bluuebunny/crossref_metadata_2025 huggingface dataset:
Incremental value of magnification and indocyanine green for parathyroid preservation in thyroid surgery
Authors: Shaphaba Konthoujam , Thakar Alok , Sakthivel Pirabu , Sikka Kapil , Singh Chirom Amit , Kumar Rajeev , Chandran Ashwin , Goswami Ravinder
Published: May 2023

Background

To assess the promise of surgical magnification and of intraoperative indocyanine green (ICG) assisted near‐infrared fluorescence (NIRF) in improving parathyroid identification and viability assessment during thyroidectomy.

Methods

Prospective comparative study. Parathyroid gland identification sequentially assessed by naked eye, surgical microscopy, and by NIRF imaging following ICG administration (5 mgIV). Parathyroid perfusion/vitality reassessed end‐surgery by ICG‐NIRF.

Results

An expected total of 104 parathyroid glands were assessed in 35 patients (17 total‐thyroidectomy, 18 hemi‐thyroidectomy). 54/104 (51.9%) were identified by naked eye, and sequentially greater numbers identified by microscope magnification (n = 61; 58.7%; p = 0.33), and by ICG‐NIRF (n = 72; 69.2%; p = 0.01). ICG‐NIRF detected additional parathyroid glands in 16/35 patients (45.7%). Confident identification of at least one parathyroid remained unachieved in 5/35 by naked eye, in 4/35 by microscopic magnification, and in no patient by ICG‐NIRF. ICG‐NIRF indicated end‐of‐surgery devascularization in 12/72 glands and informed decisions regarding gland implantation.

Conclusion

Significantly greater parathyroid glands are identified and preserved with surgical magnification and with ICG‐NIRF. Both techniques merit routine adoption for thyroidectomy.
Structural Insights into Electrophiles and Electrophilic Metabolites Sensing and Signaling: The Missing Information
Authors: Rogg Chloé , Aye Yimon
Published: May 2023

Native reactive electrophilic species (RES) are long‐recognized regulators of pathophysiology; yet, knowledge surrounding how RES regulate context‐specific biology remains limited. The latest technological advances in profiling and precision decoding of RES sensing and signaling have begun to bring about improved understanding of localized RES regulatory paradigms. However, studies in purified systems — prerequisites for gaining structure/function insights — prove challenging. We here introduce emerging chemical biology tools available to probe RES signaling, and the new knowledge that these tools have brought to the field. We next discuss existing structural data of RES‐sensor proteins complexed with electrophilic metabolites or small molecule drugs (limited to <300 Da), including challenges faced in acquiring homogenous RES‐bound proteins. We further offer considerations that could promote enhanced understanding of RES regulation derived from three‐dimensional structures of RES‐modified proteins.
In search of a measure to investigate mental performance among children: Development of the mental speed test
Authors: Avcı‐Doğan Gülşah , Akbulut Yavuz , Sak Uğur
Published: May 2023

Processing speed is a component of general intelligence and an indicator of learning potential. There is a need for robust measures of mental speed based on contemporary theoretical developments. The current study addressed this need by proposing a mental speed test for children aged 60 to 96 months (5 to 8 years) and examining its psychometric properties. The test included indicators of perceptual speed, memory speed, reasoning speed, and fluency‐flexibility speed presented through nonverbal items administered individually using touchscreen tablets. After establishing gender non‐bias and concurrent validity with a contemporary intelligence test (i.e., ASIS, r = .59) with 107 children, the next administration included 373 children. Exploratory factor analysis (EFA) with subtest scores revealed a single‐factor structure accounting for 45% of the total variance. Additional data from 212 children were used to assess structural validity and gender bias, which showed acceptable goodness of fit, providing evidence of the validity and reliability of the new measure for further use.
Acetic acid‐induced colitis modulating potential of total crude alkaloidal extract ofPicralima nitidaseeds in rats
Authors: Otu‐Boakye Sarah A. , Yeboah Kofi O. , Boakye‐Gyasi Eric , Oppong‐Kyekyeku James , Okyere Prince D. , Osafo Newman
Published: May 2023

Purpose

The total crude alkaloidal extract ofPicralima nitidaseeds (PNE) is known to possess anti‐inflammatory activity among other therapeutic benefits although its benefits in colitis has not been investigated. The current study therefore seeks to investigate the anti‐colitis potential of PNE using acetic acid‐induced colitis model in rats.

Methods

Sprague Dawley rats were treated with oral 500 mg/kg sulphasalazine or 30, 100, and 300 mg/kg of PNE daily for 8 days with induction of colitis on the fourth day with acetic acid. Rats were killed 24 h after the last treatment and whole blood was obtained from the jugular vein for hematological analysis and biochemical assays. Colons were extirpated for assessment of macroscopic and histological damage to the colon.

Results

Treatment with PNE protected against colonic injury induced with acetic acid by decreasing mucosal ulceration, epithelial erosion, inflammatory cell infiltration, and colonic edema. Thus, PNE preserved mucosal architecture and suppressed goblet cells depletion. Moreover, treatment with PNE was associated with improved hematological parameters and reductions in the expression of serum tumor necrosis factor‐alpha, interleukin‐1β, and p38 mitogen‐activated protein kinase. Also, PNE treatment exerted antioxidant effects by reducing nitric oxide production and increasing glutathione levels. In addition, PNE inhibited colonic lipid peroxidation by decreasing myeloperoxidase activity and malondialdehyde production.

