bluuebunny/crossref_metadata_2025 huggingface dataset:
Shooting for abundance: Comparing integrated multi‐sampling models for camera trap and hair trap data
Authors: Jahid Mehnaz , Steeves Holly N. , Fisher Jason T. , Bonner Simon J. , Muthukumarana Saman , Cowen Laura L. E.
Published: September 2022

Abundance estimation is a vital goal in wildlife monitoring. Camera‐traps are a tool to survey wildlife populations noninvasively and can be used for abundance estimation if individuals are identifiable. However, for species without individual identification characteristics, camera‐trap surveys have often been combined with some other survey method such as capture‐recapture (CR, using traditional tags or DNA through hair snags or scat) to inform an integrated model. We discuss and apply two integrated models involving presence‐absence data from camera traps and CR data from hair traps to compare bias and precision to estimate the population density of grizzly bears of the central Rocky Mountains of Alberta, Canada. Unlike many other studies, we found that integrating presence‐absence data with CR data does not improve the precision of the density estimates. The possible reasons for such results are discussed in detail.
Reasonable stopping method and retracement channel support at fully mechanized top coal caving working face of 15 m extra‐thick coal seam: A case study
Authors: Xie Shengrong , Wu Yiyi , Ma Xiang , Chen Dongdong , Guo Fangfang , Jiang Zaisheng , Li Hui , Zou Hang , Liu Ruipeng , Zhang Xiao
Published: September 2022

Extra‐thick coal seams are widely distributed in the Datong mine area in China. The rapid stopping of mining and the support withdrawal technology for extra‐thick coal seams need to be developed urgently. The reasonable stopping top coal caving distance, main roof's fracture line position, and large section roadway during the stopping period (LSRSP) support method of the header face of 15 m extra‐thick coal seam are systematically studied by using field measurement, experiment, numerical simulation, and similar material simulation methods. With the increase in stopping coal caving distance, the range of the medium and low displacement zone of the LSRSP overburden gradually expands. In contrast, the depth of the plastic zone decreases. The scope and intensity of the high‐stress area of the overlying rock in front gradually decrease and shift from deep to the outside, while the peak stress area shifts from the top coal area to the coal rib of the retracement channel. Comparing the stopping of medium‐thick and thick coal seam working face, the interaction between “main roof−unmined top coal−supports” is analyzed. The unique characteristics of the extra‐thick coal seam working face are derived: when the stopping coal caving distance is shorter than the length of the key block, the dropped coal body cannot effectively restrict the movement of key blocks. Mutual compression and subsidence occur between key blocks, making the broken coal rock block squeeze into the supports. By the simulation study of each index, the stopping coal caving distance of the extra‐thick coal seam is optimal when it is slightly larger than the length of the key block (i.e., the periodic weighting step), simultaneously, the main roof fracture line behind the supports is most favorable for stopping mining. After ensuring the stability of the LSRSP's overburden structure, the differentiated support scheme of “controlled zoning−strength grading” was proposed, and the scheme was modified and verified by simulating the support prestress field. After field practice, the roof of the retracement channel is better controlled in deformation under the joint horizontal and vertical support, the robust control effect of the combined anchor cable is noticeable, the integrity of the polyurethane network is more substantial, and the working face supports have successfully achieved a safe and rapid evacuation.
Source areas of the Eastern Ebro Valley loess (NE Iberian Peninsula): Heavy mineral composition as a provenance indicator
Authors: Plata José M. , Balasch Josep Carles , Rodríguez Rafael , Boixadera Jaume , Castelltort Xavier , Olarieta José Ramón , Antúnez Montserrat , Poch Rosa M.
Published: September 2022

Loess deposits of the Eastern Ebro Valley (NE Iberian Peninsula) occupy an area of ~2000 km2 mostly on the east of the Ebro depression and locally in the Móra Basin. We studied 38 samples of loess and 47 samples of their possible source areas, in order to determine the location of the origin of the loess materials, based on their particle size distribution and composition of heavy minerals. Our results clearly differentiate two depositional loess basins disconnected by the reliefs of the Pre‐Coastal Range with different mineralogical signatures: the Ebro Basin and the Móra Basin. The most relevant variables to discern source areas were the percentage of heavy minerals, the concentrations of zircon, staurolite, rutile and inosilicates, and the presence of gypsum. In the Ebro Basin, the largest set of loess deposits is located around a depocenter in the Batea region and along several lateral areas, with materials that come from the central alluvial plain of the Middle Ebro River (25 to >100 km travel distance), in addition to deflated materials from Miocene interfluvial substrates. On the other hand, loess deposits of the Móra Basin come from more proximal source areas (<15 km), originating from the alluvial materials of the Lower Ebro River that contain the contributions of its tributaries, the Cinca and Segre rivers. Taking into account the homogeneity in the mineralogical composition of complex loess sequences, we deduced a general WNW–ESE wind direction, which would have remained constant over the last two cold periods (MIS‐2 and MIS‐6). Along this axis, the Pàndols–Cavalls Range, with a height difference of 200–350 m, acted as a wind barrier separating the loess of Ebro Basin from the loess of Móra Basin.
Spatial time index non‐orthogonal multiple access for beyond 5G wireless networks
Authors: Jayaram Madhumitha , Marchala Anjaneyulu Bhagyaveni
Published: September 2022

