bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic X‐Ray Image Sensors Using a Medium Bandgap Polymer Donor with Low Dark Current
Authors: Ha Jong‐Woon , Eom Seung Hun , Cha Bo Kyung , Song Seyeong , Eun Hyeong Ju , Kim Jong H. , Park Jong Mok , Kim BongSoo , Park Byoungwook , Ko Seo‐Jin , Yoon Sung Cheol , Lee Changjin , Jung In Hwan , Hwang Do‐Hoon
Published: May 2024

The development of portable X‐ray detectors is necessary for diagnosing fractures in unconscious patients in emergency situations. However, this is quite challenging because of the heavy weight of the scintillator and silicon photodetectors. The weight and thickness of X‐ray detectors can be reduced by replacing the silicon layer with an organic photodetectors. This study presents a novel bithienopyrroledione‐based polymer donor that exhibits excellent photodetection properties even in a thick photoactive layer (~700 nm), owing to the symmetric backbone and highly soluble molecular structure of bithienopyrroledione. The ability of bithienopyrroledione‐based polymer donor to strongly suppress the dark current density (Jd ~ 10−10 A cm−2) at a negative bias (−2.0 V) while maintaining high responsivity (R = 0.29 A W−1) even at a thickness of 700 nm results in a maximum shot‐noise‐limited specific detectivity of Dsh* = 2.18 × 1013 Jones in the organic photodetectors. Printed organic photodetectors are developed by slot‐die coating for use in X‐ray detectors, which exhibit Dsh* = 2.73 × 1012 Jones with clear rising (0.26 s) and falling (0.29 s) response times upon X‐ray irradiation. Detection reliability is also proven by linear response of the X‐ray detector, and the X‐ray detection limit is 3 mA.
VA‐ECMO weaning strategy using adjusted pulse pressure by vasoactive inotropic score in AMI complicated by cardiogenic shock
Authors: Lee Bo Ram , Choi Ki Hong , Kim Eun Jin , Lee Seung Hun , Park Taek Kyu , Lee Joo Myung , Song Young Bin , Hahn Joo‐Yong , Choi Seung‐Hyuk , Gwon Hyeon‐Cheol , Cho Yang Hyun , Yang Jeong Hoon
Published: May 2024

Aims

This study evaluated how well serial pulse pressure (PP) and PP adjusted by the vasoactive inotropic score (VIS) predicted venoarterial extracorporeal membrane oxygenation (VA‐ECMO) weaning success and clinical outcomes in acute myocardial infarction complicated by cardiogenic shock (AMI‐CS) patients.

Methods and results

A total of 213 patients with AMI‐CS who received VA‐ECMO between January 2010 and August 2021 were enrolled in the institutional ECMO registry. Serial PP and VIS were measured immediately, 12, 24, and 48 h after VA‐ECMO insertion. PP adjusted by VIS was defined as PP/√VIS. The primary outcome was successful VA‐ECMO weaning. Successful weaning from VA‐ECMO was observed in 151 patients (70.9%). Immediately after VA‐ECMO insertion, PP [successful vs. failed weaning, 26.0 (15.5–46.0) vs. 21.0 (12.5–33.0), P = 0.386] and PP/√VIS [11.1 (5.1–25.0) vs. 6.0 (3.1–14.2), P = 0.118] did not differ between the successful and failed weaning groups. Serial PP and PP adjusted by VIS at 12, 24, and 48 h after VA‐ECMO insertion were significantly higher in patients with successful weaning than those with failed weaning [successful vs. failed weaning, 24.0 (4.0–38.0) vs. 12.5 (6.0–25.5), P = 0.007 for 12 h PP, and 10.1 (5.7–22.0) vs. 2.9 (1.7–5.9), P < 0.001 for 12 h PP/√VIS]. The 12 h PP/√VIS showed better discriminative function for successful weaning than 12 h PP alone [area under the curve (AUC) 0.80, 95% confidence interval (CI) 0.72–0.88, P < 0.001 vs. AUC 0.67, 95% CI 0.57–0.77, P = 0.002]. Patients with a low 12 h PP/√VIS (≤7) had higher rates of in‐hospital mortality (44.4% vs. 19.8%, P < 0.001) and 6 month follow‐up mortality (hazard ratio 2.41, 95% CI 1.49–3.90, P < 0.001) than those with a high 12 h PP/√VIS (>7).

Conclusions

PP adjusted by VIS taken 12 h following VA‐ECMO initiation can predict weaning from VA‐ECMO more successfully than PP alone, and its low value was associated with a higher risk of mortality in AMI‐CS patients.
Optimization of gate structure towards high‐sensitivity AlGaN/GaN HEMT cortisol detection
Authors: Chang Hui , Xu Boxuan , Yang Guo , Gu Zhiqi , Li Jiadong
Published: May 2024