Conclusion

It can be concluded that PNE attenuates intestinal oxidative and inflammatory damages following intrarectal acetic acid challenge. Thus, demonstrates potential for use in chronic intestinal inflammatory diseases such as ulcerative colitis.
Ocular manifestations in Iranian patients referred to rheumatology clinics from 2018 to 2020
Authors: Pournazari Meharan , Hashemi Tara , Zarpoosh Mahsa , Amirian Parsa
Published: May 2023

Aim

Autoimmune diseases are presented with many signs and symptoms. Eyes are commonly involved in these diseases. This study aimed to estimate the prevalence of different ophthalmological complications in patients with and without immune‐mediated rheumatological diseases.

Methods

Patients who were referred to Kermanshah's rheumatologic clinics by an ophthalmologist from 2018 to 2020 for a rheumatologist visit were included. A checklist for extracting data from medical files; containing symptoms, organ involvement, ocular diseases diagnosed by an ophthalmologist, rheumatologic diseases diagnosed by a rheumatologist, lab tests, and disease progression was created. After we evaluated the medical data, we found that 54 patients out of 106 were diagnosed to have immune‐mediated rheumatological diseases. Patients were divided into two groups; the first group included patients with diagnosed immune‐mediated rheumatologic disease and ophthalmic complications; patients with no known immune‐mediated rheumatological disease were considered the second group. The obtained information was analyzed using statistical tests.

Results

One hundred and six patients participated in this study, 67% of whom were females. The most common ocular symptom was blurred vision (49%). Involvement of both eyes (43.4%) was more common than single left or right eye involvement. The most common ophthalmic disease was anterior uveitis (35.8%). The most common rheumatologic disease was Behçet's disease (21.7%). Hypertension and hypothyroidism were the most common comorbidities; 36.7% of the patients had skin and mucous involvement, and 37.7% had joint involvement. In follow‐up of the ophthalmic symptoms, most patients were controlled partially. Ophthalmic diseases, laboratory tests, joint involvement, skin and mucous involvement, and lung involvement were associated with rheumatologic diseases.

Conclusion

Early diagnosis of ocular involvement in rheumatologic diseases is crucial to prevent adverse complications. The results can be beneficial for a better perception of ophthalmic symptoms and diseases among patients with autoimmune diseases.
Vulvodynia: A practical guide in treatment strategies
Authors: Santangelo Giusi , Ruggiero Gianfilippo , Murina Filippo , Di Donato Violante , Perniola Giorgia , Palaia Innocenza , Fischetti Margherita , Casorelli Assunta , Giannini Andrea , Di Dio Camilla , Muzii Ludovico , Benedetti Panici Pierluigi , Bogani Giorgio
Published: May 2023

Vulvodynia is a debilitating condition characterized by chronic vulvar pain, with a detrimental impact on the patient's overall quality of life. Its etiology is multifactorial, but still in the process of being clearly outlined. Vulvodynia is not a single entity. It is a heterogeneous condition characterized by multiple triggers, making it challenging to define a reference standard for its treatment. In this manuscript we selected all articles including the following key criteria: “vulvodynia”. The primary outcomes observed included the resolution of chronic pelvic pain, dyspareunia and sexual satisfaction, psychological well‐being, and overall quality of life. Most pharmacologic treatments require further evidence to be recommended. On the other hand, non‐pharmacologic approaches such as psychotherapy, physical therapy, and surgery have received stronger support. This review summarizes pros and cons of adopting available treatments. Multimodal approaches should be introduced to improve patient outcomes. Further investigations are warranted to improve patients' quality of life.
Vaginal changes after ovariectomy in ewes: A large animal model for genitourinary syndrome of menopause
Authors: Vodegel Eva V. , Guler Zeliha , Ras Lamees , Mackova Katerina , Groeneveld Anne C. H. M. , Bezuidenhout Deon , Deprest Jan , Jeffery Stephen T. , Roovers Jan‐Paul W. R.
Published: May 2023

Objective

To evaluate the effect of iatrogenic menopause on the physiology of the vagina of the ewe and to evaluate if vaginal changes in ewes can be translated to women with genitourinary syndrome of menopause (GSM).

Methods

Preclinical research with Dohne Merino ewes. Iatrogenic menopause was induced by bilateral ovariectomy (OVX). Animals were randomized for surgery, blinded for allocation and outcome assessment. Differences between groups were determined by linear regression analyses at 5 months after OVX. Outcome measures were vaginal epithelial thickness, pH, vaginal maturation value, vaginal maturation index, epithelial glycogen accumulation, content of elastin fibers, collagen, and vascularity.

Results

OVX ewes (n = 20) showed epithelial thinning of the vaginal wall from 146 μm to 47 μm (mean, P < 0.001). Furthermore, epithelial glycogen accumulation and vascularity of the vaginal wall significantly decreased (43% and 23%, respectively) as compared with the control group (no intervention; n = 5). No significant differences were found for other outcome measures.