Multiple input multiple output (MIMO) based non‐orthogonal multiple access (NOMA) has been an evolving technique for 5G and beyond 5G wireless networks in the last decade. The goal of the proposed technique is to achieve improved spectral efficiency, with reduced complexity in the transceiver design. A novel time‐based spatial modulation‐MIMO based NOMA (SM‐MIMO‐NOMA) known as space time index‐based NOMA (STIN) has been proposed, which brings down the number of RF chains used at the transmitter end and improves the spectral efficiency in terms of bits per channel use. In the STIN algorithm, Joint GPS enabled channel estimation and threshold rate‐based power allocation are performed for user clustering and enhancing capacity. The transmit information bits are conveyed by the active antenna index as well as amplitude phase modulation by incorporating the block user‐symbol ratio at the base station. On the receiver side, user‐timeslot‐based successive interference cancellation with a maximum likelihood detector is implemented in the user equipment. STIN improves the bits per channel use with increasing modulation order and number of users by 33%. This novel algorithm has shown better performance in comparison with the existing NOMA‐based spatial modulation techniques in terms of average bit error rate, spectral efficiency, and complexity.
Nitrite‐reducing performance of two Lactobacillus strains isolated from traditional Sichuan fermented sausage in different production processes
Authors: Ji Lili , Zhou Chunyan , Ning Jia‐wen , Wang Shu , Nie Qing , Wang Wei , Zhang Jiamin , Zhao Zhiping
Published: September 2022

Two lactic acid bacteria (LAB) strains were screened in traditional Sichuan sausage, and their nitrite‐reducing performance in different production processes was determined in this study. LAB were isolated from traditional Sichuan sausages and identified by 16S rDNA sequencing. The effects of the isolated bacteria on the bacterial community, physicochemical properties, and nitrite‐decreasing capacity during sausage fermentation were investigated by comparing nonactivated treatment and activated treatment at 30°C. The results showed that the screened two LAB strains were identified as Pediococcus pentosaceus and Leuconostoc mesenteroides, which adapted well to the new habitat of fermented sausage, reaching a maximum of 7.00 and 7.32 lg CFU g−1 in the nonactivated treatment, 7.65 and 7.52 lg CFU g−1 in the activated treatment, and the two strains had strong acidizing potential, which could inhibit the growth of saprophytic bacteria. Otherwise, the activated treatment was better than the traditional process for nitrite degradation and fermentation time, except for color. Both strains contribute to nitrite consumption while reducing fermentation time and sausage production cycles. In conclusion, these two strains are expected to be the starting point for the improvement of biological safety and nitrite residue control in traditional Sichuan sausage production.
Concentration and proteolysis of CX3CL1 may regulate the microglial response to CX3CL1
Authors: Finneran Dylan , Li Qingyou , Subbarayan Meena S. , Joly‐Amado Aurelie , Kamath Siddharth , Dengler Daniela G. , Gordon Marcia N. , Jackson Michael R. , Morgan Dave , Bickford Paula C. , Smith Layton H. , Nash Kevin R.
Published: September 2022

Fractalkine (FKN) is a membrane‐bound chemokine that can be cleaved by proteases such as ADAM 10, ADAM 17, and cathepsin S to generate soluble fragments. Studies using different forms of the soluble FKN yield conflicting results in vivo. These observations prompted us to investigate the function and pharmacology of two commonly used isoforms of FKN, a human full‐length soluble FKN (sFKN), and a human chemokine domain only FKN (cdFKN). Both are prevalent in the literature and are often assumed to be functionally equivalent. We observed that recombinant sFKN and cdFKN exhibit similar potencies in a cell‐based cAMP assay, but binding affinity for CX3CR1 was modestly different. There was a 10‐fold difference in potency between sFKN and cdFKN when assessing their ability to stimulate β‐arrestin recruitment. Interestingly, high concentrations of FKN, regardless of cleavage variant, were ineffective at reducing pro‐inflammatory microglial activation and may induce a pro‐inflammatory response. This effect was observed in mouse and rat primary microglial cells as well as microglial cell lines. The inflammatory response was exacerbated in aged microglia, which is known to exhibit age‐related inflammatory phenotypes. We observed the same effects in Cx3cr1−/− primary microglia and therefore speculate that an alternative FKN receptor may exist. Collectively, these data provide greater insights into the function and pharmacology of these common FKN reagents, which may clarify conflicting reports and urge greater caution in the selection of FKN peptides for use in in vitro and in vivo studies and the interpretation of results obtained using these differing peptides.
Age‐associated sex and asymmetry differentiation in hemispheric and lobar cortical ribbon complexity across adulthood: A UK Biobank imaging study
Authors: Nazlee Nafeesa , Waiter Gordon D. , Sandu Anca‐Larisa
Published: September 2022