AlGaN/GaN high electron mobility transistors (HEMTs) have been widely studied in the field of bio‐sensing due to their advantages such as high sensitivity, excellent biocompatibility, rapid response and corrosion resistance. Previously, attention was focused on the impact of width/length ratio (W/LSD) on transconductance (gm) to improve the sensitivity, however, the position of gate (LGS/LGD) also affects the sensitivity of HEMT sensors towards biosensing. Herein, we optimized the gate geometry based on the fixed gate position at LGS/LGD=3/5. Through theoretical analysis, design, and fabrication, three AlGaN/GaN HEMT devices with W/LSD ratios of 800 μm/200 μm, 800 μm/100 μm, and 800 μm/50 μm were developed, consistently maintaining LGS/LGD at 3/5 and LG/LSD at 1/5. Using cortisol as the biochemical detection target, the sensitivity, specificity, and linearity of three different gate structures of AlGaN/GaN HEMT biosensors were validated. The results indicated that with the increase of W/LSD and the decrease of LG, the sensitivity of the three AlGaN/GaN HEMT devices significantly improved, reaching 0.455 μA dec−1, 0.880 μA dec−1, and 2.316 μA dec−1, respectively. The device with W/LSD=800 μm/50 μm and LG=10 μm showed a sensitivity approximately 5 times that of the device with W/LSD=800 μm/200 μm and LG=40 μm, and about 2.6 times that of the device with W/LSD=800 μm/100 μm and LG=20 μm, thereby validating the correctness of the theoretical calculations. Moreover, the fabricated HEMT devices were capable of detecting cortisol concentrations ranging from 10 fM to 100 μM in 1×PBS, demonstrating specificity to cortisol and good linearity, with R2 values of 0.98456, 0.98038, and 0.99232, respectively. The detection results verified the outcomes of theoretical analysis. This paper systematically investigates the integration of theoretical analysis with the practical application of AlGaN/GaN HEMT devices, providing a new method to enhance sensitivity in biochemical detection using HEMT devices.
Experimental study and multi‐scale refinement model of high damping acrylic polymer matrix VEDs for civil structural seismic retrofit
Authors: Dong Yao‐Rong , Xu Zhao‐Dong , Zhu Lihua , Shi Qingxuan , Li Qiang‐Qiang , He Jia‐Xuan , Cheng Yu
Published: May 2024

The viscoelastic dampers (VEDs), which can provide both stiffness and damping, have been recently introduced into the field of structural vibration control for seismic enhancement of civil engineering structures. In this study, a kind of high damping acrylic polymer matrix VEDs (HDPVED) is developed independently, and this innovative HDPVED can solve the significant problem of service performance under medium‐high temperature environments, as well as low‐frequency vibration control under earthquake actions for civil engineering structures. To systematically investigate the influencing rules of frequency, temperature, and displacement amplitude on the mechanical properties and damping dissipation performance of HDPVEDs, a series of dynamic mechanical performance tests of the developed HDPVEDs are carried out at different frequencies, temperatures, and displacement amplitudes. The research results show that HDPVED exhibits excellent damping dissipation capability and adaptability under medium‐high temperature environments and low‐frequency excitations. The mechanical properties and energy dissipation performance present a strong correlation with frequency, temperature and displacement amplitude, and there is an obvious coupling effect between the three influencing factors. Based on the macroscopic mechanical property research of HDPVED, the microscopic damping mechanism and microscopic mechanical properties of HDPVED are then investigated. High‐order fractional derivative fraction Voigt and Maxwell model in parallel (FVMP) models are preferred to characterize the combined hyper‐elasticity and viscoelasticity owned by networked molecular chains and free molecular chains. The breaking and reconstruction theory of microphysical bonds is used to assess the effect of packing particles, and the time‐temperature equivalence principle is introduced to assess the effect of temperature. The multi‐scale refinement model is proposed, and the validity and accuracy of this model are verified by testing data of HDPVED. The study results show that the proposed model can accurately describe the effects of frequency, temperature, displacement amplitude, and microstructure on the multi‐scale mechanical properties of HDPVED. It provides a theoretical basis for the multi‐scale design and development of high damping VEDs.
Can Bees Detect Perfluorooctane Sulfonate (PFOS)?
Authors: Sonter Carolyn A. , Tighe Matthew , Rader Romina , Wilson Susan C.
Published: May 2024

The European honey bee (Apis mellifera) is an important crop pollinator threatened by multiple stressors, including exposure to contaminants. Perfluorooctane sulfonate (PFOS) is a persistent global contaminant that accumulates and biomagnifies in food chains and is detected in honey. Even sublethal exposure to PFOS is detrimental to bee health, but exposure routes are unclear and nothing is known about bee response (detection, avoidance, or attraction) to PFOS. Using Y-mazes, we studied the response of individual bees to PFOS-spiked sugar syrup at four concentrations, 0.02, 30, 61 and 103 µg L−1. Bee activity, choice behavior, and drink duration for unspiked and spiked sugar syrup was recorded for 10 min in the Y-maze system. Most bees (≥80%) tasted and then drank the sugar syrup solutions, including the PFOS-contaminated syrup. Only at 61 and 103 µg L−1 did bees significantly avoid drinking PFOS-spiked syrup, and only when given a choice with unspiked syrup. When the choice of consuming unspiked syrup was removed, the bees drank PFOS-spiked syrup at all the PFOS concentrations tested, and avoidance was not evident. Avoidance was not observed in any treatment at 0.02 or 30 µg L−1 PFOS, concentrations that are frequently reported in environmental waters in contaminated areas. These findings confirm that bees will access PFOS-contaminated resources at concentrations detrimental to the colony health, and provide evidence of potential exposure pathways that may threaten crop pollination services and also human health via food chain transfer in PFOS-contaminated areas. Environ Toxicol Chem 2024;43:1638–1647. © 2024 SETAC
Delineating genotype and parent‐of‐origin effect on the phenotype in MSH6‐associated Lynch syndrome
Authors: van der Werf‐'t Lam Anne‐Sophie , Rodriguez‐Girondo Mar , Villasmil Mandy , Tops Carli M. , van Hest Liselotte , Gille Hans J. P. , Duijkers Floor A. M. , Wagner Anja , Eikenboom Ellis , Letteboer Tom G. W. , de Jong Mirjam M. , Bajwa‐ten Broeke Sanne W. , Bleeker Fonnet , Gomez Garcia Encarna B. , Dominguez‐Valentin Mev , Møller Pal , Suerink Manon , Nielsen Maartje
Published: May 2024

Background

This study investigates the potential influence of genotype and parent‐of‐origin effects (POE) on the clinical manifestations of Lynch syndrome (LS) within families carrying (likely) disease‐causing MSH6 germline variants.

