winter climate change constitutes not only a shift in chronic conditions (i.e., shorter length and warmer average temperatures) but will also influence the dynamics of extreme warming events. The latter may be particularly important for the performance and survival of insects, given their susceptibility to temperature variation. However, metabolic sensitivity changes over the course of winter diapause, and thus, insect responses to warming may vary depending on when the event occurs. To determine the influence of warm-up timing, we exposed the spruce budworm, Choristoneura fumiferana ((Clem.), Lepidoptera: Tortricidae), to acute warming events in early-, mid-, and late-dormancy and measured impacts on survival, performance, and biochemistry. While we did not observe any impacts of warm-up timing on performance, survival to the adult stage was significantly reduced in response to earlier warming. Additionally, glycogen concentration was significantly higher in response to early and late warming exposure. Collectively, these results suggest that the timing of extreme winter warming events matters, with consequences for both lethal and sublethal responses.
Effects of protein levels on production performance, nutritional values, and phase feeding of two-spotted cricket
Authors: Kaewtapee Chanwit , Triwai Punsak , Inson Chama , Masmeatathip Roungthip , Sriwongras Piyapong
Published: March 2024

Two experiments were conducted to determine the effects of different protein levels on the growth performance, feed efficiency and nutritional values, and phase feeding of the 2-spotted cricket (Gryllus bimaculatus de Geer). In experiment 1, 4 crude protein (CP) diets were formulated to contain 18%, 20%, 22%, or 24% CP, respectively. A sample of 7-day-old 3,600 crickets was equally divided into 24 plastic boxes (150 crickets each) in a completely randomized design with 4 diets and 6 replications. In experiment 2, 2-phase feedings were used. For starting period (days 7–18), crickets in all treatments were fed a diet containing 22% CP. During the growing period (days 19–35), 3 groups of crickets were fed diets containing 18%, 20%, and 22% CP. In the overall period of experiment 1, the crickets fed with 22% CP diet had greater body weight compared to those fed with 18% CP diet. In addition, the crickets fed with 22% CP diet had the lowest feed conversion ratio (FCR). The broken-line model indicated the growth pattern changed on day 18. In experiment 2, the crickets fed with 20% CP diet from days 19 to 35 had greater growth performance and lower FCR than those fed with 18% CP, but not different from those fed with 22% CP. In conclusion, 22% CP can increase growth performance by improving the feed efficiency of crickets. The implementation of 2-phase feedings using 20% CP, during the growing period, could be considered as a cost-effective strategy for sustainable cricket production.
Redating Barnabas
Authors: Finnis John
Published: March 2024

The undisturbed consensus that three verses in Barnabas (Bn) 16 refer to the Temple’s destruction by Titus, and to a rumoured rebuilding sometime in the subsequent 65 years, neglects to ask whether those verses would make good sense to readers in the generation before Titus. They would, and as references to the destruction by Nebuchadnezzar, and reconstruction by Zerubbabel, vassal of Cyrus, would cohere much better with the preceding 14 chapters. And since the intertextual ‘echoes’ between Bn and Pauline letters (and 1 Peter and Hebrews) are all more plausible when reversed, and the 11th ‘king’ in Bn 4 may be Agrippa I rather than Vespasian, Nerva, or Hadrian, we can look to a date c.40. Then Bn’s linguistic and thematic links with Acts’ accounts of Stephen’s Speech and of Barnabas in Syrian Antioch are best explained if Bn was written by Barnabas to his Antioch congregation, when fetching Paul to Antioch. The classic but long-doubted objections to Barnaban authorship weigh even less if Bn was thus a generation earlier than they assumed. Finally, the sequence of the earliest witnesses to the Christian Two Ways is clarified.
A Case of Multidrug-Resistant Tuberculosis in an Active Duty Military Health Care Worker
Authors: Saunders Amanda E , Shanahan Kevin M , Downs John W
Published: March 2024