Cortical morphology changes with ageing and age‐related neurodegenerative diseases. Previous studies suggest that the age effect is more pronounced in the frontal lobe. However, our knowledge of structural complexity changes in male and female brains is still limited. We measured cortical ribbon complexity through fractal dimension (FD) analysis at the hemisphere and lobe level in 7010 individuals from the UK Biobank imaging cohort to study age‐related sex differences (3332 males, age ranged 45–79 years). FD decreases significantly with age and sexual dimorphism exists. With correction for brain size, females showed higher complexity in the left hemisphere and left and right parietal lobes whereas males showed higher complexity in the right temporal and left and right occipital lobes. A nonlinear age effect was observed in the left and right frontal, and right temporal lobes. Differential patterns of age effects were observed in both sexes with relatively more age‐affected regions in males. Significantly higher rightward asymmetries at hemisphere, frontal, parietal, and occipital lobe level and higher leftward asymmetry in temporal lobe were observed. There was no age‐by‐sex‐by asymmetry interaction in any region. When controlling for brain size, the leftward hemispheric, and temporal lobe asymmetry decreased with age. Males had significantly lower asymmetry between hemispheres and higher asymmetry in the parietal and occipital lobes than females. This work provides distinct patterns of age‐related sex and asymmetry differences that can aid in the future development of sex‐specific models of the normal brain to ascribe cognitive functional significance of these patterns in ageing.
Deep multimodal predictome for studying mental disorders
Authors: Rahaman Md Abdur , Chen Jiayu , Fu Zening , Lewis Noah , Iraji Armin , van Erp Theo G. M. , Calhoun Vince D.
Published: September 2022

Characterizing neuropsychiatric disorders is challenging due to heterogeneity in the population. We propose combining structural and functional neuroimaging and genomic data in a multimodal classification framework to leverage their complementary information. Our objectives are two‐fold (i) to improve the classification of disorders and (ii) to introspect the concepts learned to explore underlying neural and biological mechanisms linked to mental disorders. Previous multimodal studies have focused on naïve neural networks, mostly perceptron, to learn modality‐wise features and often assume equal contribution from each modality. Our focus is on the development of neural networks for feature learning and implementing an adaptive control unit for the fusion phase. Our mid fusion with attention model includes a multilayer feed‐forward network, an autoencoder, a bi‐directional long short‐term memory unit with attention as the features extractor, and a linear attention module for controlling modality‐specific influence. The proposed model acquired 92% (p < .0001) accuracy in schizophrenia prediction, outperforming several other state‐of‐the‐art models applied to unimodal or multimodal data. Post hoc feature analyses uncovered critical neural features and genes/biological pathways associated with schizophrenia. The proposed model effectively combines multimodal neuroimaging and genomics data for predicting mental disorders. Interpreting salient features identified by the model may advance our understanding of their underlying etiological mechanisms.
Self‐reported involvement in road traffic crashes in Kenya: A cross‐sectional survey of a nationally representative sample
Authors: Shaikh Masood Ali , Lule Herman , Bärnighausen Till , Lowery Wilson Michael , Abio Anne
Published: September 2022

Background

Road traffic crashes (RTCs) are a global public health burden whose resulting morbidity and mortality disproportionately impact low‐ and middle‐income countries with stressed health systems. There is a paucity of published studies that evaluate the sociodemographic distribution of RTCs using nationally representative samples from the African region.

Aim

To examine population‐wide associations between sociodemographic factors and involvement in RTCs in Kenya.

Methods

Data were obtained from the 2014 Kenyan Demographic Health Survey, representing all 47 counties in Kenya, from May to October of 2014. We estimated the prevalence of RTCs and utilized logistic regression for bivariate and multivariable analyses to determine the sociodemographic factors associated with RTCs. Study variables included age, place of residence, household wealth index, educational attainment, and history of alcohol consumption. We computed odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).

Results

A higher prevalence was reported among men (8.76%) versus women (3.22%). The risk factors among men included being 20−34 years of age, living in a rural area (OR 1.38, 95% CI 1.09, 1.74), drinking alcohol (OR 1.33, 95% CI 1.11, 1.59), and having not higher than a primary (OR 1.90, 95% CI 1.19, 3.03) or secondary (OR 1.68, 95% CI 1.04, 2.71) education. The strongest risk factors for women included the being aged 45−49 (OR 2.30, 95% CI 1.44, 3.67) and 20−24 years (OR 1.81, 95% 1.17, 2.79) as well as being in the fourth wealth quintile (OR 1.83, 95% CI 1.15, 2.91).

Conclusion

Men and the most economically productive age groups were more likely to report being involved in RTCs. Strategies to reduce the occurrences of RTCs should prioritize the most vulnerable sociodemographic groups.
Associations between early‐life and in utero infections and cytomegalovirus‐positive acute lymphoblastic leukemia in children
Authors: Gallant Rachel E. , Arroyo Katti , Metayer Catherine , Kang Alice Y. , de Smith Adam J. , Wiemels Joseph L.
Published: September 2022