Conclusion

This study established the ewe as a suitable large animal model for GSM. Furthermore, the similar relevant outcomes in humans and ewes hold great value for future translational research for the evaluation and optimization of different treatment modalities for GSM.
Primitive C4 ${C}_{4}$‐decompositions of Kn−I ${K}_{n}-I$
Authors: Schroeder Michael W.
Published: May 2023

A decomposition of a graph is primitive if no proper, nontrivial subset of is a decomposition of an induced subgraph of . An unresolved question posed by Asplund et al. in a recent publication involves the existence of primitive decompositions of cocktail party graphs into cycles of length 4, which is resolved by this paper.
Mean value splines and their use for climatological time series
Authors: Steinacker Reinhold
Published: May 2023

A new approach of splines to examine climatological time series is introduced and different applications are shown. Instead of the classical spline‐procedure to find polynomials which fit given values at certain points (knots), a variational formulation is used here, where a cost function is minimized to obtain smooth interpolated values at arbitrary points. The innovation of the method consists in the selection of the constraint, namely the conservation of mean values within certain smoothing intervals. The methodology allows a sound derivation of the past and present climate conditions in times of climate change. It allows a refined computation of extreme values and of the probability of certain temperature thresholds. The methodology furthermore allows to detect break points in climatological time series. Finally the method leads to a consistent interpolation of time series, which are only given by mean values. Several applications of the method, using climatological time series of Vienna are shown and discussed.
PAI‐1 mediates TGF‐β1‐induced myofibroblast activation in tenocytes via mTOR signaling
Authors: Alenchery Rahul G. , Ajalik Raquel E. , Jerreld Kyle , Midekksa Firaol , Zhong Sylvia , Alkatib Bashar , Awad Hani A.
Published: May 2023

Transforming growth factor‐beta (TGF‐β1) induces plasminogen activator inhibitor 1 (PAI‐1) to effect fibrotic pathologies in several organs including tendon. Recent data implicated PAI‐1 with inhibition of phosphatase and tensin homolog (PTEN) suggesting that PAI‐1‐induced adhesions involves phosphoinositide 3‐kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling. Ergo, we investigated effects of TGF‐β1, PAI‐1, and mTOR signaling crosstalk on myofibroblast activation, senescence, and proliferation in primary flexor tenocytes from wild‐type (WT) and PAI‐1 knockout (KO) mice. PAI‐1 deletion blunted TGF‐β1‐induced myofibroblast activation in murine flexor tenocytes and increased the gene expression of Mmp‐2 to confer protective effects against fibrosis. While TGF‐β1 significantly reduced phosphorylation of PTEN in WT cells, PAI‐1 deletion rescued the activation of PTEN. Despite that, there were no differences in TGF‐β1‐induced activation of mTOR signaling (AKT, 4EBP1, and P70S6K) in WT or KO tenocytes. Phenotypic changes in distinct populations of WT or KO tenocytes exhibiting high or low mTOR activity were then examined. TGF‐β1 increased alpha‐smooth muscle actin abundance in WT cells exhibiting high mTOR activity, but this increase was blunted in KO cells exhibiting high 4EBP1 activity but not in cells exhibiting high S6 activity. DNA damage (γH2AX) was increased with TGF‐β1 treatment in WT tenocytes but was blunted in KO cells exhibiting high mTOR activity. Increased mTOR activity enhanced proliferation (Ki67) in both WT and KO tenocytes. These findings point to a complex nexus of TGF‐β1, PAI‐1, and mTOR signaling in regulating proliferation, myofibroblast differentiation, and senescence in tenocytes, which could define therapeutic targets for chronic tendon adhesions and other fibrotic pathologies.
Load analysis of hands and feet while using different types of crutches with various leg's weight bearing
Authors: Stievano Simona , Roesch Friederike , Prommersberger Karl‐Josef , Fuhrmann Renee , Mühldorfer‐Fodor Marion
Published: May 2023

The study aimed to define the load on hands using various commonly used types of crutches while walking with a full load on both legs (FL), with 20 kg partial load (PL), or with the left leg wholly unloaded (UL). Twenty‐six healthy subjects used crutches with ergonomic handles, with anatomic handles (wider and softer bearing surface), and arthritis crutches (horizontal supporting area for the forearm). Sensor mats between hand and handles continuously measured the load transmitted, while sensor soles in the shoes recorded the ground reaction forces simultaneously. The load on the palm and separately the radial and ulnar halves of the palm were analyzed. With arthritis crutches, significantly lower load was transferred to the hands compared to forearm crutches (FL 3% vs. 25% of body weight, PL 8% vs. 87%, UL 12% vs. 103%). The load on hands increased significantly from FL to PL and UL for both types of crutches. The ipsilateral left hand had to bear significantly more load than the right hand. However, the feet's time‐ground reaction curves showed more irregularities, and PL on the left leg was significantly higher with arthritis crutches. Anatomic handles reduced the load on the ulnar half of the palm (FL 3% vs. 5%, PL 13% vs. 18%, UL 17% vs. 23%); the radial half of the palm had a similar load to bear with both types of handles (11/11%, 31/32%, 34/35%). Arthritis crutches allow unburdening hands at the expense of gait stability. Anatomic handles reduce the load on the Guyon's canal.
Quantification of peptide components in cinobufacini injection and toad skin by ultra‐high‐performance liquid chromatography/triple quadrupole mass spectrometry
Authors: Zhang Xinwen , Lv Xiang , Qian Dong , Li Junxian , Qian Yi , Wang Jiaojiao , Zhu Yuyu , Zhou Jing , Ma Hongyue
Published: May 2023