Patients and Methods

A cohort of 1615 MSH6 variant carriers (310 LS families) was analyzed. Participants were categorized based on RNA expression and parental inheritance of the variant. Hazard ratios (HRs) were calculated using weighted Cox regression, considering external information to address ascertainment bias. The findings were cross‐validated using the Prospective Lynch Syndrome Database (PLSD) for endometrial cancer (EC).

Results

No significant association was observed between genotype and colorectal cancer (CRC) risk (HR = 1.06, 95% confidence interval [CI]: 0.77–1.46). Patients lacking expected RNA expression exhibited a reduced risk of EC (Reference Cohort 1: HR = 0.68, 95% CI: 0.43–1.03; Reference Cohort 2: HR = 0.63, 95% CI: 0.46–0.87). However, these results could not be confirmed in the PLSD. Moreover, no association was found between POE and CRC risk (HR = 0.78, 95% CI: 0.52–1.17) or EC risk (Reference Cohort 1: HR = 0.93, 95% CI: 0.65–1.33; Reference Cohort 2: HR = 0.8, 95% CI: 0.64–1.19).

Discussion and Conclusion

No evidence of POE was detected in MSH6 families. While RNA expression may be linked to varying risks of EC, further investigation is required to explore this observation.
Genomic profiling of pleomorphic rhabdomyosarcoma reveals a genomic signature distinct from that of embryonal rhabdomyosarcoma
Authors: Saoud Carla , Dermawan Josephine K. , Sharma Aarti E. , Tap William , Wexler Leonard H. , Antonescu Cristina R.
Published: May 2024

Pleomorphic rhabdomyosarcoma (PRMS) is a rare and highly aggressive sarcoma, occurring mostly in the deep soft tissues of middle‐aged adults and showing a variable degree of skeletal muscle differentiation. The diagnosis is challenging as pathologic features overlap with embryonal rhabdomyosarcoma (ERMS), malignant Triton tumor, and other pleomorphic sarcomas. As recurrent genetic alterations underlying PRMS have not been described to date, ancillary molecular diagnostic testing is not useful in subclassification. Herein, we perform genomic profiling of a well‐characterized cohort of 14 PRMS, compared to a control group of 23 ERMS and other pleomorphic sarcomas (undifferentiated pleomorphic sarcoma and pleomorphic liposarcoma) using clinically validated DNA‐targeted Next generation sequencing (NGS) panels (MSK‐IMPACT). The PRMS cohort included eight males and six females, with a median age of 53 years (range 31–76 years). Despite similar tumor mutation burdens, the genomic landscape of PRMS, with a high frequency of TP53 (79%) and RB1 (43%) alterations, stood in stark contrast to ERMS, with 4% and 0%, respectively. CDKN2A deletions were more common in PRMS (43%), compared to ERMS (13%). In contrast, ERMS harbored somatic driver mutations in the RAS pathway and loss of function mutations in BCOR, which were absent in PRMS. Copy number variations in PRMS showed multiple chromosomal arm‐level changes, most commonly gains of chr17p and chr22q and loss of chr6q. Notably, gain of chr8, commonly seen in ERMS (61%) was conspicuously absent in PRMS. The genomic profiles of other pleomorphic sarcomas were overall analogous to PRMS, showing shared alterations in TP53, RB1, and CDKN2A. Overall survival and progression‐free survival of PRMS were significantly worse (p < 0.0005) than that of ERMS. Our findings revealed that the molecular landscape of PRMS aligns with other adult pleomorphic sarcomas and is distinct from that of ERMS. Thus, NGS assays may be applied in select challenging cases toward a refined classification. Finally, our data corroborate the inclusion of PRMS in the therapeutic bracket of pleomorphic sarcomas, given that their clinical outcomes are comparable.
A perspective on the worst ever dengue outbreak 2023 in Bangladesh: What makes this old enemy so deadly, and how can we combat it?
Authors: Sarker Rapty , Roknuzzaman A. S. M. , Emon Faisal Abdullah , Dewan Syed Masudur Rahman , Hossain Md. Jamal , Islam Md. Rabiul
Published: May 2024

Background and Aims

Bangladesh has been going through outbreaks of dengue fever cases every year since 2000. Yet this year's (2023) episode of dengue fever has crossed every line concerning fatality. Symptoms of the fever range from high fever, headaches, and muscle aches to deadly dengue hemorrhagic fever (DHF). The present review aims to assess the current pathogenicity and associated risk factors of recent dengue outbreaks in Bangladesh.

Methods

To perform this review work, we extracted relevant information from published articles available in PubMed, Scopus, and Google Scholar. We used dengue virus, dengue fever, and dengue outbreaks as keywords while searching for information.