Cases of active tuberculosis (TB) in the U.S. Military have fallen over the last century in large part due to improved screening and treatment options. The subset of multidrug-resistant TB (MDR-TB) is almost nonexistent within the U.S. Military. We present a case of MDR-TB in an active duty U.S. Military health care worker and discuss several considerations for treatment that may present challenges for U.S. Military medical practitioners. A 30-year-old active duty Soldier was referred to Army public health services after a bronchoscopy sample was positive for Mycobacterium tuberculosis complex. Sputum smears were negative for acid-fast bacilli, suggesting lower risk for community spread. One month after initiation of the standard 4-drug regimen for active TB, genetic susceptibility testing found the patient’s M. tuberculosis isolate to be resistant to rifampin, isoniazid, and pyrazinamide. Contact investigation efforts among co-workers and family members fortunately found no new interferon-gamma release assay conversions. Coordination of public health assets to ensure a successful treatment regimen occurred across varied local, state, and federal agencies. Atypical medications required coordination with the FDA for procurement. An extensive surveillance plan for medication adverse effects was required. Finally, questions of public health authority versus patient autonomy arose requiring multidisciplinary input and ethical discussions.
Lessons Learned: Large-Scale Perfused Cadaver Training in Three Different Curricular Environments
Authors: Koo Alex Y , Rodgers David K , Hohman Marc H , Muise Jason R , Couperus Kyle S , Phelps Jillian F
Published: March 2024

Background

Perfused cadavers are viable training models for operating room surgical skills, increasing fidelity of vascular anatomy, dissection, and tissue handling. In addition, perfused cadavers may have benefits in military medical training environments with a focus on hemorrhage control and vascular access.

Objectives

We created a large-scale training exercise with perfused cadavers in three different environments and aim to share the curricular design and feedback from the exercise.

Methods

We conducted a 4-day simulation training exercise with 13 perfused cadavers in 3 different environments: hospital environment, the austere echelons of care environment, and a controlled-settings tent for hemorrhage control and needle decompression training. Through an anonymous online survey and an after-action review (AAR), we elicited feedback on advantages, disadvantages, costs, and comparison to models of porcine and fresh cadavers for procedures and existing courses.

Results

A total of 324 participants were trained with 13 perfused cadavers for over 4 days from a variety of specialties and on different procedures and surgical skills. Based on 130 respondents to the survey and the AAR, perfused cadavers were rated to have realistic arterial bleeding and bleeding control training. In addition, perfused cadavers provided increased realism and fidelity for surgical skills. There were disadvantages of logistical requirements, cleanup, costs, and mobility.

Conclusion

Perfused cadavers can be implemented effectively for hemorrhage control training, surgical and procedure skills, and even exercises in austere environments, but require significant logistical and planning considerations. The training value is maximized with a progressive curriculum from hemorrhage control iterations to more invasive surgical procedures, such as thoracotomy and exploratory laparotomy.
Addressing Differences in Knowledge and Experience in Trauma Care Capabilities Among an International Team of Military Medical Care Providers in a Deployed Setting
Authors: Holvelinsky Sarah , Travers Taylor , Stierwalt Joshua B , Schunk Paul , Murray Brian Patrick
Published: March 2024

Military medical personnel are crucial in providing life-saving care at the point of injury (POI) in challenging environments such as combat zones and disaster areas. This article examines the specialized training US Military medical personnel undergo before deployment and the increasing trend of deploying as part of multinational forces in operations like those in Afghanistan with NATO and non-NATO countries. Integrating medical teams from diverse backgrounds poses significant challenges in maintaining a cohesive and efficient team due to varying trauma management training standards and medical practices among the allied forces. Tactical Combat Casualty Care (TCCC) training and the development of clinical practice guidelines (CPG) by the US Joint Trauma Service have been key strategies by the US Military to standardize care. However, the variation in trauma management training among NATO allies and the differences in medical subspecialties and approaches can lead to inefficiencies and reduced effectiveness in a multinational trauma center setting. For instance, the approach to trauma care can significantly differ between the US and European countries, impacting the interoperability and teamwork in multinational medical teams. To address these challenges, the article highlights the importance of standardized medical training programs that include cultural awareness to enhance the effectiveness of multidisciplinary, multinational medical teams. It also underscores the necessity for standardized international trauma training in the face of increasing global conflicts and the potential for large-scale combat operations. The article discusses the “Trauma Tuesday” program implemented in Kabul, Afghanistan, as an example of how intensive training and simulation exercises can improve team dynamics, knowledge, and skills in trauma management among a diverse team from various nations. The need for ongoing education and developing a standard for managing trauma patients in international teams is emphasized to ensure effective communication and coordination. The article suggests that multinational trauma training can significantly improve team cohesion and critical life-saving skills, essential for future battlefields where access to definitive care may be delayed. Further research is recommended to explore the best methods for achieving effective multinational medical team integration and training standardization.
The diversity of splicing modifiers acting on A-1 bulged 5′-splice sites reveals rules for rational drug design
Authors: Malard Florian , Wolter Antje C , Marquevielle Julien , Morvan Estelle , Ecoutin Agathe , Rüdisser Simon H , Allain Frédéric H T , Campagne Sebastien
Published: March 2024