Cinobufacini injection is commonly used in the clinical treatment of tumors and hepatitis B, but the quality is uneven. Currently, the main focus of its quality assessment is on steroids and alkaloids. Based on a previous study, we screened four peptides with high reproducibility, responsiveness, and specificity. This research was the first to develop an ultra‐high‐performance liquid chromatography/triple quadrupole mass spectrometry approach for evaluating the quality of cinobufacini preparations from the peptide perspective. In this study, we have identified 230 peptides in cinobufacini injection by Q‐Exactive mass spectrometry, which contains species‐specific peptides. Then, we used ultra‐high‐performance liquid chromatography/triple quadrupole mass spectrometry to establish a quantitative method for species‐specific peptides and carried out method validation. The result revealed that four peptides were linear in a specific range, and had great reproducibility, accuracy, and stability. Eventually, we evaluated the quality of eight batches of cinobufacini injections and 26 batches of toad skins using the total content of target peptides as the criterion. The outcomes demonstrated that the quality of cinobufacini injection is generally stable and the toad skin from Shandong is of the best quality. In conclusion, the quantitative approach that focuses on peptides will offer innovative perspectives on assessing the quality of cinobufacini preparations.
Effect of Life Review Therapy for Holocaust Survivors: A randomized controlled trial
Authors: Forstmeier Simon , Zimmermann Sarah , van der Hal Elisheva , Auerbach Martin , Kleinke Kristian , Maercker Andreas , Brom Danny
Published: May 2023

Despite the therapeutic needs of aging Holocaust survivors, no randomized controlled trial (RCT) of psychotherapy exists for this population, with very few on older adults in general. This RCT aimed to compare the efficacy of Life Review Therapy for Holocaust survivors (LRT‐HS) relative to a supportive control group. Holocaust survivors with a probable diagnosis of full or subsyndromal posttraumatic stress disorder (PTSD) or depressive disorder were included. Exclusion criteria were probable dementia, acute psychotic disorder, and acute suicidality. The predefined primary endpoint was the course of PTSD symptom scores. In total, 49 of 79 consecutive individuals assessed for eligibility were randomized and included in the intent‐to‐treat analyses (LRT‐HS: n = 24, control: n = 25; Mage = 81.5 years, SD = 4.81, 77.6% female). Linear mixed models revealed no statistically significant superiority of LRT‐HS for PTSD symptoms at posttreatment, with moderate effect sizes, Time x Condition interaction: t(75) = 1.46, p = .148, dwithin = 0.70, dbetween = 0.41, but analyses were significant at follow‐up, with large effect sizes, t(79) = 2.89, p = .005, dwithin = 1.20, dbetween = 1.00. LRT‐HS superiority for depression was observed at posttreatment, t(73) = 2.58, p = .012, but not follow‐up, t(76) = 1.08, p = .282, with moderate effect sizes, dwithin = 0.46–0.60, dbetween = 0.53–0.70. The findings show that even in older age, PTSD and depression following exposure to multiple traumatic childhood events can be treated efficaciously using an age‐appropriate treatment that includes structured life review and narrative exposure.
Atopic eczema patients and healthcare professionals join forces in Malta
Authors: Stalder Jean‐François , Aubert Hélène , Barbarot Sebastien , Chavigny Jean‐Marc , Deleuran Mette , Eichenfield Lawrence F. , El Hachem May , Lio Peter , Marcoux Danielle , Roxburgh Christine , Saint Aroman Markéta , Sentenac Fanny , Taieb Alain , Thormann Kathrin , Vestergaard Christian , Wiener‐Hemme Gabriele , Wollenberg Andreas
Published: May 2023

Atopic patients, multi‐disciplinary specialists, caregivers, and experts from all over the world participated in the International Meeting of the Eczema Foundation in Malta (IMEF). During this 4‐day conference, attendants addressed the challenges pertaining to the management of atopic dermatitis by sharing their experience in the form of presentations, discussion sessions, workshops, and a plenary session. This article aims to report on what we consider to be a successful attempt to unite patients and caregivers in the quest for improved treatment of atopic dermatitis through the implementation of therapeutic patient education.
Widely Tunable Femtosecond Sources with Continuously Tailorable Bandwidth Enabled by Self‐Phase Modulation
Authors: Chou Lu‐Ting , Hung Hao‐Hsuan , Liu Ai‐Yin , Wu Shao‐Hsuan , Jang Je‐Chi , Zhong Dong‐Lin , Hsiao Hui‐Hsin , Chia Shih‐Hsuan
Published: May 2023

Generating ultrafast pulses with better spectrotemporal control is crucial for optimizing and characterizing nonlinear light–matter responses, yet it is limited by the gain bandwidth of laser media or the phase‐matching geometry of nonlinear processes. This work proposes a simple approach to independently manage a femtosecond source's spectral location and bandwidth. Self‐phase‐modulation‐enabled spectral broadening is first analyzed, which is potentially energy‐scalable using hollow‐core capillaries or multipass cells. It is demonstrated that the outmost lobes in the broadened spectrum show different dependencies on the initial pulse energy and duration. A simple yet effective toy model is introduced that successfully predicts broadband spectral tuning, and the impact of other nonlinear effects, dispersion, and input pulse asymmetry on the experimental scenario is also discussed. Thus a fiber‐based versatile source is demonstrated, which is compressible down to its transform‐limit duration, as short as 12.2 fs centered at 920 nm. In addition, bandwidth‐dependent third‐harmonic generation spectroscopy is performed from a dielectric metasurface with an optimized nonlinear response, and the dependency of laser bandwidth and pulse duration is investigated on the signal‐to‐background ratio of two‐photon images. It is believed that this demonstration will advance the investigation of bandwidth‐dependent nonlinear spectroscopy and microscopy.
Statistical approaches applicable in managing OMICS data: Urinary proteomics as exemplary case
Authors: An De‐Wei , Yu Yu‐Ling , Martens Dries S. , Latosinska Agnieszka , Zhang Zhen‐Yu , Mischak Harald , Nawrot Tim S. , Staessen Jan A.
Published: May 2023