Results

This Aedes mosquito‐transmitted viral fever is more common in Bangladesh because of the tropical nature and immense burden of populations, resulting in convenient conditions for the reproduction of the vector. The rapid genetic transformation of this RNA virus and the resistance of its vector against insecticides have intensified the situation. The number of hospitalized patients has increased, and the case fatality rate has risen to 0.47%. Inadequate mosquito control measures, plenty of vector breeding sites, and a lack of public awareness have worsened the situation. Routine spraying of effective insecticides in high‐risk zones, regular inspection of potential mosquito breeding sites, and public awareness campaigns are the keys to limiting the spread of this virus. Also, the availability of detection kits, improved hospital settings, and trained health professionals are mandatory to keep disease fatalities under control.

Conclusion

Dengue fever is a preventable disease. The successful development of a competent vaccine is now a prime need for preventing any future upsurge of the disease. Also, we recommend public awareness, vector control activities, and global collaboration to prevent spread.
Factors affecting firm‐level job cuts during the COVID‐19 pandemic: A cross‐country evidence
Authors: Sarker Bibhuti
Published: May 2024

This study investigates the determinants of firms' job‐cut decisions during the COVID‐19 pandemic, considering both firm‐level and country‐level factors. Data from 31 countries (a mix of developed and emerging) collected between May 2020 and May 2021 are analyzed using a multilevel Zero‐Inflated Negative Binomial (ZINB) model. The results reveal that firms that were operational, larger in size, received financial incentives, and arranged remote work for their workforce laid off a smaller proportion of workers. Conversely, firms that experienced significant sales reductions, input supply disruptions, and introduced delivery or carry‐out services laid off a larger proportion of workers. Moreover, among financial incentive‐recipient firms, smaller ones and those that introduced remote work and delivery or carry‐out services had smaller layoffs. At the country level, the human capital index (HCI) significantly influenced job‐cut decisions, with higher HCI scores associated with smaller layoffs. Classifying countries into “developed” and “emerging” yielded similar results, except for temporary closure having no significant impact on job cuts in developed countries and remote work showing no impact on job cuts in emerging countries. The robustness of the results was confirmed by a multilevel zero‐inflated Tobit model, which consistently reproduced the outcomes.
PHLDA2 overexpression facilitates senescence and apoptosis via the mitochondrial route in human nucleus pulposus cells by regulating Wnt/β‐catenin signalling pathway
Authors: Chang Xian , Cao Ya , Hu Zhi‐Lei , Zhai Yu , Zhang Yu‐Yao , Lv Yang‐Fan , Li Chang‐Qing
Published: May 2024

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA‐β‐galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC‐1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL‐1β‐treated NPCs. JC‐1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen‐II expression and suppressed MMP3 expression in NPCs by repressing wnt/β‐catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL‐1β‐induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/β‐catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies.
Interplay of RUNX2 and KLF4 in initial commitment of odontoblast differentiation
Authors: Gao Yongyan , Lin Yuxiu , Li Yuanyuan , Zeng Wenrui , Chen Zhi
Published: May 2024

Odontoblast differentiation is a key process in dentin formation. Mouse dental papilla cells (mDPCs) are pivotal in dentinogenesis through their differentiation into odontoblasts. Odontoblast differentiation is intricately controlled by transcription factors (TFs) in a spatiotemporal manner. Previous research explored the role of RUNX2 and KLF4 in odontoblast lineage commitment, respectively. Building on bioinformatics analysis of our previous ATAC‐seq profiling, we hypothesized that KLF4 potentially collaborates with RUNX2 to exert its biological role. To investigate the synergistic effect of multiple TFs in odontoblastic differentiation, we first examined the spatiotemporal expression patterns of RUNX2 and KLF4 in dental papilla at the bell stage using immunostaining techniques. Notably, RUNX2 and KLF4 demonstrated colocalization in preodontoblast. Further, immunoprecipitation and proximity ligation assays verified the interaction between RUNX2 and KLF4 in vitro. Specifically, the C‐terminus of RUNX2 was identified as the interacting domain with KLF4. Functional implications of this interaction were investigated using small hairpin RNA‐mediated knockdown of Runx2, Klf4, or both. Western blot analysis revealed a marked decrease in DSPP expression, an odontoblast differentiation marker, particularly in the double knockdown condition. Additionally, alizarin red S staining indicated significantly reduced mineralized nodule formation in this group. Collectively, our findings highlight the synergistic interaction between RUNX2 and KLF4 in promoting odontoblast differentiation from mDPCs. This study contributes to a more comprehensive understanding of the regulatory network of TFs governing odontoblast differentiation.
Nomogram Based on High‐Resolution Vessel Wall MRI Features to Differentiate Moyamoya Disease From Atherosclerosis‐Associated Moyamoya Vasculopathy
Authors: Chong Zhen , Zhang Shujun , Yue Xiuzheng , Wang Weiwei , Liu Deguo , Yu Hao , Sun Zhanguo , Guo Xiang , Chen Yueqin , Hou Lihua
Published: May 2024

Background

The angiographic features of moyamoya disease (MMD) and atherosclerosis‐associated moyamoya vasculopathy (AS‐MMV) are similar, but the etiology and clinical treatment strategies are different. Differentiating MMD from AS‐MMV helps to choose the appropriate treatment.

Purpose

To investigate the feasibility of a nomogram based on high‐resolution vessel wall (HR‐VWI) MRI features to differentiate MMD from AS‐MMV.

Study Type

Retrospective.

Subjects

One hundred and two patients with MMD (N = 52) or AS‐MMV (N = 50) in the training cohort (9–72 years; 54 females) and 70 patients with MMD (N = 42) or AS‐MMV (N = 28) in the validation cohort (7–69 years; 33 females).