Pharmacological modulation of RNA splicing by small molecules is an emerging facet of drug discovery. In this context, the SMN2 splicing modifier SMN-C5 was used as a prototype to understand the mode of action of small molecule splicing modifiers and propose the concept of 5′-splice site bulge repair. In this study, we combined in vitro binding assays and structure determination by NMR spectroscopy to identify the binding modes of four other small molecule splicing modifiers that switch the splicing of either the SMN2 or the HTT gene. Here, we determined the solution structures of risdiplam, branaplam, SMN-CX and SMN-CY bound to the intermolecular RNA helix epitope containing an unpaired adenine within the G-2A-1G+1U+2 motif of the 5′-splice site. Despite notable differences in their scaffolds, risdiplam, SMN-CX, SMN-CY and branaplam contact the RNA epitope similarly to SMN-C5, suggesting that the 5′-splice site bulge repair mechanism can be generalised. These findings not only deepen our understanding of the chemical diversity of splicing modifiers that target A-1 bulged 5′-splice sites, but also identify common pharmacophores required for modulating 5′-splice site selection with small molecules.
Pulsed operation of perovskite LEDs: a study on the role of mobile ions
Authors: Torre Cachafeiro Miguel A , Kumawat Naresh Kumar , Gao Feng , Tress Wolfgang
Published: March 2024

Metal halide perovskite light-emitting diodes (PeLEDs) are a promising technology for energy-efficient and cost-effective lighting and displays, thanks to their tunable color emission, high brightness, color purity and low-temperature fabrication. However, the mixed ionic-electronic conductivity of perovskite materials presents unique challenges, as ionic defects can redistribute under operation, affecting the energy landscape and charge recombination mechanisms. Our drift-diffusion simulations establish a connection between the transient electroluminescence (TrEL) signals of PeLEDs under pulsed operation and the influence of mobile ions. We find that the TrEL plateau value’s dependence on the duty cycle and end-of-pulse overshoot can be explained by the time-varying distribution of ionic defects. The inclusion of mobile ions is crucial to understand the TrEL response. Moreover, the simulations highlight injection barriers at the perovskite/charge-transport layer interfaces, such as is the case for the hole transport layer in our example, as a significant source of non-radiative charge recombination. These findings contribute to the understanding of transient ionic processes in perovskite-based devices.
Tax and Globalisation: Toward a New Social Contract
Authors: Dagan Tsilly
Published: March 2024

Taxation and representation are famously linked in the coercive co-authored project of political governance described through the social contract metaphor. Globalisation transforms this canonical account of the state. Many people can relocate and operate beyond state borders, consuming goods and services publicly offered by other jurisdictions. Expanding people’s opportunities to satisfy their preferences and pursue their goals supports their liberty. Yet, it also limits the ability of states to collect taxes so as to provide necessary public goods and secure justice, jeopardising the bond between taxation and equal membership in a political community. The challenge for taxation under globalisation is to revitalise the very basis of the social contract. Ideally, the new social contract should support the states’ just institutions and the collective self-determination of their members without rolling back the opportunities people have acquired through globalisation.
Correction to: Generalization of Hamiltonian mechanics to a three-dimensional phase space
Authors: Sato Naoki
Published: March 2024