With urinary proteomics profiling (UPP) as exemplary omics technology, this review describes a workflow for the analysis of omics data in large study populations. The proposed workflow includes: (i) planning omics studies and sample size considerations; (ii) preparing the data for analysis; (iii) preprocessing the UPP data; (iv) the basic statistical steps required for data curation; (v) the selection of covariables; (vi) relating continuously distributed or categorical outcomes to a series of single markers (e.g., sequenced urinary peptide fragments identifying the parental proteins); (vii) showing the added diagnostic or prognostic value of the UPP markers over and beyond classical risk factors, and (viii) pathway analysis to identify targets for personalized intervention in disease prevention or treatment. Additionally, two short sections respectively address multiomics studies and machine learning. In conclusion, the analysis of adverse health outcomes in relation to omics biomarkers rests on the same statistical principle as any other data collected in large population or patient cohorts. The large number of biomarkers, which have to be considered simultaneously requires planning ahead how the study database will be structured and curated, imported in statistical software packages, analysis results will be triaged for clinical relevance, and presented.
Histone deacetylase inhibitor belinostat regulates metabolic reprogramming in killing KRAS‐mutant human lung cancer cells
Authors: Peter Rebecca M. , Sarwar Md. Shahid , Mostafa Sarah Z. , Wang Yujue , Su Xiaoyang , Kong Ah‐Ng
Published: May 2023

Kirsten rat sarcoma virus (KRAS) oncogene, found in 20%–25% of lung cancer patients, potentially regulates metabolic reprogramming and redox status during tumorigenesis. Histone deacetylase (HDAC) inhibitors have been investigated for treating KRAS‐mutant lung cancer. In the current study, we investigate the effect of HDAC inhibitor (HDACi) belinostat at clinically relevant concentration on nuclear factor erythroid 2‐related factor 2 (NRF2) and mitochondrial metabolism for the treatment of KRAS‐mutant human lung cancer. LC‐MS metabolomic study of belinostat on mitochondrial metabolism was performed in G12C KRAS‐mutant H358 non‐small cell lung cancer cells. Furthermore, l‐methionine (methyl‐13C) isotope tracer was used to explore the effect of belinostat on one‐carbon metabolism. Bioinformatic analyses of metabolomic data were performed to identify the pattern of significantly regulated metabolites. To study the effect of belinostat on redox signaling ARE‐NRF2 pathway, luciferase reporter activity assay was done in stably transfected HepG2‐C8 cells (containing pARE‐TI‐luciferase construct), followed by qPCR analysis of NRF2 and its target gene in H358 cells, which was further confirmed in G12S KRAS‐mutant A549 cells. Metabolomic study reveals significantly altered metabolites related to redox homeostasis, including tricarboxylic acid (TCA) cycle metabolites (citrate, aconitate, fumarate, malate, and α‐ketoglutarate); urea cycle metabolites (Arginine, ornithine, argino‐succinate, aspartate, and fumarate); and antioxidative glutathione metabolism pathway (GSH/GSSG and NAD/NADH ratio) after belinostat treatment. 13C stable isotope labeling data indicates potential role of belinostat in creatine biosynthesis via methylation of guanidinoacetate. Moreover, belinostat downregulated the expression of NRF2 and its target gene NAD(P)H:quinone oxidoreductase 1 (NQO1), indicating anticancer effect of belinostat is mediated, potentially via Nrf2‐regulated glutathione pathway. Another HDACi panobinostat also showed potential anticancer effect in both H358 and A549 cells via Nrf2 pathway. In summary, belinostat is effective in killing KRAS‐mutant human lung cancer cells by regulating mitochondrial metabolism which could be used as biomarkers for preclinical and clinical studies.
TXNL4B regulates radioresistance by controlling the PRP3‐mediated alternative splicing of FANCI
Authors: Ju Zhao , Xiang Jing , Xiao Liang , He Yan , Zhang Le , Wang Yin , Lei Ridan , Nie Yunfeng , Yang Long , Miszczyk Justyna , Zhou Pingkun , Huang Ruixue
Published: May 2023

Ionizing radiation (IR) has been extensively used for cancer therapy, but the radioresistance hinders and undermines the radiotherapy efficacy in clinics greatly. Here, we reported that the spliceosomal protein thioredoxin‐like 4B (TXNL4B) is highly expressed in lung tissues from lung cancer patients with radiotherapy. Lung cancer cells with TXNL4B knockdown illustrate increased sensitivity to IR. Mechanistically, TXNL4B interacts with RNA processing factor 3 (PRP3) and co‐localizes in the nucleus post‐IR. Nuclear localization of PRP3 promotes the alternative splicing of the Fanconi anemia group I protein (FANCI) transcript variants, FANCI‐12 and FANCI‐13. PRP3 regulates alternative splicing of FANCI toward the two variants, FANCI‐12 and FANCI‐13. Radioresistance was greatly enhanced through the combination of PRP31 and PRP8, the critical components of core spliceosome promoted by PRP3. Notably, the inhibition of PRP3 to suppress the production of FANCI‐12 would deprive PRP31 and PRP8 of such interaction. As a result, cell cycle G2/M arrest was induced, DNA damage repair was delayed, and radiosensitivity was improved. Collectively, our study highlights potential novel underlying mechanisms of the involvement of TXNL4B and alternative splicing in radioresistance. The results would benefit potential cancer radiotherapy.
The downside of artificial intelligence (AI) in green choices: How AI recommender systems decrease green consumption
Authors: Wang Kai , Lu Lin , Fang Junyi , Xing Yiwei , Tong Zelin , Wang Lei
Published: May 2023

