bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of different pickling methods on physicochemical properties and flavor profiles of Tongling white ginger: Dry‐salting, brine‐pickling, and inoculation‐pickling
Authors: Zong Kaili , Jin Feixiang , Wang Daquan , Hu Hongchao , Cui Haipeng , Yang Jianting
Published: January 2024

Tongling white ginger is a Chinese fermented vegetable with unique flavors. However, little is known about its physicochemical properties, flavor characteristics, and sensory evaluation. The study examined the physicochemical (pH, titratable acidity [TA], nitrite, soluble protein, and color) and flavor characteristics (organic acids, free amino acids, and volatiles) of white ginger during fermentation. The results showed that the pH value and soluble protein in the dry‐salted, brine‐pickled, and inoculation‐pickled decreased significantly while the TA value increased significantly, inoculation‐pickled can effectively reduce the content of nitrite. After fermentation, inoculation‐pickled produced the highest content of organic acids, while dry‐salted produced the highest total amount of free amino acids. A total of 70, 68, 70, and 69 volatile compounds were identified in fresh, dry‐salted, brine‐pickled, and inoculation‐pickled white ginger. The total contents of terpenoids of Tongling white ginger by three fermentation methods decreased; the total contents of alcohols and aldehydes were the highest in brine‐pickled, and esters and ketones were more abundant in inoculation‐pickled. The results showed that inoculation‐pickled could shorten the fermentation time of Tongling white ginger, produce a unique flavor, and have the highest sensory score.
Evaluation of fig‐milk dessert bioactive properties as a potential functional food
Authors: Zare Niloofar , Sedighi Mahsa , Jalili Hasan , Zare Hamid , Maftoon Azad Neda
Published: January 2024

The fig‐milk dessert, a traditional and nutritionally rich treat infused with bioactive compounds, was subjected to a comprehensive analysis in this study. The novelty of this research lies in the investigation of the in vitro antioxidant, anticancer, and antimicrobial potential of the fig‐milk dessert. This was accomplished through the utilization of the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay, Annexin/propidium iodide staining, microtiter plate‐based assay and agar well diffusion, respectively, for the first time. Additionally, the study assessed the total phenols and flavonoid content of the extract using the Folin–Ciocalteu assay and the aluminum chloride method, respectively. The findings revealed that the cooking method exerted a significant influence on the bioactive properties and nutritional composition of the dessert. Among the samples analyzed, CM1, consisting of figs steamed for 2 min and milk heated to 70°C, exhibited remarkable characteristics. This sample demonstrated the highest peptide concentration (1290 mg/L), superior antioxidant and anticancer activities, and favorable sensory attributes. Specifically, CM1 induced apoptosis in 84% of AGS cells and inhibited 68% of free radicals in the DPPH assay. It is noteworthy that the fig‐milk dessert did not exhibit any antibacterial properties. These discerning results carry substantial implications for the development of functional dairy products endowed with both nutritional and potential therapeutic properties.
Correlation of TIRADS scoring in thyroid nodules with preoperative fine needle aspiration biopsy and postoperative specimen pathology
Authors: Atar Cihan , Dalcı Kubilay , Aktar Yasemin , Totik Nazlı , Topal Uğur , Eray İsmail Cem , Akçam Atılgan Tolga , Sakman Gürhan
Published: January 2024

Introduction

The aim of our study is to determine the value of Thyroid Imaging Reporting and Data Systems (TIRADS) scoring in predicting malignancy in thyroid nodules by examining its relationship with fine needle aspiration biopsy and postoperative histopathological results.

Materials and Methods

In this study, patients who underwent surgery after ultrasonographic examination and fine needle aspiration biopsy for thyroid nodules at the General Surgery Clinic of Çukurova University Faculty of Medicine between January 2014 and November 2021 were retrospectively analyzed. The thyroid ultrasonography and fine needle aspiration biopsy of the included patients were performed by a clinician with 15 years of experience. The ultrasonographic features of the nodules were re‐evaluated by the same clinician, and the American College of Radiology (ACR) TIRADS score was determined. Fine needle aspiration biopsy results were grouped according to Bethesda criteria. Postoperative histopathological examination results were divided into two groups: benign and malignant. The ACR TIRADS score was compared with fine needle aspiration biopsy and histopathological results. The performance of the ACR TIRADS score in predicting malignancy was determined.

Results

79.8% of the 397 patients were female, and the mean age was 50.9 ± 12.8 years. The mean diameter of the nodules was 27.4 ± 15.8 mm. There was a significant, positive, but weak correlation between ACR TIRADS and Bethesda (p < 0.001) (r = 0.33). When the ACR TIRADS score was compared with histopathological results, it was found that the rate of malignancy increased as the TIRADS score increased (p < 0.001). The rates of malignancy diagnosis were 0% for TR1, 13.2% for TR2, 21.7% for TR3, 50.3% for TR4, and 72.4% for TR5. The area under the receiver operating characteristic curve for TIRADS in predicting malignancy was 0.747 (95% CI: 0.699–0.796, p < 0.001). TIRADS can distinguish malignancy with 75% accuracy. The optimal cutoff point was determined as TR4 with 80.3% sensitivity and 60.8% specificity.