In a recent paper [N. Sato, Prog. Theor. Exp. Phys. 2021, 6, 063A01 (2021)] we introduced a generalization of Hamiltonian mechanics to three-dimensional phase spaces in terms of closed 3-forms. This correction addresses an error in the proof of theorem 3, which concerns the existence of a coordinate change transforming a closed 3-form into a constant form. Indeed, invertibility of a 3-form is not sufficient to ensure the existence of a solution Xt to eq. (77) when n > 3. The theorem can be corrected by restricting the class of 3-forms to those that are relevant to generalized Hamiltonian mechanics. Although the new theorem requires a stronger hypothesis, the formulation of dynamical systems with 2 invariants in terms of closed 3-forms, which is the key contribution of the paper, holds.
Create your own path: social cerebellum in sequence-based self-guided navigation
Authors: Li Meijia , Haihambo Naem , Bylemans Tom , Ma Qianying , Heleven Elien , Baeken Chris , Baetens Kris , Deroost Natacha , Van Overwalle Frank
Published: March 2024

Spatial trajectory planning and execution in a social context play a vital role in our daily lives. To study this process, participants completed a goal-directed task involving either observing a sequence of preferred goals and self-planning a trajectory (Self Sequencing) or observing and reproducing the entire trajectory taken by others (Other Sequencing). The results indicated that in the observation phase, witnessing entire trajectories created by others (Other Sequencing) recruited cerebellar mentalizing areas (Crus 2 and 1) and cortical mentalizing areas in the precuneus, ventral and dorsal medial prefrontal cortex and temporo-parietal junction more than merely observing several goals (Self Sequencing). In the production phase, generating a trajectory by oneself (Self Sequencing) activated Crus 1 more than merely reproducing the observed trajectories from others (Other Sequencing). Additionally, self-guided observation and planning (Self Sequencing) activated the cerebellar lobules IV and VIII more than Other Sequencing. Control conditions involving non-social objects and non-sequential conditions where the trajectory did not have to be (re)produced revealed no differences with the main Self and Other Sequencing conditions, suggesting limited social and sequential specificity. These findings provide insights into the neural mechanisms underlying trajectory observation and production by the self or others during social navigation.
The first insight into Mycobacterium tuberculosis complex isolates in the lower northern region in Thailand
Authors: Rudeeaneksin Janisara , Bunchoo Supranee , Phetsuksiri Benjawan , Srisungngam Sopa , Khummin Ratchaneeporn , Thapa Jeewan , Nakajima Chie , Suzuki Yasuhiko
Published: March 2024

Background

Tuberculosis (TB) remains an important infectious disease and different genotypes have been reported. This study aimed to investigate the genetic diversity and molecular epidemiology of TB in the lower northern region of Thailand, where genotyping data are limited.

Methods

A total of 159 Mycobacterium tuberculosis complex (MTBC) isolates from this region were genotyped by spoligotyping and the major spoligotypes were further subdivided by the mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) method.

Results

Spoligotyping identified 34 types and classified them into 14 clusters. East African–Indian (EAI) groups were the most frequent (44.7%), followed by Beijing (36.5%), with a higher prevalence of drug resistance. By 15-loci MIRU-VNTR typing, the major groups of the Beijing and EAI2_NTB were further differentiated into 44 and 21 subtypes forming 9 and 5 subclusters with cluster rates of 0.26 and 0.44, respectively. The Hunter–Gaston Discriminatory Index among the Beijing and EAI2_NTB groups were 0.987 and 0.931, respectively, indicating high diversity.

Conclusions

This is the first look at the MTBC genotypes in the lower northern region of Thailand, which could aid in understanding the distribution and potential spread of MTBC and Mycobacterium bovis in the target region to support TB control in Thailand.
Predictors of 28-day mortality in melioidosis patients presenting to an emergency department: a retrospective cohort study from South India
Authors: Nisarg S , Tirlangi Praveen Kumar , Ravindra Prithvishree , Bhat Rachana , Sujir Sachin Nayak , Alli Sai Deepak , Chowdhury Soumi , Earny Venkat Abhiram , Gupta Nitin , Mukhopadhyay Chiranjay
Published: March 2024

Background

Septic melioidosis is associated with high mortality in resource-limited settings. The current study aims to find 28-d all-cause mortality predictors within 24 h of admission in melioidosis patients presenting to an emergency department.

Methods

This retrospective cohort study (2018–2022) included melioidosis patients divided into two groups based on their primary outcomes (28-d mortality). All the clinically relevant factors significant in univariate analysis were selected for binary logistic regression analysis. Those factors significant in logistic regression analysis were considered independent predictors of mortality.