Childhood infections and cytomegalovirus (CMV) are associated with pediatric acute lymphoblastic leukemia (ALL). CMV dysregulates the host immune system and alters the immune response to subsequent antigenic exposures. We suspect that this immune dysregulation contributes to increased numbers of symptomatic infections in childhood allowing for expansion of pre‐leukemic clones. We explored the association between childhood infections, maternal infections during pregnancy and CMV‐positive ALL. Using a droplet digital PCR assay, we screened diagnostic ALL bone marrow samples from the California Childhood Leukemia Study (1995‐2015) for the presence of CMV DNA identifying CMV‐positive and CMV‐negative cases. We performed a case‐only analysis (n = 524) comparing the number and types of childhood infections and maternal infections during pregnancy between CMV‐positive and CMV‐negative ALL cases using logistic regression. With increasing numbers of infections in the first 12 months of life, children were more likely to classify to the highest tertile of CMV DNA in the bone marrow at diagnosis (OR: 1.04, 95% CI: 1.01‐1.08). Specifically, those reporting cough or flu in the first 12 months were more likely to be CMV‐positive at ALL diagnosis (OR: 2.15, 95% CI: 1.06‐4.37 and OR: 2.06, 95% CI: 1.17‐3.63 respectively). Furthermore, those with a history of maternal infection during pregnancy were more likely to be CMV‐positive (OR: 2.12, 95% CI: 1.24‐3.62). We hypothesize that children with underlying immune dysregulation develop more symptomatic infections in childhood and ultimately CMV‐positive ALL; this underlying immune dysregulation may be due to early immune system alterations via CMV exposure (in utero or early infancy) proposing a potential link between CMV and ALL etiology.
iTRAQ‐based proteomic analysis of 17β‐Estradiol‐induced anti‐proliferation and apoptosis in mouse thymic epithelial cells by disturbing ribosomal biogenesis
Authors: Liu Yameng , Li Zilong , Guo Dongguang , Ma Yongjiang , Li Yugu
Published: September 2022

Many evidences have suggested that estrogen was associated with thymic atrophy and suppressed thymocyte functions. Thymic epithelial cells (TECs), as a crucial constituent of thymic stroma support a unique microenvironment for thymocyte maturation, but the effects of estrogen on TECs were poorly understood. In our study, we found that 17β‐Estradiol (17β‐E2), one of the primary estrogens, could significantly inhibit cell proliferation, and cause cell cycle arrest in G2/M phase and apoptosis in mouse thymic epithelial cell line 1 (MTEC1 cells) with time‐ and dose‐ dependent. Above all, we provided the systemic and sufficient proteomic profiling of 17β‐E2 (50 nmol/L) acting on MTEC1 cells through isobaric tags for relative and absolute quantitation and LC–MS/MS (Liquid Chromatography Mass Spectrometry/Mass Spectrometry). A total of 71 differentially expressed proteins were identified, of which 61 were up‐regulated and 10 were down‐regulated. Particularly, the differential expression of abundant ribosomal proteins (RPs) was drawing our attention, including RPL3, RPL4, RPS11, RPL17, RPL5, RPS9, RPL13, RPL23A, RPLP2, RPS15A, and RPL29. Most of these proteins have been widely reported exerting extra‐ribosomal function associated with the proliferation and apoptosis of distinct cell types, but not yet observed in TECs. Moreover, bioinformatics analysis revealed that disturbance of ribosomal biogenesis was closely related to the anti‐proliferation and apoptosis in MTEC1 cells upon 17β‐E2. These data highlighted the possible mechanisms of 17β‐E2 on MTEC1 cells through showing adequate differential protein expression profiles. We inferred that 17β‐E2 induced anti‐proliferation and apoptosis in MTEC1 cells in response to alterations of ribosome biogenesis and RPs expression, which will contribute to gaining insight into the internal mechanism of thymic degeneration and exploiting to treat autoimmune diseases in the future.
Mechanical stress‐caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1/forkhead box O1
Authors: Jiang Shilin , Zhang Chengyuan , Lu Ye , Yuan Feng
Published: September 2022

Sirtuin1 (Sirt1)/forkhead box O1 (FoxO1) axis has been reported as a crucial regulator involved in chondral homeostasis of healthy or osteoarthritis (OA) cartilage. In our study, the aim is to investigate whether dioscin functions as an activator of Sirt1/FoxO1 to protect against mechanical stress‐induced chondrocyte dysfunction in vitro and in vivo models. HERB and PubChem databases were implemented to predict dioscin‐related gene targets. Cell and mouse models of OA were established to determine the pharmacological value of dioscin, a steroidal saponin. Cartilage loss in the knee joint was detected by Safranin O staining. Phosphorylation and nucleocytoplasmic shuttling of FoxO1 was observed in mechanical stress‐stimulated chondrocyte and anterior cruciate ligament transection‐induced cartilage injury. However, dioscin treatment repressed FoxO1 phosphorylation and cytoplasmic transfer and elevated Sirt1 protein expression. Dioscin treatment reversed mechanical stress‐induced growth inhibition and apoptosis of chondrocytes and improved cartilage degradation and bone loss in the epiphysis of the distal femur. Moreover, dioscin could maintain the normal phenotype of chondrocytes via mediating multiple gene expressions. Dioscin inhibited apoptosis and metabolic disorders in OA‐like chondrocytes via maintaining the transcriptional activity of FoxO1 and enhancing Sirt1 expression. Dioscin might be a potential Sirt1 activator providing a novel therapeutic schedule for the treatment of OA.
Therapeutic properties and molecular docking study of some phenolic compounds as anti‐human lung cancer potential: A biochemical approach
Authors: Wen Hongqing , Wang Lei , Morsy Kareem , Hamdi Hamida , El‐Kenawy Ayman E. , El‐kott Attalla F.
Published: September 2022