Conclusion

The ACR TIRADS scoring system is an effective risk classification system for thyroid nodules, providing 75% accuracy in predicting malignancy, with 80.3% sensitivity and 60.8% specificity values.
ALCAM is a biomarker of tumor aggressiveness and worse prognosis in glottic laryngeal squamous cell carcinoma
Authors: Nicolau‐Neto Pedro , Peryassú Bernardo Cacciari , de Carvalho Flávia Nascimento , Souza‐Santos Paulo Thiago , Valverde Priscila , Nascimento Cristina Moreira , Costa Izabella , Dias Fernando L. , Pinto Luis Felipe Ribeiro
Published: January 2024

Background

Laryngeal squamous cell carcinoma (LSCC) is the second most frequent head and neck tumor. Prognosis of patients with LSCC has not improved in recent decades, showing a need for the identification of prognostic biomarkers and new therapeutic targets. Recently, we showed that ALCAM overexpression was associated with glottic LSCC prognosis.

Objectives and methods

Aiming to validate the prognostic value of ALCAM, we evaluate the ALCAM protein levels by immunohistochemistry in 263 glottic LSCC surgically treated with neck dissection.

Results

ALCAM was expressed in 48.7% and overexpressed in 36.5% of glottic LSCC samples. ALCAM overexpression was associated with lymph node metastasis (p = 0.030), lymphovascular involvement (p = 0.0002), high‐grade tumors (p = 0.025), and tumor relapse (p = 0.043). Multivariate survival analyses showed an overfitting between ALCAM overexpression and lymph node metastasis as a prognostic variable.

Conclusions

High ALCAM expression was associated with an aggressive glottic LSCC profile.
Streamflow change of major rivers over the Tibetan Plateau during the last half century and its possible causes
Authors: Yong Bin , Qi Weiqing , Lu Dekai , Lyu Yi , Liao Aiming , Wang Guoqing , Ren Liliang , Zhang Jianyun
Published: January 2024

The streamflow on the Tibetan Plateau (TP) plays an important role in the water supply of Asia's main river basins. To enhance understanding of hydrologic cycle under the pronounced warming over the TP, this study comprehensively investigates the streamflow changes at the upstream of six major rivers (Yellow River, Yalong River, Jinsha River, Lancang River, Nu River, and Yarlung Zangbo River) originating from the TP, and then diagnoses their possible causes by analysing the impacts of climate variability and human activities. Results indicate that these six major rivers studied have generally insignificant increasing trends in annual streamflow during the last half century, except for two stations. The significant increase appears at the Tuotuohe station in the headwater area of Jinsha River, while the dramatic decrease occurs at the Yunjinghong station in the downstream of Lancang River. In terms of climate factors, the six river basins show a distinct warming trend, along with a noticeable increase in precipitation over the central and northern regions. Pan evaporation, wind speed, sunshine duration, and relative humidity have been found to gradually decrease in most areas. As for the Tuotuohe station, both warming‐induced meltwater and increasing precipitation might jointly contribute to the increasing streamflow. But for the Yunjinghong station, the results simulated by the Variable Infiltration Capacity (VIC) model indicate that human activities, especially for the impoundment processes of Xiaowan and Nuozhadu dams, significantly influenced the streamflow, contributing to approximately 69% of the streamflow reduction during 2009–2013. In the context of accelerated global warming, greater attention should be paid to hydrometeorological changes on the TP to offer further insights for the water resources management of the ‘Asian Water Tower’.
Stable isotopic compositions and controlling factors of precipitation and atmospheric vapour in the headwaters of the Shule River
Authors: Zhang Zihan , Zhao Liangju , Wang Ninglian , Liu Hang , Xie Cong , Dong Xiying , Li Xingru
Published: January 2024

Stable isotopic compositions of precipitation (δ18Op, δ2Hp and d‐excessp) and atmospheric vapour (δ18Ov, δ2Hv and d‐excessv) with high spatial–temporal resolution are crucial in revealing hydrologic cycle. Based on the variation characteristics of δ18Op/δ18Ov, δ2Hp/δ2Hv and d‐excessp/d‐excessv in the headwaters of the Shule River (HSR) on hourly and daily scales from June to September 2018, this study analysed the relationships between δ18Op/δ2Hp and δ18Ov/δ2Hv combined with the equilibrium fractionation model, as well as δ18Op/δ18Ov and meteorological factors. The slopes of local meteoric water line (LMWL) and the δ2Hv‐δ18Ov fitting equation were similar (7.96 and 7.94) with both intercepts exceeding 10, reflecting the great contribution of recycling moisture. The values of δ18Ov/δ2Hv were lower than δ18Op/δ2Hp but with consistent variation patterns throughout the period. The equilibrium simulation results suggested that precipitation and atmospheric vapour almost approached isotopic equilibrium state, especially during monsoon intrusion period. Affected by monsoon intrusion, the slopes and intercepts of the LMWLs and the δ2Hv‐δ18Ov fitting equations were smaller than those during non‐monsoon period and d‐excess and δ18O were negatively correlated. Relative humidity had significant negative correlations with δ18Op and δ18Ov in the whole period, however, the positive correlations between δ18Op/δ18Ov and temperature were observed during non‐monsoon and monsoon intrusion period, respectively. Our results demonstrated that precipitation and atmospheric vapour isotopic compositions exhibited consistency under the influence of diverse moisture sources, while more complex relationships were found between δ18Op/δ18Ov and meteorological factors. This research provided evidence for using the isotopic compositions of atmospheric vapour to indicate moisture sources, and can improve understanding of the water cycle and eco‐hydrological process from the perspective of the interaction between water and gas phases of the inland river basin in northwest China.
Ocean air masses from the East Asian monsoon dominate the land‐surface atmospheric water cycles in the coastal areas of Liaodong Bay, Northeast China
Authors: Du Yi‐Yuan , Wen Ri‐Hong , Jia Qing‐Yu , Liu Lu‐Lu , Hu Yue‐Hua , Li Jia‐Yuan , Pan Jie , Yuan Xia , Peng Jiang , Zakari Sissou , Panthee Shristee , Song Liang , Liu Wen‐Jie , Yang Bin
Published: January 2024