Field Strength/Sequence

3‐T, three‐dimensional time‐of‐flight MR angiography (3D‐TOF‐MRA), spin echo high‐resolution 3D T1‐weighted imaging (3D‐T1WI), 3D T2‐weighted imaging (3D‐T2WI), and contrast‐enhanced 3D‐T1WI.

Assessment

Image assessment was performed by three neuroradiologists (with 10, 15, and 18 years of experience). Demographic characteristic and image features were evaluated and compared. Independent factors of MMD were screened to construct a nomogram model in the training cohort. The validation cohort was used to validated its generality.

Statistical Tests

Interclass correlation coefficient (ICC), kappa, t‐test, χ2 test, receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve and concordance index (C‐index). A P‐value <0.05 was considered statistically significant.

Results

Significant differences were observed between MMD and AS‐MMV in terms of age, vessel outer diameter, vessel wall thickening pattern, maximum thickness, dot sign, and anterior cerebral artery (ACA) involved. Age, outer diameter, dot sign, and ACA involved were independent factors. The C‐index was 0.886 in the training cohort and 0.859 in the validation cohort. The ROC demonstrated high diagnostic efficacy with an AUC of 0.884 in the training cohort and 0.857 in the validation cohort.

Data Conclusion

A nomogram model based on age, vessel outer diameter, dot sign and ACA involved may effectively distinguish MMD from AS‐MMV with good reliability and accuracy.

Evidence Level

4

Technical Efficacy

Stage 2
Study on the value of second‐generation sequencing technology in the clinical diagnosis of osteoarticular brucellosis
Authors: Yao Xiaowei , Zhao Guisong , Wang Lianbo , Jia Chenguang
Published: May 2024

To assess the value of next‐generation sequencing (NGS) technology in the diagnosis of osteoarticular brucellosis pathogenesis. Fifty eight patients admitted to the Department of Orthopaedics, Hebei Provincial Chest Hospital from January 2021 to January 2023 were retrospectively analyzed, and the patients were classified into 48 cases in the osteoarticular brucellosis group and 10 cases in the nonosteoarticular brucellosis group according to the final clinical diagnosis. All patients underwent serum agglutination test (SAT), CT‐guided puncture or surgical sampling of lesions for bacteriological culture and NGS after admission. The diagnostic efficacy of these three methods for osteoarticular brucellosis was compared using the final clinical diagnosis as the reference standard. Among the 58 patients with suspected osteoarticular brucellosis, 40 cases (68.97%) were positive by NGS, 33 cases (56.89%) by SAT and 10 cases (17.24%) by culture, and the differences were statistically significant (p < 0.05). Using the final clinical diagnosis as a criterion, the sensitivity of NGS, SAT, and culture for the detection of osteoarticular brucellosis was 83.33%, 62.50%, and 20.83%, respectively, the specificity was 100.00%, 70.00%, and 100.00%, the diagnostic accuracy was 86.20%, 63.79%, and 34.49%, and the κ values were 0.799, 0.590, and 0.504, respectively. NGS has a high pathogen detection rate and sensitivity in the pathogenetic diagnosis of patients with osteoarticular brucellosis and can provide clinical guidance for the diagnosis and management of patients with osteoarticular brucellosis.
Lactase for infantile colic: A systematic review of randomized clinical trials
Authors: Nau Angélica Luciana , Bassan Amanda Santiago , Cezar Alessandra Bacelar , de Carlos Gabriel Assis , Deboni Mariana
Published: May 2024

Infantile colic is excessive crying for no apparent reason in an otherwise healthy infant. Although its physiopathology is not completely understood, therapies usually target gastrointestinal symptoms. This systematic review of randomized controlled trials (RCTs) analyzes the efficacy of lactase supplementation in infantile colic. PubMed, Embase, and Cochrane were searched for RCTs evaluating lactase supplementation in infants up to 6 months old with infantile colic. Out of six RCTs including 394 patients, three reported a significantly shorter crying time in the lactase group than in the placebo group, while the other three found no significant difference between groups. Of the two studies that performed the hydrogen breath test, only one reported a significant reduction in exhaled hydrogen levels. The pharmacological approach to infantile colic remains debatable, and new studies with standardized diagnostic criteria and outcomes are required to guide lactase supplementation in clinical practice.
Transcriptome Analysis of Left Versus Right Intrinsic Laryngeal Muscles Associated with Innervation
Authors: Kemfack Angela M. , Hernandez‐Morato Ignacio , Moayedi Yalda , Pitman Michael J.
Published: May 2024

Objectives/Hypothesis

Recurrent laryngeal nerve injury diagnosed as idiopathic or due to short‐term surgery‐related intubation exhibits a higher incidence of left‐sided paralysis. While this is often attributed to nerve length, it is hypothesized there are asymmetric differences in the expression of genes related to neuromuscular function that may impact reinnervation and contribute to this laterality phenomenon. To test this hypothesis, this study analyzes the transcriptome profiles of the intrinsic laryngeal muscles (ILMs), comparing gene expression in the left versus right, with particular attention to genetic pathways associated with neuromuscular function.

Study Design

Laboratory experiment.

Methods

RNA was extracted from the left and right sides of the rat posterior cricoarytenoid (PCA), lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA), respectively. After high‐throughput RNA‐Sequencing, 88 samples were organized into 12 datasets according to their age (P15/adult), sex (male/female), and muscle type (PCA/LTA/MTA). A comprehensive bioinformatics analysis was conducted to compare the left‐right ILMs across different conditions.

Results

A total of 774 differentially expressed genes were identified across the 12 experimental groups, revealing age, sex, and muscle‐specific differences between the left versus right ILMs. Enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways implicated several genes with a left‐right laryngeal muscle asymmetry. These genes are associated with neuronal and muscular physiology, immune/inflammatory response, and hormone control.