Chloroxine (5,7‐dichloro‐8‐hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate compounds on the 3‐hydroxy‐3‐methylglutaryl coenzyme‐A (HMG‐CoA Reductase) and urease enzymes. We have obtained results for the HMG‐CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result of 5,7‐dichloro‐8‐hydroxyquinoline and Methyl 3,4,5‐trihydroxybenzoate on HMG‐CoA reductase showed lower values 2.28 ± 0.78 and 33.25 ± 5.04 µg/ml, respectively. Additionally, inhibition result of 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate on urease showed lower values 6.18 ± 1.38 and 8.51 ± 1.35 µg/ml, respectively. Molecular docking calculations were made for their biological activities were compared. In the present work, the structures of the related compounds (1 and 2) were drawn using Gaussian 09 software and done geometry optimization at DFT/B3LYP/6‐31G* basis set with aforementioned program. Cytotoxicity potential of these compounds against human lung cancer demonstrated that these compounds had good cytotoxic effects. Both compounds significantly decreased lung cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in lung cell viability. In general, we can say that of the two tested compounds, 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate have cytotoxic effects in all cell types, and this effect is particularly strong in lung cells. Activities were performed at concentrations of 10, 20, 50, 70, and 100 µl and we achieved good results. Lung cell viability (%) value was better at 100 µl concentration and IC50 of them were 54.28 and 48.05 µM.
Maternal–Fetal Drug Development: An Industry Perspective
Authors: Burnham Janelle , Darsey Edress
Published: September 2022

Medicines and vaccines prescribed to pregnant women often have not had pregnant women or lactating women included in clinical trials and products are often not approved by regulatory agencies for use in pregnant women. As a result, practitioners may need to prescribe medicines and give vaccines to this special population with limited drug efficacy and safety information available. Multiple regulatory guidance documents regarding the development of medications for pregnant and lactating women have been developed to encourage drug development and the investigation of medicines and vaccines used in this population. However, clinical, regulatory, ethical, and drug development challenges are encountered when designing clinical trials that include pregnant women and their fetuses, in which innovative methods and trial designs are essential. This article provides an overview of an industry perspective on maternal–fetal drug development that includes a review of the regulatory landscape for developing medicines for pregnant women and their fetuses, trial designs that include pregnant women, identification of gaps and challenges, and strategies for potential maternal–fetal drug development considerations for the future development of medicines and vaccines for pregnant women. Early involvement and discussion of drug and vaccine products with multiple stakeholders, including therapeutic experts, patients, physicians, and regulators, is encouraged to optimize the development of safe and effective medicines and vaccines for pregnant women and their fetuses.
Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI‐FDA Meeting)
Authors: Herzeg Akos , Almeida‐Porada Graça , Charo R. Alta , David Anna L. , Gonzalez‐Velez Juan , Gupta Nalin , Lapteva Larissa , Lianoglou Billie , Peranteau William , Porada Christopher , Sanders Stephan J. , Sparks Teresa N. , Stitelman David H. , Struble Evi , Sumner Charlotte J. , MacKenzie Tippi C.
Published: September 2022

We are living in a golden age of medicine in which the availability of prenatal diagnosis, fetal therapy, and gene therapy/editing make it theoretically possible to repair almost any defect in the genetic code. Furthermore, the ability to diagnose genetic disorders before birth and the presence of established surgical techniques enable these therapies to be delivered safely to the fetus. Prenatal therapies are generally used in the second or early third trimester for severe, life‐threatening disorders for which there is a clear rationale for intervening before birth. While there has been promising work for prenatal gene therapy in preclinical models, the path to a clinical prenatal gene therapy approach is complex. We recently held a conference with the University of California, San Francisco–Stanford Center of Excellence in Regulatory Science and Innovation, researchers, patient advocates, regulatory (members of the Food and Drug Administration), and other stakeholders to review the scientific background and rationale for prenatal somatic cell gene therapy for severe monogenic diseases and initiate a dialogue toward a safe regulatory path for phase 1 clinical trials. This review represents a summary of the considerations and discussions from these conversations.
Engineering graduate students' critical events as catalysts of attrition
Authors: Zerbe Ellen , Sallai Gabriella M. , Shanachilubwa Kanembe , Berdanier Catherine G. P.
Published: September 2022

Background

While attrition from the PhD has been attributed to many high‐level causal factors, such as funding, advisor relationship, and “fit” into a department, few studies have closely examined the mechanisms of attrition or why and how graduate engineering students begin to consider attrition from their doctoral programs.

Design/Method

This study analyzed interviews with current and former doctoral engineering students at research universities across the United States, collected through two closely‐related studies on graduate engineering experiences and attrition consideration. We used critical event analysis as a methodological approach to understand the experiences of a subset of 13 participants, who, at some point in their graduate career, experienced a singular event that caused them to question whether to persist in their PhD program.

Purpose/Hypothesis

The purpose of the present paper is to investigate how graduate engineering students begin to question whether they should remain in their PhD programs of study.

Results

We categorized the environments in which critical events occurred into four quadrants along the lines of University and Nonuniversity Settings and Routine versus Unexpected Contexts, mapping critical events and supporting events to themes from prior literature. The findings demonstrate how seemingly mundane experiences for faculty can be cataclysmic in the eyes of the student; how critical events serve to magnify other issues that had been accumulating over time; and how students may not self‐reflect on their rationale for pursuing a PhD until a critical juncture occurs.