Long‐term atmospheric water vapour hydrogen (δ2H), oxygen (δ18O) and deuterium excess (d‐excess) can provide unique insights into the land‐atmosphere coupling processes. The in‐situ measurements of atmospheric water vapour δ2H, δ18O and d‐excess were conducted above a reed wetland of Liaodong Bay (2019–2020). We found significant inter‐annual variations in atmospheric water vapour isotopes between the two growing (May–September) seasons. The δ2H, δ18O and d‐excess of atmospheric water vapour exhibited different seasonal and diurnal cycles concerning the vertical measurement heights, especially in 2019. The isotopic differences of atmospheric water vapour among vertical measurement heights were more evident in the daytime. Rainfall events directly impacted the diurnal patterns of water vapour isotopes, and the influences depended on rainfall intensities. However, only weak correlations existed between water vapour isotopes and local meteorological factors (R2 = 0.01–0.16, p < 0.001), such as water vapour concentration (w), Relative Humidity (RH) and surface air temperature (Ta). Based on the back‐air trajectory analyses, the spatial–temporal dynamics of atmospheric water vapour isotopes are highly synchronized with monsoon activities. Different water vapour sources influence the water vapour isotope in this region and the higher d‐excess value is related to the intense convection brought by the monsoon. High‐resolution measurements of atmospheric water vapour isotopes will improve our understanding of the hydrological cycles in coastal areas.
Runoff response to multiple land‐use changes and climate perturbations
Authors: Yang Mingjie , Xue Lianqing , Liu Yuanhong , Wang Wenzhuang , Han Qiang , Liu Saihua , Fu Ruizhe
Published: January 2024

Runoff response to multiple land‐use changes and climate perturbations is distinct, and the main influencing factors vary significantly in different regions. However, few have simultaneously considered the effects of multiple land use changes (vegetation cover changes, terraces and check‐dams construction, and urban expansion) and climatic perturbations (precipitation, potential evapotranspiration, and temperature) on runoff and constructed separate expressions for distinct study areas. This article attempted to determine the main influencing factors of runoff according to the fitting function in the eight subregions of the middle Yellow River (MYR), construct the expressions between the controlling parameter in the Budyko framework and the main factors, and quantify the contribution of climate factors and land use changes to runoff by combining the elasticity coefficient in each subregion. The results indicated that climate factors and land use changes could significantly impact controlling parameters, and there were differences between regions. Climate change promoted an increase in runoff, while land use change promoted its reduction, and the reduction value outweighed its increase. In terms of land use changes, increasing vegetation coverage could suppress runoff reduction, while constructing terraces and check‐dams could promote its reduction. The urban expansion benefited runoff collection and, therefore, could suppress runoff reduction. Its absolute contribution rate exceeded 200% in apparent urban expansion areas. In addition, the contribution rates of land use to runoff changes in the northern arid and semi‐arid regions were significantly higher than those in the southern, and they were more sensitive to land use changes. The research results can provide a reference for analysing the runoff response to different land‐use changes and can further advance people's understanding of the water cycle.
Augmented drug resistance of osteosarcoma cells within decalcified bone matrix scaffold: The role of glutamine metabolism
Authors: Ren Jiaxin , Zhao Cheng , Sun Ruizhu , Sun Jian , Lu Laiya , Wu Jun , Li Shuaijun , Cui Lei
Published: January 2024

Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three‐dimensional model of osteosarcoma constructed by seeding tumor cells (MG‐63 and MNNG/HOS Cl no. 5) within demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG‐63 and MNNG/HOS Cl no. 5 cell lines as compared to two‐dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted in a decrease in drug resistance of osteosarcoma, which could be restored by α‐ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance.
Tuning the Sign and Magnitude of Complexation‐Induced pKa Shifts in Cucurbit[7]uril Host‐Guest Complexes by Molecular Engineering
Authors: Trevisan Alberto , Ferreira Ana S. D. , Marrec Philippe , Parola A. Jorge , Basílio Nuno
Published: January 2024