Conclusion

Bioinformatics analysis confirmed divergent transcriptome profiles between the left‐right ILMs. This preliminary study identifies putative gene targets that will characterize ILM laterality.

Level of Evidence

N/A Laryngoscope, 134:3741–3753, 2024
SiN‐On‐SOI Optical Phased Array LiDAR for Ultra‐Wide Field of View and 4D Sensing
Authors: Chen Baisong , Li Yingzhi , Xie Qijie , Na Quanxin , Tao Min , Wang Ziming , Zhi Zihao , Hu Heming , Li Xuetong , Qu Huan , He Yafang , Hu Xiaolong , Lo Guoqiang , Song Junfeng
Published: May 2024

3D imaging techniques are facilitating autonomous vehicles to build intelligent systems. Optical phased arrays (OPAs) featured by all solid‐state configurations are becoming a promising solution for 3D imaging. However, the majority of state‐of‐art OPAs commonly suffer from severe power degradation at the edge of the field of view (FoV), resulting in limited effective FoV and deteriorating 3D imaging quality. Here, the chained grating antenna and the vernier concept is synergized to design a novel OPA for realizing a record wide 160°‐FoV 3D imaging. By virtue of the chained antenna, the OPA exhibits less than 3‐dB beam power variation within the 160°FoV. In addition, two OPAs with different pitches are integrated monolithically to form a quasi‐coaxial Vernier OPA transceiver. With the aid of a flat beam power profile provided by the chained antennas, the OPA exhibits uniform beam quality at an arbitrary steering angle. The superior beam steering performance enables the OPA to accomplish 160° wide‐FoV 3D imaging based on the frequency‐modulated continuous‐wave (FMCW) LiDAR scheme. The ranging accuracy is 5.5‐mm. Moreover, the OPA is also applied to velocity measurement for 4D sensing. To the best of knowledge, it is the first experimental implementation of a Vernier OPA LiDAR on 3D imaging to achieve a remarkable FoV.
Patient‐ and caregiver‐reported impact of symptoms in Duchenne muscular dystrophy
Authors: Rosero Spencer , Weinstein Jennifer , Seabury Jamison , Varma Anika , Dilek Nuran , Zizzi Christine , Coffey Madeleine , Greco Brittany , Heatwole John , Alexandrou Danae , Guntrum Debra , Ciafaloni Emma , Heatwole Chad
Published: May 2024

Introduction/Aims

To better understand the disease burden faced by individuals with Duchenne muscular dystrophy (DMD) of all ages and elucidate potential targets for therapeutics, this study determined the prevalence and relative importance of symptoms experienced by individuals with DMD and identified factors associated with a higher disease burden.

Methods

We conducted qualitative interviews with individuals with DMD and caregivers of individuals with DMD to identify potential symptoms of importance to those living with DMD. We subsequently performed a cross‐sectional study to assess which symptoms have the highest prevalence and importance in DMD and to determine which factors are associated with a higher disease burden.

Results

Thirty‐nine individuals, aged 11 years and above, provided 3262 quotes regarding the symptomatic burden of DMD. Two hundred participants (87 individuals with DMD and 113 caregivers) participated in a subsequent cross‐sectional study. Individuals with DMD identified limitations with mobility or walking (100%), inability to do activities (98.9%), trouble getting around (97.6%), and leg weakness (97.6%) as the most prevalent and life altering symptomatic themes in DMD. The symptomatic themes with the highest prevalence, as reported by caregivers on behalf of those with DMD for whom they care, were limitations with mobility or walking (90.3%), leg weakness (89.2%), and emotional issues (79.6%). Steroid/glucocorticoid use (e.g., prednisone or deflazacort) was associated with a lower level of disease burden in DMD.

Discussion

There are many symptomatic themes that contribute to disease burden in individuals with DMD. These symptoms are identified by both individuals with DMD and their caregivers and have a variable level of importance and prevalence in the DMD population.
Fully bio‐based flax/furan versus carbon/glass epoxy composites: Scope and limitations in terms of fire and physico‐mechanical performances
Authors: Kandola Baljinder K. , Pornwannachai Wiwat , Weclawski Bartosz , Ebdon John R.
Published: May 2024

Fire and mechanical performances of a bio‐based flax/furan resin composite are evaluated and, in order to assess their commercial potential, compared with those of conventional carbon/glass fiber‐reinforced composites. Fire retardant (FR) variants of flax/furan were obtained by adding FRs to the resin and using (i) flax or (ii) FR‐treated flax fabrics. With (i), the fire hazard of the composite could be reduced to minimum, without detrimental effect on the mechanical properties. However, use of FR‐flax fabric (ii) led to impairment of mechanical properties. This indicated that for optimized fire and mechanical properties, use of a FR in the resin matrix suffices; there is no advantage in using a FR‐treated flax fabric. Natural aging of the samples for 10 years followed by water aging indicated that water absorption in flax/furan composites was much higher than in comparable carbon/epoxy composites. While there was evidence of released acidic components such as acetic acid, oxalic acid, and so forth, in flax/furan composites, mainly from oxidative degradation of furan resin, there was no evidence of leaching of FR additives from the matrix. However, FR treatment of flax fabric affected the fiber–matrix interfacial adhesion, leading to considerable water absorption during aging and disintegration of the reinforcement.

Highlights

Furan resins are naturally fire retardant, burn only under forced combustion.