Conclusions

Critical events are one mechanism by which students may begin considering departure from their engineering PhD programs. Some critical events masquerade within mundane contexts, like conversations or conferences (although, in retrospect, students can identify other relevant features contributing to dissatisfaction). From this work, we provide implications geared toward administrators, advisors, and graduate students on how to address and potentially mitigate critical events or their effects, including engaging in conversations about leaving.
Lung Ultrasound in the Evaluation of Neonatal Respiratory Distress Syndrome
Authors: Xin Hua , Wang Lijun , Hao Wei , Hu Haiyang , Li Hecui , Liu Bin
Published: September 2022

Objective

The purpose of this study is to examine the impact of bedside lung ultrasound (LUS) and LUS scores in the evaluating and grading of neonatal respiratory distress syndrome (NRDS).

Methods

We performed a prospective study on 80 children with suspected NRDS. Infants with a PaO2‐to‐FiO2 ratio of <200, 200–300, and >300 mmHg were categorized as the “severe‐NRDS group,” “mild‐NRDS group,” and “non‐NRDS group,” respectively. Left and right lungs were divided into six areas, respectively. For each lung area, a 0‐ to 3‐point score was given.

Results

The most common ultrasonic signs of NRDS include bilateral coalescent B‐lines, thickened pleural line, and white lung without spared areas. Moreover, different LUS scores among non‐NRDS, mild‐NRDS, and severe‐NRDS groups were identified (6.00 ± 4.033, 25.82 ± 3.778 and 27.90 ± 4.071, respectively; P < .05). When the cutoff value of LUS score was selected as 13 for the differentiation of non‐NRDS from NRDS, the sensitivity and specificity were 96.9% and 93.3%, respectively, and the area under the curve (AUC) of receiver operating characteristics (ROC) was 0.938 (95% confidence interval [CI], 0.84–1.00). With a cutoff value of 26.5 for the differentiation between mild‐ and severe‐ARDS, the AUC of ROC curve of the LUS score was 0.707 (95% CI, 0.58–0.83). Similar results were revealed as those with chest X‐ray.

Conclusion

This study showed that LUS and LUS scores complement each other, and are highly reliable and efficient in bedside radiological diagnostic investigations in newborns with NRDS.
Proportion of Malignancy and Evaluation of Sonographic Features of Thyroid Nodules Classified as Highly Suspicious Using ACR TI‐RADS Criteria
Authors: Hussain Najia , Goldstein Michael B. , Zakher Mariam , Katz Douglas S. , Brandler Tamar C. , Islam Shahidul , Rothberger Gary D.
Published: September 2022

Objectives

The reported malignancy rate of highly suspicious thyroid nodules based on the ACR TI‐RADS criteria (TI‐RADS category 5 [TR5]) varies widely. The objective of our study was to determine the rate of malignancy of TR5 nodules at our institution. We also aimed to determine the predictive values of individual sonographic features, as well as the correlation of total points assigned to a nodule and rate of malignancy.

Methods

Our single‐institution retrospective study evaluated 450 TR5 nodules that had cytology results available, in 399 patients over a 1‐year period. Sonographic features and total TI‐RADS points were determined by the interpreting radiologist. Statistical analyses included logistic regression models to find factors associated with increased odds of malignancy, and computing sensitivity, specificity, positive and negative predictive values of various individual sonographic features.

Results

Of the 450 nodules, 95 (21.1%, 95% exact confidence interval 17.4–25.2%) were malignant. Each additional TI‐RADS point increased the odds of malignancy (adjusted odds ratio 1.35, 95% confidence interval 1.13–1.60, P < .001). “Very hypoechoic" was the sonographic feature with the highest specificity and positive predictive value for malignancy (95.5 and 44.8%, respectively), while “punctate echogenic foci” had the lowest positive predictive value (20.0%).

Conclusions

The rate of malignancy of TR5 nodules at our institution was 21.1%, which is lower than other malignancy rates reported in the literature. The total number of points assigned on the basis of the TI‐RADS criteria was positively associated with malignancy, which indicates that TR5 should be viewed as a spectrum of risk.
Giant congenital melanocytic naevus caused by NRAS Q61K mosaicism
Authors: Thielmann Carl M. , Kampmeier Antje , Küchler Alma , Zenker Martin , Wieland Ilse , Matull Johanna , Krefting Frederik , Griewank Klaus , Hadaschik Eva
Published: September 2022

Giant congenital melanocytic naevi (CMN) are large melanocytic lesions commonly associated with neurologic abnormalities. Patients diagnosed with giant melanocytic naevi are at an increased risk of developing melanoma compared to patients with smaller congenital naevi. If patients develop central nervous system (CNS) lesions and exhibit certain characteristic facial features, then the diagnosis of CMN syndrome can be made. We here present the case of a 24‐year‐old female who presented with multiple melanocytic naevi, which had been apparent since birth, and was diagnosed with giant melanocytic naevi caused by NRAS Q61K mosaicism. Both close follow‐up of imaging and clinical study is important so as not to miss cutaneous malignancy and CNS lesions.
Hierarchical Self‐Assembly of Triphilic Main‐Chain‐Type Semifluorinated Alternating Graft Copolymers in Aqueous Solution
Authors: Cheng Jiannan , Yu Qing , Tu Kai , Wang Jinying , Zhang Lifen , Cheng Zhenping
Published: September 2022