Cucurbiturils are popular macrocyclic receptors that bind complementary guest molecules with high affinity in aqueous environments. They are recognized for their ability to selectively bind positively charged guest molecules, including ionizable ammonium cations which frequently display much higher affinity than their neutral counterparts. This selectivity for the protonated species is translated into an increase in the basicity of encapsulated guests (i. e. into complexation‐induced positive pKa shifts). However, despite being very rare, negative pKa shifts can be observed for specific guests. Following a previous work from our group reporting slightly negative pKa shifts for flavylium and chalcone dyes featuring N‐diethylamino substituents (ΔpKa=− 0.2), herein we report a systematic study on the complexation of N‐dialkylaminochalcones with CB7. The results show that the pKa shifts of these host‐guest complexes can be rationally tuned by the nature of the N‐dialkylamino groups and as well by target substitutions on the skeleton of the dye, allowing the design of a CB7 1 : 1 host‐guest complex with a ΔpKa=− 0.6.
Does institutional quality matter for renewable energy promotion in OECD economies?
Authors: Rafiq Shuddhasattwa , Paramati Sudharshan Reddy , Alam Md. Samsul , Hafeez Khalid , Shafiullah Muhammad
Published: January 2024

This study examines the effect of institutional quality on renewable energy promotion in OECD economies. The study employs annual data from 1980 to 2014 on 18 OECD economies. The robust panel unit root tests show that all the considered variables have a similar order of integration, indicating that they are nonstationary at their levels but stationary at the first‐order differences. The panel cointegration test with structural breaks and cross‐section dependence confirms a long‐run equilibrium association between institutional quality, renewable energy consumption and control variables. The analysis of long‐run estimations displays that better institutional quality makes a unique and substantial contribution to promoting renewable energy consumption. Overall, the study findings offer important policy implications highlighting the importance of institutional quality for the growth of renewable energy and a sustainable world.
Social support buffers the impact of pregnancy stress on perceptions of parent–infant closeness during the COVID‐19 pandemic
Authors: Becker Emma , Atkinson Leslie , Gonzalez Andrea , Khoury Jennifer
Published: January 2024

Pregnant individuals and parents have experienced elevated mental health problems and stress during COVID‐19. Stress during pregnancy can be harmful to the fetus and detrimental to the parent–child relationship. However, social support is known to act as a protective factor, buffering against the adverse effects of stress. The present study examined whether (1) prenatal stress during COVID‐19 was associated with parent–infant closeness at 6 months postpartum, and (2) social support moderated the effect of prenatal stress on the parent–infant relationship. In total, 181 participants completed questionnaires during pregnancy and at 6 months postpartum. A hierarchical linear regression analysis was conducted to assess whether social support moderated the effect of stress during pregnancy on parent–infant closeness at 6 months postpartum. Results indicated a significant interaction between prenatal stress and social support on parents’ perceptions of closeness with their infants at 6 months postpartum (β = .805, p = .029); parents who experienced high prenatal stress with high social support reported greater parent–infant closeness, compared to those who reported high levels of stress and low social support. Findings underscore the importance of social support in protecting the parent–infant relationship, particularly in times of high stress, such as during the COVID‐19 pandemic.
Leveling the field: Development of an asynchronous interactive module series for genetic counseling trainees on molecular testing and variant interpretation
Authors: Reichert Sara L. , Dechene Elizabeth , Lulis Lauren , Valverde Kathleen , Conway Laura , Dulik Matthew
Published: January 2024

The need for education focusing on genomic technologies and variant interpretation for genetic counseling trainees has prompted genetic counseling training programs to alter their curricula to incorporate this content. Given students' diverse experiences prior to matriculation into genetic counseling training programs, students' familiarity with these topics may vary. Following receipt of feedback from trainees at a large genetic counseling program regarding an existing course focused on molecular technologies, a three‐part asynchronous module series was created as a prerequisite to this course as an opportunity to align knowledge. Designed to be completed by students on their own time and at their own pace, the modules allowed for additional instruction without increases in classroom time or credit hours. Content included a refresh on genetics concepts and an introduction to available genetics resources for developing a differential diagnosis as well as variant interpretation framework. Modules utilized a clinical scenario to anchor learning with interactive content, allowing students to progress at their own pace and explore content as they found necessary. Completion of this asynchronous module series was required by incoming first‐year students prior to the start of the academic semester. Following completion, students were asked to provide feedback on the module series. Reviews were primarily positive with students indicating that while the content was not entirely new, they found the review valuable and would be likely to reference the modules later in their genetic counseling training. Areas identified for improvement included additional detail regarding genetic testing methods as well as adjusting the interactive content to ensure accessibility for all students and systems. Taken together, the development and implementation of this asynchronous series as an additional component to genetic counseling training was considered a success and this approach can be considered to address additional topics dependent on a programs' needs.
Development of a flipped learning course to deliver and scale molecular variant evaluation education: A quality improvement initiative
Authors: Balcom Jessica R. , Ellingson Marissa S. , Bowler Carrie A. , Richardson Darcy M. , Kruisselbrink Teresa , Thomas Brittany C.
Published: January 2024