Extant research shows that marketers are increasingly utilizing artificial intelligence (AI) recommender systems to aid consumers in purchasing decisions across various products, but little research has examined the potential negative impact of AI recommenders on consumers' green consumption intentions compared with human recommender. To address this gap, three studies reveal that AI (vs. human) recommenders reduce consumers' motivation for impression management in green consumption contexts, resulting in decreased intention to purchase green products. This negative effect of AI recommenders on green consumption can be mitigated by priming consumer's environmental identity. This research contributes to the literature of green consumption and AI usage, while also providing practical implications for marketers to manage consumer's reduced green consumption intentions resulting from AI recommenders.
Optimal contract design for live streaming platforms under dual asymmetric information considering corporate social responsibility
Authors: Zhang Wenqian , Wang Haiyan
Published: May 2023

When live streamers sell products to consumers on live streaming platforms, their abilities and service efforts are private, and thus, the issues of identifying their true abilities, motivating them to use appropriate service efforts, and providing a mechanism to allocate profits remain to be resolved for live streaming platforms. Adopting a principal–agent model, we investigate the optimal contract design between a live streaming platform and live streamers. In addition, we study the impacts of the price and service competition between live streamers and the platform's corporate social responsibility on the optimal contract design. The results show that high commission rates and low signing bonuses are not always beneficial to platforms, and the optimal contract design to identify the types of live streamers can make it more profitable. In addition, the utility‐maximizing platform always sets lower commission rates and signing bonuses compared with the profit‐maximizing platform. Regardless of the platform's goal, total profits and commission rates are higher under competition compared with no competition. For the government, policies and subsidies should be provided, such as regulating commission rates by setting a limited range and increasing subsidies for the marginal costs of live streaming platforms, which can effectively motivate live streaming platforms to enhance corporate social responsibility.
Recanalize ureteral stents with focused ultrasound
Authors: Singh Rohit , Samaddar Abhirup , Duchene David , Waller Stephen , Yang Xinmai
Published: May 2023

Background

Maintaining ureteral patency is imperative to preventing renal injury and systemic infection. Ureteral stents are small conduits connecting the kidney and the bladder. They have been widely used to treat ureteral obstructions and ureteral leaks. The most problematic and frequent stent‐associated complication is stent encrustation. This occurs when mineral crystals (e.g. calcium, oxalate, phosphorus, struvite) are deposited onto the surface and internal lumen of the stent. Encrustation can lead to the obstruction of a stent and increases risk of systemic infection. As a result, ureteral stents need to be replaced typically every 2–3 months.

Purpose

In this study, we present a non‐invasive, high‐intensity focused ultrasound (HIFU)‐based technique to recanalize obstructed stents. By taking advantage of the mechanical force produced by a HIFU beam, including acoustic radiation force, acoustic streaming, and cavitation, HIFU can break up encrustations, clearing the stent of obstruction.

Methods

The ureteral stents for this study were obtained from patients undergoing ureteral stent removal. Under the guidance of ultrasound imaging, the encrustation in the stents were located, and then targeted by HIFU at frequencies of 0.25 and 1 MHz. The duty cycle of HIFU was 10%, and the HIFU burst repetition rate was 1 Hz, while the HIFU amplitude was varied to find the threshold pressure that would displace encrustations. The treatment duration was limited at 2 min (or 120 shots from HIFU). The treatments were carried out in two different orientations (parallel and perpendicular) of the ureteral stent with respect to the HIFU beam. For each setting, five treatments were conducted for a maximum duration of 2 min. During the entire treatment, an ultrasound imaging system was used to monitor the movement of encrustations inside the stent. The peak negative HIFU pressures needed to move the encrustations inside the stent was recorded for quantitative analysis.

Results

Our results demonstrated that at both 0.25 and 1 MHz ultrasound frequencies, obstructed stents could be recanalized. At 0.25 MHz, the needed average peak negative pressure was 0.52 MPa in parallel orientation and 0.42 MPa in perpendicular orientation. At 1 MHz, the needed average peak negative pressure was 1.10 MPa in parallel orientation and 1.15 MPa in perpendicular orientation

Conclusions

This first in‐vitro study has demonstrated the feasibility of non‐invasive HIFU to recanalize ureteral stents. This technology has a potential to reduce the need for ureteral stent exchange.
Axon fiber orientation as the source of T1 relaxation anisotropy in white matter: A study on corpus callosum in vivo and ex vivo
Authors: Kauppinen Risto A. , Thothard Jeromy , Leskinen Henri P. P. , Pisharady Pramod K. , Manninen Eppu , Kettunen Mikko , Lenglet Christophe , Gröhn Olli H. J. , Garwood Michael , Nissi Mikko J.
Published: May 2023

Purpose

Recent studies indicate that T1 in white matter (WM) is influenced by fiber orientation in B0. The purpose of the study was to investigate the interrelationships between axon fiber orientation in corpus callosum (CC) and T1 relaxation time in humans in vivo as well as in rat brain ex vivo.

Methods

Volunteers were scanned for relaxometric and diffusion MRI at 3 T and 7 T. Angular T1 plots from WM were computed using fractional anisotropy and fiber‐to‐field‐angle maps. T1 and fiber‐to‐field angle were measured in five sections of CC to estimate the effects of inherently varying fiber orientations on T1 within the same tracts in vivo. Ex vivo rat‐brain preparation encompassing posterior CC was rotated in B0 and T1, and diffusion MRI images acquired at 9.4 T. T1 angular plots were determined at several rotation angles in B0.