FR flax/furan composites obtained by adding FRs to the resin or the flax fabric.

FR treatment of the flax impairs mechanical properties and water tolerance.

FRs in the resin neither affect mechanical properties nor leach out in water.
Application of multiple validated algorithms for identifying incident breast cancer among individuals with atopic dermatitis
Authors: Campos Adriana , Ramasubramanian Ramya , Wong Cherise , Marcus Andrea Fleisch
Published: May 2024

Purpose

Validated algorithms (VAs) in insurance claims databases are often used to estimate the prevalence and incidence of comorbidities and evaluate safety signals. However, although they are then used in different data sources or subpopulations from those in which they were developed the replicability of these VAs are rarely tested, making their application and performance in these settings potentially unknown. This paper describes testing multiple VAs used to identify incident breast cancer cases in a general population and in an indication‐specific population, patients with atopic dermatitis (AD).

Methods

Two algorithms were tested in multiple insurance claims databases and four cohorts were created. Modifications were made to account for the US insurance setting. The resulting incidence rates (IRs) were then compared across algorithms and against surveillance, epidemiology, and end results (SEER) estimates to assess reliability.

Results

Algorithm 1 produced low IRs compared to Algorithm 2. Algorithm 2 provided similar estimates to those of SEER. Individuals in the AD cohorts experienced lower incident breast cancer cases than those in the general population cohorts.

Conclusion

Regardless of an algorithm's reported accuracy, the original study setting and targeted population for the VAs may matter when attempting to replicate the algorithm in an indication‐specific subpopulation or varying data sources. Investigators should use caution and conduct sensitivity analyses or use multiple algorithms when attempting to calculate incidence or prevalence estimates using VAs.
Do efficacy results obtained from randomized controlled trials translate to effectiveness data from observational studies for relapsing–remitting multiple sclerosis?
Authors: Verweij Stefan , Ahmed Wouter , Zhou Guiling , Mavridis Dimitris , Nikolakopoulos Stavros , Elferink Andre J. , Rengerink Katrien Oude , Bijlsma Maarten J. , Mol Peter G. M. , Hak Eelko
Published: May 2024

Background

Randomized controlled trials are considered the gold standard in regulatory decision making, as observational studies are known to have important methodological limitations. However, real‐world evidence may be helpful in specific situations. This review investigates how the effect estimates obtained from randomized controlled trials compare to those obtained from observational studies, using drug therapy for relapsing–remitting multiple sclerosis as an example.

Study Design and Setting

A systematic review of randomized controlled trials and observational studies was conducted. The primary outcome was the annualized relapse rate. Using (network) meta‐analysis together with posterior predictive distributions, the drug‐specific rate ratios from the network of randomized controlled trials were compared with those from the network of observational studies.

Results

Effect estimates from 26 observational studies showed greater magnitudes and were less precise compared to estimates obtained from 21 randomized controlled trials. Twenty of the 28 treatment comparisons between designs had similar rate ratios. Seven inconsistencies in observed rate ratios could be attributed to two specific disease‐modifying therapies.

Conclusion

In this case study, estimates from observational studies predominantly agreed with estimates from randomized controlled trials given their posterior predictive distributions. Multiple observational studies together may therefore supplement additional pivotal randomized controlled trials in relapsing–remitting multiple sclerosis, for instance facilitating the extrapolation of trial results to the broader patient population.
Numerical simulation on cellular structure and mechanical properties of tungsten particles/polymethyl methacrylate microcellular composites
Authors: Zhu Yuxuan , Liu Zhicheng , Liu Ziran , Zhou Danfeng , Luo Guoqiang , Sun Jiuxiao , Cao Peng , Shen Qiang
Published: May 2024

Microcellular composites combine the advantages of composite material and microcellular material. Introducing the inclusion phase into the polymer matrix can optimize the cellular structure and improve the mechanical properties of microcellular materials. This paper focuses on rigid W particles reinforced PMMA microcellular materials, combining compression experiments and meso FE simulations to investigate the structure–property relationship of cellular structure and compressive properties for W/PMMA microcellular composites. The results indicate that W particles promote heterogeneous nucleation, reducing the cell size to 3 μm, and reinforce the PMMA matrix. W particles (10 → 60 wt%) are linearly and exponentially related to compressive modulus and compressive strength of W/PMMA microcellular composites, increased by 49.3% and 19.8%. Void porosity (71% → 48%) is quadratic related to compressive properties of W/PMMA microcellular composites, increased by 109%. Cell sizes (5 → 1 μm, especially smaller than the W particle sizes) are exponentially related to compressive properties of W/PMMA microcellular composites, increased by 38.5%. This work provides theoretical support for the regulation of cellular structure and optimization of mechanical properties of microcellular materials.
Analysis of the homodimeric structure of a D‐Ala‐D‐Ala metallopeptidase, VanX, from vancomycin‐resistant bacteria
Authors: Konuma Tsuyoshi , Takai Tomoyo , Tsuchiya Chieko , Nishida Masayuki , Hashiba Miyu , Yamada Yudai , Shirai Haruka , Motoda Yoko , Nagadoi Aritaka , Chikaishi Eriko , Akagi Ken‐ichi , Akashi Satoko , Yamazaki Toshio , Akutsu Hideo , Ikegami Takahisa
Published: May 2024