Over the past several decades, molecular genetic testing volumes have grown and testing has expanded from single‐gene assays to multigene panels, exome sequencing, and genome sequencing. The number of molecular genetic variants that require manual interpretation has grown simultaneously, resulting in an increased demand for education on molecular variant evaluation (MVE). To meet this growing need, a team of genetic counselors and educational experts undertook a quality improvement (QI) initiative with the objectives of assessing, standardizing, and scaling access to MVE education, without increasing instructor time to deliver the education. Using the Six Sigma define–measure–analyze–improve–control (DMAIC) framework, a flipped learning course with a series of standardized online modules was developed to deliver MVE education in an enduring and accessible format for a diverse group of learners. Outcome measures included the number of online modules developed, the number of individual learners and unique learner groups accessing MVE education, and direct instruction time required to deliver MVE education. Countermeasures to ensure maintenance of educational quality included post‐course learner satisfaction scores and performance on competency assessments. Both the total number of learners and the number of unique learner groups accessing MVE education increased, while instructor time required to deliver content per learner decreased. Learner satisfaction scores remained constant and performance on competency assessments improved. The QI initiative successfully scaled MVE education to a diverse group of learners without decreasing learner outcomes or satisfaction. The flipped learning format provides a scalable and flexible educational model for instructors and learners in a rapidly changing environment that often includes remote work and education.
Prognosis and therapy in thyroid cancer by gene signatures related to natural killer cells
Authors: Jin Zhen , Han Yadong , Zhang Jiaxin , Liu Zhao , Li Ran , Liu Zhao
Published: January 2024

Background

Natural killer (NK) cells are crucial to cancer development and prognosis. However, the role of NK cell‐related genes in immunotherapy and the tumor immune microenvironment (TIME) is not well understood. This study aimed to develop reliable risk signatures associated with NK cell‐related genes for predicting thyroid cancer (THCA).

Methods

The single‐cell RNA sequencing (scRNA‐seq) data from seven THCA samples (GSE184362) and bulk‐RNA‐seq data of 502 THCA patients (TCGA‐THCA) were included. The scRNA‐seq data was analyzed using the “Seurat” R package to identify differentially expressed genes in NK cells. The clustering analysis was carried out using the R package “ConsensusClusterPlus”. The gene set variation analysis (GSVA) algorithm was applied to assess the variations in biological pathways among subtypes. The ESTIMATE algorithm was utilized to calculate the scores for stromal, immune and estimate variables. In addition, we used the single sample Gene Set Enrichment Analysis and CIBERSORT algorithms to assess the degree to which immune cells and pathways related to immunity were enriched based on the meta‐cohort. In the TCGA‐THCA cohort, the “glmnet” R package was used for the gene selection, and LASSO Cox analysis was used to construct prognostic features. The “maftools” R package was used to examine the somatic mutation landscape of THCA in both low‐ and high‐risk groups.

Results

One‐hundred and eighty‐five NK cell marker genes were screened, and nine genes were associated with the THCA prognosis. KLF2, OSTF1 and TAPBP were finally identified and constructed a risk signature with significant prognostic value. KLF2 and OSTF1 were protective genes, and TAPBP was a risk gene. Patients at high risk had a considerably lower overall survival compared with those at low risk. Mutations in the TCGA‐THCA cohort were predominantly C > T. Increased tumor mutation burden (TMB) levels were linked to overall survival. The low‐risk H‐TMB+ group had a better prognosis, while the high‐risk L‐TMB+ group had the worst prognosis.

Conclusion

Natural killer cell‐related genes KLF2, OSTF1 and TAPBP were used to develop a novel prognostic risk signature, offering a new perspective on the prognosis and treatment of THCA.
A case of benign immunoglobulin D monoclonal gammopathy of undetermined significance with 26 years of follow‐up
Authors: Anderson Larry D. , Bladé Joan , Kyle Robert A.
Published: January 2024

The presence of a serum immunoglobulin D (IgD) monoclonal protein (M‐protein) is seen in < 1% of patients with monoclonal gammopathies and is usually indicative of a malignant plasma cell disorder. Only a few cases of well‐documented benign monoclonal gammopathy of undetermined significance (MGUS) of IgD subtype have been reported, and only 2 of those had over 5 years of follow‐up at the time they were reported. Herein we describe longer‐term follow‐up of one of those 2 patients who has subsequently passed away from unrelated causes but never developed multiple myeloma or amyloidosis after 26 years of follow‐up. Although IgD MGUS is extremely rare, this case confirms that presence of an IgD M‐Protein is not always synonymous with a malignant plasma cell process.
Tetrahydrobiopterin (BH4) treatment stabilizes tyrosine hydroxylase: Rescue of tyrosine hydroxylase deficiency phenotypes in human neurons and in a knock‐in mouse model
Authors: Jung‐KC Kunwar , Tristán‐Noguero Alba , Altankhuyag Altanchimeg , Piñol Belenguer David , Prestegård Karina S. , Fernandez‐Carasa Irene , Colini Baldeschi Arianna , Sigatulina Bondarenko Maria , García‐Cazorla Angeles , Consiglio Antonella , Martinez Aurora
Published: January 2024