Fluorinated copolymers can self‐assemble in solution and form micelles with rare properties due to the peculiar behavior of fluorinated groups. However, the process description of the self‐assembly is still largely phenomenological and difficult to explain due to the tendency of the fluorinated segments to segregate from both the hydrophilic and lipophilic segments, which can result in various morphologies. Herein, the controlled formation of ellipsoidal micelles, disklike micelles, and sheets by hierarchical self‐assembly of triphilic main‐chain‐type semifluorinated alternating graft copolymers (AB)nA‐g‐mOEG is presented (where A represents unit of α,ω‐diiodoperfluoroalkane, B represents the unit of α,ω‐unconjugated diene, and mOEG represents methoxy oligo(ethylene glycol)), which are synthesized by step transfer‐addition and radical‐termination (START) polymerization and azide‐alkyne click chemistry. Furthermore, the possible self‐assembly mechanism of these micron‐level aggregates is proposed, which is ascribed to the hierarchical self‐assembly, crowding effect of hydrophilic chains and the interfacial tension between the fluoroalkane and alkane segments. This study can provide a facile and highly efficient approach to the synthesis of main‐chain‐type fluorinated graft copolymers and expand the research field for the solution self‐assembly of fluorinated copolymers.
Computational benchmarking of putative KIFC1 inhibitors
Authors: Sharma Nivya , Setiawan Dani , Hamelberg Donald , Narayan Rishikesh , Aneja Ritu
Published: September 2022

The centrosome in animal cells is instrumental in spindle pole formation, nucleation, proper alignment of microtubules during cell division, and distribution of chromosomes in each daughter cell. Centrosome amplification involving structural and numerical abnormalities in the centrosome can cause chromosomal instability and dysregulation of the cell cycle, leading to cancer development and metastasis. However, disturbances caused by centrosome amplification can also limit cancer cell survival by activating mitotic checkpoints and promoting mitotic catastrophe. As a smart escape, cancer cells cluster their surplus of centrosomes into pseudo‐bipolar spindles and progress through the cell cycle. This phenomenon, known as centrosome clustering (CC), involves many proteins and has garnered considerable attention as a specific cancer cell‐targeting weapon. The kinesin‐14 motor protein KIFC1 is a minus end‐directed motor protein that is involved in CC. Because KIFC1 is upregulated in various cancers and modulates oncogenic signaling cascades, it has emerged as a potential chemotherapeutic target. Many molecules have been identified as KIFC1 inhibitors because of their centrosome declustering activity in cancer cells. Despite the ever‐increasing literature in this field, there have been few efforts to review the progress. The current review aims to collate and present an in‐depth analysis of known KIFC1 inhibitors and their biological activities. Additionally, we present computational docking data of putative KIFC1 inhibitors with their binding sites and binding affinities. This first‐of‐kind comparative analysis involving experimental biology, chemistry, and computational docking of different KIFC1 inhibitors may help guide decision‐making in the selection and design of potent inhibitors.
The Cauchy problem for Laplace's equation via a modified conjugate gradient method and energy space approaches
Authors: Amdouni Saber , Ben Abda Amel
Published: September 2022

In the present work, we focus on the resolution of the Cauchy Laplace problem using an energetic variational minimization approach in the framework of a finite element method. A new strategy of regularization, called a filtering procedure regularization, is developed. The advantage of using this new regularization is that it does not require a regularization parameter and is easy to implement. An optimal a priori error estimate is proven, for the first time up to our knowledge, in the context of the finite element method. Some numerical results are presented to illustrate the performance of our approach.
Impact of Physiologically Relevant Genistein Exposure at Different Time Windows on Puberty Onset and Neuroendocrine Function in Female Rats
Authors: Xiong Jingyuan , Tian Ye , Ma Guochen , Wang Xiaoyu , Shan Shufang , Cheng Guo
Published: September 2022

Scope

Puberty timing, critical for adulthood wellbeing, is influenced by the environment, life‐style, and diets. However, differential puberty‐interfering effects of soy and soy isoflavone are observed in both epidemiological and toxicological studies. Additionally, their impact on neuroendocrine function at various pre‐pubertal developmental windows is unclear.

Methods and results

This study investigates the effect of genistein, a typical soy isoflavone, at neonatal, lactational, and post‐weaning stages on the time of vaginal opening and determines the levels of neuroendocrine factors in female rats using immunofluorescence, immunochemistry, and enzyme‐linked immunosorbent assays. A physiologically relevant dosage (10 mg kg−1) is used to resemble human exposure. The results show that genistein exposure at lactational stage significantly accelerates vaginal opening time, marginally increases hypothalamic gonadotropin‐releasing hormone (GnRH) secretion, significantly enhances kisspeptin receptor expression, and markedly elevates blood levels of GnRH, luteinizing hormone, and follicle‐stimulating hormone, while neonatal and post‐weaning exposures do not induce significant alternations.