Results

Angular T1 plots from global WM provided reference for estimated fiber orientation–linked T1 changes within CC. In anterior midbody of CC in vivo, where small axons are dominantly present, a shift in axon orientation is accompanied by a change in T1, matching that estimated from WM T1 data. In CC, where large and giant axons are numerous, the measured T1 change is about 2‐fold greater than the estimated one. Ex vivo rotation of the same midsagittal CC region of interest produced angular T1 plots at 9.4 T, matching those observed at 7 T in vivo.

Conclusion

These data causally link axon fiber orientation in B0 to the T1 relaxation anisotropy in WM.
Deuterium echo‐planar spectroscopic imaging (EPSI) in the human liver in vivo at 7 T
Authors: Nam Kyung Min , Gursan Ayhan , Bhogal Alex A. , Wijnen Jannie P. , Klomp Dennis W. J. , Prompers Jeanine J. , Hendriks Arjan D.
Published: May 2023

Purpose

To demonstrate the feasibility of deuterium echo‐planar spectroscopic imaging (EPSI) to accelerate 3D deuterium metabolic imaging in the human liver at 7 T.

Methods

A deuterium EPSI sequence, featuring a Hamming‐weighted k‐space acquisition pattern for the phase‐encoding directions, was implemented. Three‐dimensional deuterium EPSI and conventional MRSI were performed on a water/acetone phantom and in vivo in the human liver at natural abundance. Moreover, in vivo deuterium EPSI measurements were acquired after oral administration of deuterated glucose. The effect of acquisition time on SNR was evaluated by retrospectively reducing the number of averages.

Results

The SNR of natural abundance deuterated water signal in deuterium EPSI was 6.5% and 5.9% lower than that of MRSI in the phantom and in vivo experiments, respectively. In return, the acquisition time of in vivo EPSI data could be reduced retrospectively to 2 min, beyond the minimal acquisition time of conventional MRSI (of 20 min in this case), while still leaving sufficient SNR. Three‐dimensional deuterium EPSI, after administration of deuterated glucose, enabled monitoring of hepatic glucose dynamics with full liver coverage, a spatial resolution of 20 mm isotropic, and a temporal resolution of 9 min 50 s, which could retrospectively be shortened to 2 min.

Conclusion

In this work, we demonstrate the feasibility of accelerated 3D deuterium metabolic imaging of the human liver using deuterium EPSI. The acceleration obtained with EPSI can be used to increase temporal and/or spatial resolution, which will be valuable to study tissue metabolism of deuterated compounds over time.
Concordance between patient‐ and physician‐reported Myasthenia Gravis Activities of Daily Living (MG‐ADL) scores
Authors: Dewilde Sarah , Janssen M. F. , Tollenaar Nafthali H. , Vanoli Fiammetta , Frangiamore Rita , Phillips Glenn , Paci Sandra , Mantegazza Renato , Meisel Andreas , Stascheit Frauke
Published: May 2023

Introduction/Aims

Myasthenia gravis (MG) is a neuromuscular disease characterized by abnormal skeletal muscle fatiguability. The MG Activities of Daily Living (MG‐ADL) scale assesses eight symptoms and is often used as primary endpoint in MG clinical trials where it is completed by neurologists. However, in observational studies, patients frequently complete the MG‐ADL scale independently of their neurologist. In this study we aimed to assess the concordance between self‐ and physician‐reported MG‐ADL scores.

Methods

An international observational study was conducted among adult patients with MG scheduled for a routine visit or who entered the hospital via emergency services. Consenting patients and physicians completed the MG‐ADL. Concordance between assessments was calculated using Gwet's agreement coefficient (Gwet's AC) for the MG‐ADL individual items and the intraclass correlation coefficient (ICC) for the MG‐ADL total score.

Results

Data were collected from 137 patients (63% female; mean age, 57.7 years). Physicians assessed the patient's symptoms as slightly more severe (8.1 vs 7.5 MG‐ADL total score, respectively), corresponding to a difference of 0.6 on a range from 0 to 24. The ICC for the MG‐ADL total score between the patient and the physician assessment was 0.94 (95% confidence interval, 0.89 to 0.95), showing excellent concordance. Gwet's AC showed substantial to almost perfect agreement for all items, except eyelid droop, for which the agreement was moderate.

Discussion

Our results demonstrate that patients and neurologists have a concordant assessment of the patient's MG symptoms when using the MG‐ADL scale. This evidence supports patient self‐administration of the MG‐ADL in clinical practice and research.
Remodeling of the neuromuscular junction in myasthenia gravis increases serum neurofilament heavy chain levels
Authors: Wong Sui H. , Petzold Axel
Published: May 2023

Introduction/Aims

In myasthenia gravis, prolonged muscle denervation causes muscle atrophy. We re‐visited this observation using a biomarker hypothesis. We tested if serum neurofilament heavy chain levels, a biomarker for axonal degeneration, were elevated in myasthenia gravis.

Methods

We enrolled 70 patients with isolated ocular myasthenia gravis and 74 controls recruited from patients in the emergency department. Demographic data were collected alongside serum samples. Serum samples were analyzed by enzyme‐linked immunosorbent assay (ELISA) for the neurofilament heavy chain (NfH‐SMI35). The statistical analyses included group comparisons, receiver operator characteristic (ROC) curves, area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values.

Results

Serum neurofilament heavy chain levels were significantly (p < 0.0001) higher in individuals with myasthenia gravis (0.19 ng/mL) than in healthy control subjects (0.07 ng/mL). A ROC AUC optimized cutoff level of 0.06 ng/mL gave a diagnostic sensitivity of 82%, specificity of 76%, positive predictive value of 0.77 and a negative predictive value of 0.81.