Proteostatic regulation of tyrosine hydroxylase (TH), the rate‐limiting enzyme in dopamine biosynthesis, is crucial for maintaining proper brain neurotransmitter homeostasis. Variants of the TH gene are associated with tyrosine hydroxylase deficiency (THD), a rare disorder with a wide phenotypic spectrum and variable response to treatment, which affects protein stability and may lead to accelerated degradation, loss of TH function and catecholamine deficiency. In this study, we investigated the effects of the TH cofactor tetrahydrobiopterin (BH4) on the stability of TH in isolated protein and in DAn‐ differentiated from iPSCs from a human healthy subject, as well as from THD patients with the R233H variant in homozygosity (THDA) and R328W and T399M variants in heterozygosity (THDB). We report an increase in TH and dopamine levels, and an increase in the number of TH+ cells in control and THDA cells. To translate this in vitro effect, we treated with BH4 a knock‐in THD mouse model with Th variant corresponding to R233H in patients. Importantly, treatment with BH4 significantly improved motor function in these mice, as demonstrated by increased latency on the rotarod test and improved horizontal activity (catalepsy). In conclusion, our study demonstrates the stabilizing effects of BH4 on TH protein levels and function in THD neurons and mice, rescuing disease phenotypes and improving motor outcomes. These findings highlight the therapeutic potential of BH4 as a treatment option for THDA patients with specific variants and provide insights into the modulation of TH stability and its implications for THD management.
Coexisting Th1 and Th2 cytokines in patients with collagenous gastritis and implications for its pathogenesis
Authors: Liu Qingqing , Wang Yanping , Harpaz Noam
Published: January 2024

Objectives

Collagenous gastritis (CG) is a rare cause of refractory dyspepsia and anemia that frequently affects children and young adults and whose histological hallmark is chronic mucosal inflammation with a subepithelial collagen band. The etiology remains obscure, and no established treatments exist. We investigated the pathogenesis of CG by determining the expression profiles of genes related to immunity and inflammation in index biopsies.

Methods

Gastric biopsies from 10 newly diagnosed patients with CG were evaluated using the NanoString nCounter assay. Gastric biopsies from 14 normal individuals served as controls. The gene expression ratios for CG versus controls were determined in pooled samples and confirmed in individual samples by quantitative reverse transcription polymerase chain reaction. The results were compared with previously reported expression data from a cohort of patients with collagenous colitis, a colonic disorder with similar morphology, including subepithelial collagen band.

Results

CG biopsies featured enhanced expression of key genes encoding both Th1 (IFNγ, TNF‐α, IL‐2, IL‐10, IL‐12A, IL‐12B, and IL‐18) and Th2 cytokines (IL‐3, IL‐4, IL‐5, IL‐6, and IL‐13). In contrast, biopsies from patients with CC exhibited upregulated Th1 cytokines only.

Conclusions

We show in this first published gene expression profiling study that CG involves simultaneous upregulation of Th1 and Th2 cytokines. This finding is unique, contrasting with other types of chronic gastritis as well as with collagenous colitis, which shares the presence of a collagen band. Involvement of Th2 immunity in CG would support further investigation of potential dietary, environmental, or allergic factors to guide future therapeutic trials.
Mass‐correlated rotational Raman spectra and the structure of furan
Authors: Rukiye Özer Begüm , Chan Lee Jong , Heo In , Schultz Thomas
Published: January 2024

We present mass‐correlated rotational alignment spectroscopy and the first high‐resolution rotational Raman spectra for furan. Spectra were measured with a spectral range up to 0.5 THz and a resolution down to 1.6 MHz. Spectra for 13C and 18O isotopologues were observed in their corresponding mass channels at natural abundance. Based on our data and literature constants, we performed a purely experimental structure analysis for the effective and equilibrium structures of furan. The results highlight the utility of CRASY to obtain rare isotopologue spectra without isotopically enriched samples.
A combined approach to the vibrational characterization of medieval paints on parchment: Handheld Raman spectroscopy and micro‐SORS
Authors: Vieira Márcia , Melo Maria J. , Conti Claudia , Pozzi Federica
Published: January 2024

A careful analytical study of the paint materials used in medieval illuminated manuscripts and their respective formulations is critical to their preservation. Due to their high value and fragile nature, access to these objects is often limited. Therefore, the development of ad‐hoc methodologies allowing researchers to collect data in the least invasive way possible is an essential task in conservation science. This article shows the potential of a combined approach that complements handheld Raman spectroscopy with micro‐SORS for the characterization of medieval paints. This methodology was tested on a reference collection of mock‐up samples prepared as pure, mixture, and layered paints on parchment, based on historical information regarding paint formulations from Iberian scriptoria. Conventional Raman analysis, carried out by means of two handheld spectrometers, was found particularly effective for materials identification in pure paints and multi‐component formulations of increasing complexity. Complementing this data, micro‐SORS proved decisive in differentiating between mixture and layered paints in most mock‐ups examined, yielding detailed information about the stratigraphy of reference samples produced through the overlaying of different paints. This combined methodology may be helpful to researchers who would like to approach the vibrational characterization of paints applied onto fragile artifacts and supports in a totally non‐invasive manner.
A network analysis of Hurricane Maria–related traumatic stress and substance use among Puerto Rican youth
Authors: Vázquez Alejandro L. , Flores Cynthia M. Navarro , Feinberg Daniel K. , Gonzalez Juan Carlos , Young John , Stewart Regan W. , Orengo‐Aguayo Rosaura E.
Published: January 2024