Bacteria that have acquired resistance to most antibiotics, particularly those causing nosocomial infections, create serious problems. Among these, the emergence of vancomycin‐resistant enterococci was a tremendous shock, considering that vancomycin is the last resort for controlling methicillin‐resistant Staphylococcus aureus. Therefore, there is an urgent need to develop an inhibitor of VanX, a protein involved in vancomycin resistance. Although the crystal structure of VanX has been resolved, its asymmetric unit contains six molecules aligned in a row. We have developed a structural model of VanX as a stable dimer in solution, primarily utilizing nuclear magnetic resonance (NMR) residual dipolar coupling. Despite the 46 kDa molecular mass of the dimer, the analyses, which are typically not as straightforward as those of small proteins around 10 kDa, were successfully conducted. We assigned the main chain using an amino acid‐selective unlabeling method. Because we found that the zinc ion‐coordinating active sites in the dimer structure were situated in the opposite direction to the dimer interface, we generated an active monomer by replacing an amino acid at the dimer interface. The monomer consists of only 202 amino acids and is expected to be used in future studies to screen and improve inhibitors using NMR.
Structural and functional insights into transcription activation of the essential LysR‐type transcriptional regulators
Authors: Shi Jing , Feng Zhenzhen , Song Qian , Wang Fulin , Zhang Zhipeng , Liu Jian , Li Fangfang , Wen Aijia , Liu Tianyu , Ye Zonghang , Zhang Chao , Das Kalyan , Wang Shuang , Feng Yu , Lin Wei
Published: May 2024

The enormous LysR‐type transcriptional regulators (LTTRs), which are diversely distributed amongst prokaryotes, play crucial roles in transcription regulation of genes involved in basic metabolic pathways, virulence and stress resistance. However, the precise transcription activation mechanism of these genes by LTTRs remains to be explored. Here, we determine the cryo‐EM structure of a LTTR‐dependent transcription activation complex comprising of Escherichia coli RNA polymerase (RNAP), an essential LTTR protein GcvA and its cognate promoter DNA. Structural analysis shows two N‐terminal DNA binding domains of GcvA (GcvA_DBD) dimerize and engage the GcvA activation binding sites, presenting the −35 element for specific recognition with the conserved σ70R4. In particular, the versatile C‐terminal domain of α subunit of RNAP directly interconnects with GcvA_DBD, σ70R4 and promoter DNA, providing more interfaces for stabilizing the complex. Moreover, molecular docking supports glycine as one potential inducer of GcvA, and single molecule photobleaching experiments kinetically visualize the occurrence of tetrameric GcvA‐engaged transcription activation complex as suggested for the other LTTR homologs. Thus, a general model for tetrameric LTTR‐dependent transcription activation is proposed. These findings will provide new structural and functional insights into transcription activation of the essential LTTRs.
N‐Butylpyrrolidinone is an equally good solvent as N,N‐dimethylformamide for microwave assisted solid phase peptide synthesis
Authors: Öhlander Andrea , Lüdtke Carsten , Sahakjan Artur , Johnsson Richard E.
Published: May 2024

Solid‐phase peptide synthesis (SPPS) is the prevailing method for synthesizing research peptides today. However, SPPS is associated with a significant environmental concern due to the utilization of hazardous solvents such as N,N‐dimethylformamide (DMF) or N‐methylpyrrolidone, which generate substantial waste. In light of this, our research endeavors to identify more environmentally friendly solvents for SPPS. In this study, we have assessed the suitability of five green solvents as alternatives to DMF in microwave assisted SPPS. The solvents evaluated include Cyrene, ethyl acetate, 1,3‐dioxolane, tetrahydro‐2‐methylfuran, and N‐Butylpyrrolidinone (NBP). Our investigation encompassed all stages of the synthesis process, from resin swelling, dissolution of reagents, culminating in the successful synthesis of five diverse peptides, including the challenging ACP 65–74, Peptide 18A, Thymosin α1, and Jung‐Redemann peptide. Our findings indicate that NBP emerged as a strong contender, performing on par with DMF in all tested syntheses. Furthermore, we observed that combinations of NBP with either ethyl acetate or tetrahydro‐2‐methylfuran demonstrated excellent results. This research contributes to the pursuit of more sustainable and environmentally conscious practices in peptide synthesis.
Enhanced Performance of GaN HEMTs in X‐band Applications Using SixN/Si3N4 Bilayer Passivation Technique
Authors: Li Shiming , Wu Mei , Yang Ling , Hou Bin , Zhang Meng , Chang Qingyuan , Ma Xiaohua , Hao Yue
Published: May 2024

In order to achieve high‐performance gallium nitride (GaN) high‐electron‐mobility‐transistors (HEMTs) capable of operating in the X‐band, a bilayer passivation technique is employed. The technique involves creating a stacked passivation layer consisting of a 20‐nm Si‐rich silicon nitride (SixN) passivation layer and a 100‐nm N‐rich silicon nitride (Si3N4) passivation layer. This effectively reduces radio frequency scattering in GaN HEMTs without compromising the breakdown voltage (BV). On the one hand, the SixN passivation layer effectively suppresses the surface states of devices, resulting in low current collapse. On the other hand, the Si3N4 passivation layer can effectively reduce gate leakage caused by the SixN passivation layer, allowing the device to reliably operate at higher voltages. Consequently, a GaN HEMTs with SixN/Si3N4 bilayer passivation achieve a low current collapse of 5% and a high BV of 157 V. The device features a current gain cutoff frequency (fT) and maximum oscillation frequency (fmax) of 57.9 and 96.8 GHz, respectively. Additionally, it exhibits excellent radio frequency performance in the X‐band, with an output power density (Pout) of 13.7 W mm−1 and power added efficiency of 60.8% at a drain voltage (VD) bias of 50 V.