Conclusion

Lactational stage may be an important window for genistein to impact reproductive development and neuroendocrine regulations.
A broadband intermodulation reference generator based on artificial nonlinear dipole
Authors: Zhang Keyue , Chen Xiong , Zhao Xiaolong , Cao Zhi , He Yongning
Published: September 2022

Accurate passive intermodulation (IM) test calls for precise IM reference for verifying and evaluating the test error from the tester, which makes the IM calibrator source with a wide working band and dynamic range important. This letter reports on a low‐cost and broadband IM generator with a compact area of 5 × 5 cm2. The broadband IM source is designed and demonstrated on the coplanar waveguide structure, where an artificial nonlinear dipole is used to generate IM reference. In special, the dipole is constructed by a diode (HSMS 2822) and two independent copper islands with optimized size. By controlling the bias voltage across the diode, the IM magnitude level can be changed accordingly. The IM tunable dynamic range is over 47.5 dB that covers GSM 800 MHz, GSM 900 MHz, DCS 1800 MHz, and TD‐LTE band. Meanwhile, the obtained IM has an improved IM‐bias flat response.
High‐fidelity, high‐spatial‐resolution diffusion magnetic resonance imaging of ex vivo whole human brain at ultra‐high gradient strength with structured low‐rank echo‐planar imaging ghost correction
Authors: Ramos‐Llordén Gabriel , Lobos Rodrigo A. , Kim Tae Hyung , Tian Qiyuan , Witzel Thomas , Lee Hong‐Hsi , Scholz Alina , Keil Boris , Yendiki Anastasia , Bilgiç Berkin , Haldar Justin P. , Huang Susie Y.
Published: September 2022

Diffusion magnetic resonance imaging (dMRI) of whole ex vivo human brain specimens enables three‐dimensional (3D) mapping of structural connectivity at the mesoscopic scale, providing detailed evaluation of fiber architecture and tissue microstructure at a spatial resolution that is difficult to access in vivo. To account for the short T2 and low diffusivity of fixed tissue, ex vivo dMRI is often acquired using strong diffusion‐sensitizing gradients and multishot/segmented 3D echo‐planar imaging (EPI) sequences to achieve high spatial resolution. However, the combination of strong diffusion‐sensitizing gradients and multishot/segmented EPI readout can result in pronounced ghosting artifacts incurred by nonlinear spatiotemporal variations in the magnetic field produced by eddy currents. Such ghosting artifacts cannot be corrected with conventional correction solutions and pose a significant roadblock to leveraging human MRI scanners with ultrahigh gradients for ex vivo whole‐brain dMRI. Here, we show that ghosting‐correction approaches that correct for either polarity‐related ghosting or shot‐to‐shot variations in a separate manner are suboptimal for 3D multishot diffusion‐weighted EPI experiments in fixed human brain specimens using strong diffusion‐sensitizing gradients on the 3‐T Connectom MRI scanner, resulting in orientationally biased dMRI estimates. We apply a recently developed advanced k‐space reconstruction method based on structured low‐rank matrix (SLM) modeling that handles both polarity‐related ghosting and shot‐to‐shot variation simultaneously, to mitigate artifacts in high‐angular resolution multishot dMRI data acquired in several fixed human brain specimens at 0.7–0.8‐mm isotropic spatial resolution using b‐values up to 10,000 s/mm2 and gradient strengths up to 280 mT/m. We demonstrate the improved mapping of diffusion tensor imaging and fiber orientation distribution functions in key neuroanatomical areas distributed across the whole brain using SLM‐based EPI ghost correction compared with alternative techniques.
Distribution law of strain energy density for stiffness design of GFRP, UT/GFRP, and VRB/GFRP hybrid hat‐shaped beams
Authors: Zhang Yu , Duan Libin , Liu Xing , Zheng Haiyang , Du Zhanpeng , Xu Wei , Wu Chuang
Published: September 2022

The structural optimization for stiffness performances with hundreds or thousands of design parameters is a complex and time‐consuming process. This is because, on the one hand, the direct relationship between the stiffness and the many design parameters is unknown, and on the other hand, the sensitivity of a single design parameter to the global stiffness is hardly obtained. Therefore, transforming the global stiffness performance to the strain energy density (SED) distribution over the whole structure can significantly simplify the optimization problem. In this work, the relationships among the design parameters, SED distribution and stiffnesses of glass fiber reinforced plastic (GFRP), uniform thickness metal (UT)/GFRP, and variable‐thickness rolled blanks (VRB)/GFRP hat‐shaped beams are investigated through numerical simulations. It is found that the higher SED of the all hat‐shaped beam structure indicates a worse stiffness performance under both bending and torsional conditions. When the SED of the GFRP hat‐shaped beam increases 6.65%, its bending stiffness decreases 10.8%. It is also found that the smaller SED distribution variance of the all hat‐shaped beam structures indicates a better stiffness performance. When the SED distribution variances of the VRB and GFRP in the VRB/GFRP hybrid beam are, respectively, reduced by 70.78% and 85.56%, the bending stiffness of the hybrid beam is increased by 50.83%. The above relations and conclusions indicate that the structural stiffness optimization problem with many design parameters can be replaced with the structural SED distribution variance minimization problem, which would not need the unavailable sensitivities of the design parameters to the global stiffness. Besides, compared to the GFRP hat‐shaped beam, with the same mass, volume or cost, the bending stiffnesses of the VRB/GFRP hat‐shaped beam, respectively, increases by 196.1%, 476.5%, and 676.4%, and its torsional stiffnesses, respectively, increases by 70.9%, 233.0%, and 348.4%. This means the combination of VRB and GFRP in the beam structure can reach a better stiffness performance and a higher lightweight level.