Youth exposed to natural disasters are at risk of developing trauma‐related symptoms as well as engaging in substance use. Although previous research has established associations between disaster‐related stressors and substance use in youth, less has focused on how symptoms of posttraumatic stress disorder (PTSD) may underpin this association. The current study used network analysis to identify specific PTSD symptoms associated with substance use following a natural disaster. Participants were 91,732 youths (Grades 3–12) from across Puerto Rico who completed a needs assessment 5–9 months after Hurricane Maria made landfall in September 2017. We examined associations between PTSD symptoms and substance use, identified clusters of symptoms and bridges between them, and explored age‐ and binary gender–related differences in associations between specific PTSD symptoms and substance use. Analyses identified two symptom communities: (a) arousal and reactivity, negative alterations in cognition and mood, and substance use, and (b) avoidance and intrusion. Broader findings suggested that substance use was most strongly associated with PTSD‐related irritability and angry outbursts among youths. Surrounding nodes explained only 4.1% of the variance in substance use, but this was higher among youths who reported not having a supportive adult, R2 = 8.5; friend, R2 = 7.9; or teacher/counselor, R2 = 7.7, in their life. The bridge symptoms of sleep disruption and physiological reactivity were identified as potentially critical intervention targets for disrupting PTSD symptom networks after a natural disaster. Implications for triaged mental health care following natural disasters and directions for future research are discussed.
Surgical Considerations in Inner Ear Gene Therapy from Human Temporal Bone Anatomy
Authors: Brown Alyssa , Zhu MengYu , Rohani Alireza , Ladak Hanif , Agrawal Sumit K. , Stankovic Konstantina M. , Welling D. Bradley
Published: January 2024

Objective(s)

Recently directed methods of inner ear drug delivery underscore the necessity for understanding critical anatomical dimensions. This study examines anatomical measurements of the human middle and inner ear relevant for inner ear drug delivery studied with three different imaging modalities.

Methods

Post‐mortem human temporal bones were analyzed using human temporal bone histopathology (N = 24), micro computerized tomography (μCT; N = 4), and synchrotron radiation phase‐contrast imaging (SR‐PCI; N = 7). Nine measurements involving the oval and round windows were performed when relevant anatomical structures were visualized for subsequent age‐controlled analysis, and comparisons were made between imaging methods.

Results

Combined human temporal bone histopathology showed the mean distance to the saccule from the center of the stapes footplate (FP) was 2.07 ± 0.357 mm and the minimum distance was 1.23 mm. The mean distance from the round window membrane (RWM) to the osseous spiral lamina (OSL) was 1.75 ± 0.199 mm and the minimum distance was 1.43 mm. Instruments inserted up to 1 mm past the center of the FP are unlikely to cause saccular damage, provided there are no endolymphatic hydrops. Similarly, instruments inserted up to 1 mm through the RWM in the trajectory toward the OSL are unlikely to cause OSL damage.

Conclusion

The combined analyses of inner‐ear dimensions of age‐controlled groups and imaging modalities demonstrate critical dimensions of importance to consider when inserting delivery vehicles into the human cochlea.

Level of Evidence

N/A Laryngoscope, 134:2879–2888, 2024
Social Determinants of Health and Hearing Loss in U.S. Adults
Authors: O'Brien Monica , Danis David O. , Gall Emily , Woods Kelsey , Noonan Kathryn
Published: January 2024

Objectives

Social determinants of health (SDH) are nonmedical, societal factors that influence health. There is limited information on the current relationship between SDH and hearing loss (HL) in the United States. This study aims to compare the odds of HL among US adults by race/ethnicity, education level, income‐to‐poverty level ratio, health insurance coverage, and health care access.

Study Design

Cross‐sectional study.

Methods

The 2015–2020 National Health and Nutrition Examination Survey data were analyzed to compare odds ratios (ORs) for HL, defined as pure tone average over 25 dB HL in at least one ear, by SDH categories using sample weights. Adjusted ORs were calculated using logistic regression models controlling for sex, age, race/ethnicity, education level, income‐to‐federal‐poverty level, health care insurance coverage and access, and loud noise, pesticide, and cigarette exposure.

Results

A total of 6028 participants were included. Non‐Hispanic Black participants had half the odds of HL as Non‐Hispanic White participants (OR 0.52, p < 0.05). Lower education level correlated with higher odds of HL: those without a high school diploma had double the odds of HL compared with college graduates or above (OR 2.05, 1.91, p < 0.05). The income‐to‐federal‐poverty level ratio of 1.3 to less than 2 had higher odds of HL than the 4+ group (OR 1.45, p < 0.05). Use of multiple health care locations was associated with nearly three times the odds of HL than the group using one location (OR 2.87, p < 0.05).

Conclusion

SDH are associated with HL. Further investigation is needed into the mechanism of disparities for targeted prevention and treatment for hearing care equity.