Discussion

The increase of serum neurofilament heavy chain levels in myasthenia gravis is consistent with observations of muscle denervation. We suggest that there is ongoing remodeling of the neuromuscular junction in myasthenia gravis. Longitudinal quantification of neurofilament isoform levels will be needed to investigate the prognostic value and potentially guide treatment decisions.
In‐line Inspection Informs Pipeline Renewal
Authors: Dsingh Parvesh , Lay Jesi
Published: May 2023

An ultrasonic tool helped a utility diagnose the condition of a metallic transmission main, target high‐risk pipe areas, and predict renewal needs.
Rebuilding a Water Treatment Plant for Operations Resilience and Climate Variability
Authors: Jensen Jeanne , Rhoades Ryan
Published: May 2023

The Southwestern community of Gilbert, Ariz., chose a proactive approach to addressing dramatic changes in its watershed and resulting treatment challenges. Comprehensive analysis showed that building a new treatment plant was the best way to go.
Spasmolytic polypeptide‐expressing metaplasia (SPEM) cell lineages can be an origin of gastric cancer
Authors: Goldenring James R
Published: May 2023

Intestinal‐type gastric cancer arises in a field of precancerous metaplastic lineages. Two types of metaplastic glands are found in the stomachs of humans with the characteristics of pyloric metaplasia or intestinal metaplasia. While spasmolytic polypeptide‐expressing metaplasia (SPEM) cell lineages have been identified in both pyloric metaplasia and incomplete intestinal metaplasia, it has been unclear whether SPEM lineages or intestinal lineages can give rise to dysplasia and cancer. A recent article published in The Journal of Pathology describes a patient with evidence of an activating Kras(G12D) mutation in SPEM that is propagated into adenomatous and cancerous lesions which manifest further oncogenic mutations. This case therefore supports the concept that SPEM lineages can serve as a direct precursor for dysplasia and intestinal‐type gastric cancer. © 2023 The Pathological Society of Great Britain and Ireland.
A review of the use of propensity score methods with multiple treatment groups in the general internal medicine literature
Authors: Shurrab Mohammed , Ko Dennis T. , Jackevicius Cynthia A. , Tu Karen , Middleton Allan , Michael Faith , Austin Peter C.
Published: May 2023

Background

Propensity score (PS) methods with two treatment groups (e.g., treated vs. control) is a well‐established technique for reducing the effects of confounding in nonrandomized studies. However, researchers are often interested in comparing multiple interventions. PS methods have been modified to incorporate multiple exposures. We described available techniques for PS methods in multicategory exposures (≥3 groups) and examined their use in the medical literature.

Methods

A comprehensive search was conducted for studies published in PubMed, Embase, Google Scholar, and Web of Science until February 27, 2023. We included studies using PS methods for multiple groups in general internal medicine research.

Results

The literature search yielded 4088 studies (2616 from PubMed, 86 from Embase, 85 from Google Scholar, 1671 from Web of Science, five from other sources). In total, 264 studies using PS method for multiple groups were identified; 61 studies were on general internal medicine topics and included. The most commonly used method was that of McCaffrey et al., which was used in 26 studies (43%), where the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) method and corresponding inverse probabilities of treatment weights were estimated via generalized boosted models. The next most commonly used method was pairwise propensity‐matched comparisons, which was used in 20 studies (33%). The method by Imbens et al. using a generalized propensity score was implemented in six studies (10%). Four studies (7%) used a conditional probability of being in a particular group given a set of observed baseline covariates where a multiple propensity score was estimated using a non‐parsimonious multinomial logistic regression model. Four studies (7%) used a technique that estimates generalized propensity scores and then creates 1:1:1 matched sets, and one study (2%) used the matching weight method.

Conclusions

Many propensity score methods for multiple groups have been adopted in the literature. The TWANG method is the most commonly used method in the general medical literature.
QSP Designer: Quantitative systems pharmacology modeling with modular biological process map notation and multiple language code generation
Authors: Matthews Richard J. , Hollinshead David , Morrison Daniel , van der Graaf Piet H. , Kierzek Andrzej M.
Published: May 2023

Typical Quantitative Systems Pharmacology (QSP) workflows involve discussion of biology, supported by graphical diagrams, followed by construction of large Ordinary Differential Equation models. QSP Designer facilitates this process by providing enhanced graphical notation, which enables hierarchical presentation with modules and handling of combinatorial complexity with diagram node arrays. Whereas the software includes a simulation engine, a major feature is full model code generation in MATLAB, R, C, and Julia to support multiple modeling communities.
Massive pulmonary embolism led to cardiac arrest two days after thoracoscopy in a young male with pleural tuberculosis
Authors: Kanjo Wael , Abbarh Shahem , Bougaila Amina , Sadik Nagham , Habib Mhd Baraa
Published: May 2023

TB itself is considered an independent risk factor for VTE; however, developing pulmonary embolism after medical thoracoscopy is extremely rare. Herein, we describe a 30‐year‐old previously healthy male with pleural tuberculosis developed a massive pulmonary embolism with subsequent cardiac arrest after a diagnostic medical thoracoscopy. Computed tomography pulmonary angiogram (CTPA) showed major right pulmonary embolism (PE). Unfortunately, the patient passed away despite resuscitation and extensive organ support in the intensive care unit (ICU). This case highlights the thrombotic risk in this population group in order to avoid such devastating complications.