Results

Of the 53 patients with melioidosis, the 28-d mortality of melioidosis patients admitted to the emergency department was 51% (n=27). Respiratory involvement, renal dysfunction, haemodynamic instability, elevated aspartate transaminase, elevated activated partial thromboplastin time, elevated CRP, elevated procalcitonin, decreased albumin, decreased absolute neutrophil count, decreased absolute lymphocyte count and use of piperacillin-tazobactam or azithromycin were significant predictors of mortality on univariate analysis. Vasopressor requirement (p=0.03) and low serum albumin level (0.041) at presentation were independent predictors of mortality.

Conclusion

Vasopressor requirement and low albumin levels at presentation in the emergency department are independent predictors of mortality. There is a need to create awareness among primary care physicians to enable early diagnosis and prompt initiation of treatment.
Tonic dendritic GABA release by substantia nigra dopaminergic neurons
Authors: Simmons DeNard V , Moreno-Ramos Oscar Andrés , Raj Divya D.A. , Kaganovsky Konstantin , Ding Jun , Awatramani Rajeshwar , Wilson Charles J. , Surmeier D. James
Published: March 2024

Recent studies have demonstrated the importance of extrastriatal dopamine release in the emergence of the network dysfunction underlying motor deficits in Parkinson’s disease (PD). To better characterize the actions of dopamine on substantia nigra pars reticulata (SNr) GABAergic neurons, optogenetic and electrophysiological tools were used inex vivomouse brain slices to monitor synaptic transmission arising from globus pallidus externa (GPe) neurons. As predicted by previous work, activation of D2 dopamine receptors (D2Rs) suppressed GABA release evoked by stimulation of GPe axons. However, D2R activation also suppressed a tonic, GABAAreceptor-mediated inhibition of SNr spiking. D2R-mediated inhibition of tonic GABA release led to a roughly 30% increase in SNr spiking rate. Chemogenetic inhibition of GPe terminals or excitation of astrocytes did not affect tonic GABA release in the SNr. In contrast, chemogenetic inhibition of dopaminergic neurons or knocking down the expression of aldehyde dehydrogenase 1A1 (ALDH1A1) blunted tonic GABAergic signaling. Antagonizing D1 dopamine receptors on the terminals of striatonigral neurons also modestly increased SNr spiking. Lastly, in a progressive mouse model of PD targeting dopaminergic neurons, the tonic inhibition of SNr neurons by GABA release also was lost. Taken together, these observations suggest that dopamine and GABA are co-released by the dendrites of ALDH1A1-expressing dopaminergic neurons that course through the SNr. The co-release of these transmitters could serve to promote movement by making SNr neurons less responsive to phasic activity arising from the indirect pathway circuitry and by lowering basal spiking rates.
Sensory processing sensitivity is associated with neural synchrony and functional connectivity during threatening movies
Authors: Damatac Christienne G. , Homberg Judith R. , Galesloot Tessel E. , Geerligs Linda , Greven Corina U.
Published: March 2024

Sensory processing sensitivity (SPS) is an evolutionarily conserved trait describing a person’s sensitivity to subtle stimuli, their depth of processing, emotional reactivity, and susceptibility to being overwhelmed. SPS is considered a fundamental and evolutionarily conserved trait, yet its neural mechanisms remain insufficiently understood. Therefore, we investigated whether SPS relates to processing movies differently in the central executive (CEN), default mode (DMN), and salience (SN) networks. We obtained positive and negative dimension Sensory Processing Sensitivity Questionnaire (short-form) scores and (neutral and threat aural framing) movie-fMRI data from a population-based sample (Healthy Brain Study, N=238, agemean=34years). We performeda prioriinter-subject representation similarity, activation, and inter-subject functional connectivity analyses to characterize SPS-dimension-related neural responses during movie-viewing. More similar negative dimension SPS score related to more neural synchrony in the CEN and SN during threat. Higher negative dimension SPS score related to reduced CEN-DMN functional connectivity during threat, an effect shared across between-network regions but most strongly driven by reduced connectivity between right dorsomedial prefrontal cortex and left lateral prefrontal cortex. Our findings suggest that highly sensitive individuals exhibit distinct CEN differences shaping environmental perception, process threat differently, and each SPSQ-SF dimension may involve unique neurological mechanisms.