Level of Evidence

IV Laryngoscope, 134:2848–2856, 2024
Uncovering the complex relationship between plant diversity, soil properties, and mycorrhizal inoculum potential in threatened Miombo woodlands
Authors: Kaumbu Jean‐Marc Kyalamakasa , Sene Godar , Stefani Franck , Khasa Damase P.
Published: January 2024

Arbuscular mycorrhizal fungi (AMF) are key members of soil microbial communities and play a key role in regulating ecosystem processes. However, the mutual interdependence of plants and AMF in threatened Miombo woodlands has not yet been fully elucidated. In this study, we investigated the relationship between plant ecological indicators and soil mycorrhizal inoculum potential (MIP) in the Miombo forest fallow of Haut‐Katanga, Democratic Republic of Congo, and identified plant species that positively influence soil MIP. We conducted a floristic inventory on 32 plots and collected soil cores for physicochemical and AMF characterization. Trap cultures using Crotalaria juncea seedlings were performed to determine the soil MIP. We also tested the AMF colonization status of randomly collected living roots of mature woody and dominant herbaceous species to identify explanatory variables for MIP. Our results showed that MIP was twice as high in silty clay soils (63.13%) than in clay soils (30%). Furthermore, MIP increased accordingly with the relative abundance of a group of woody and herbaceous species (e.g., Albizia adianthifolia, Baphia bequaertii, and Setaria pumila) and decreased with others (e.g., Combretum collinum, Harungana madagascariensis and Hyparrhenia diplandra). Linear regressions showed that MIP increased significantly with the specific richness of woody species identified as indicators and with the amount of annual herbs. Woody legumes with high root colonization by AMF appeared to be refuge plants, and primary AMF dispersal vectors, increasing soil MIP. This study provides baseline data that can be used to formulate ecological restoration strategies, including soil and vegetation protection.
Research on the mechanism and application of spatial credit risk contagion based on complex network model
Authors: Ma Junhai , Liu Yuxin , Zhao Li , Liang Weihua
Published: January 2024

Due to information asymmetry, spatial distance will affect the associated credit cooperation relationship among enterprises. This paper employed the real‐world economic data to construct the entropy spatial interaction complex network model, which effectively depicts the associated credit risk among enterprises with the consideration of the influence of spatial distance and regional economic development level. Based on the calculation experiment and the Moran index, this paper reveals the spatial correlation of the credit risk contagion in each region and builds the theoretical model for spatial correlation of credit risk contagion. The research findings indicate the facts as follows. Firstly, enterprises in regions with close spatial proximity or higher level of economic development are more likely to attract enterprises from other regions for cooperation. For instance, due to the close distance between cities and more advanced economy, the eastern coastal region in China presents more intensive enterprise cooperation with other regions. Second, the analysis using the global Moran index reveals a significant spatial credit risk contagion pattern in credit defaults during 2020, attributed to the impact of the COVID‐19 pandemic. Third, the risk contagion effect of long‐distance associated credit is more complex. With the increase of the infection rate of long‐distance linked credit risk, the system will enter a chaotic state, hindering accurate long‐term prediction.
Adaptive Long‐Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4
Authors: Chen Zhongbo , Gustavsson Emil K. , Macpherson Hannah , Anderson Claire , Clarkson Chris , Rocca Clarissa , Self Eleanor , Alvarez Jerez Pilar , Scardamaglia Annarita , Pellerin David , Montgomery Kylie , Lee Jasmaine , Gagliardi Delia , Luo Huihui ,   Genomics England Research Consortium, Hardy John , Polke James , Singleton Andrew B. , Blauwendraat Cornelis , Mathews Katherine D. , Tucci Arianna , Fu Ying‐Hui , Houlden Henry , Ryten Mina , Ptáček Louis J.
Published: January 2024

Background

Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant ataxia with invariable sensory neuropathy originally described in a family with Swedish ancestry residing in Utah more than 25 years ago. Despite tight linkage to the 16q22 region, the molecular diagnosis has since remained elusive.

Objectives

Inspired by pathogenic structural variation implicated in other 16q‐ataxias with linkage to the same locus, we revisited the index SCA4 cases from the Utah family using novel technologies to investigate structural variation within the candidate region.

Methods

We adopted a targeted long‐read sequencing approach with adaptive sampling on the Oxford Nanopore Technologies (ONT) platform that enables the detection of segregating structural variants within a genomic region without a priori assumptions about any variant features.

Results

Using this approach, we found a heterozygous (GGC)n repeat expansion in the last coding exon of the zinc finger homeobox 3 (ZFHX3) gene that segregates with disease, ranging between 48 and 57 GGC repeats in affected probands. This finding was replicated in a separate family with SCA4. Furthermore, the estimation of this GGC repeat size in short‐read whole genome sequencing (WGS) data of 21,836 individuals recruited to the 100,000 Genomes Project in the UK and our in‐house dataset of 11,258 exomes did not reveal any pathogenic repeats, indicating that the variant is ultrarare.

Conclusions

These findings support the utility of adaptive long‐read sequencing as a powerful tool to decipher causative structural variation in unsolved cases of inherited neurological disease. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.