bluuebunny/crossref_metadata_2025 huggingface dataset:
Orlistat mouth rinse: Using the tongue to deliver antiobesity medication in a double‐blind randomized crossover pilot trial
Authors: Primeaux Stefany D. , Dubin Robert , Greenway Frank L.
Published: May 2023

Aim

To investigate the effects of an orlistat mouth rinse on the intake of a high‐fat meal.

Methods

A double‐blind, balanced order, crossover study was conducted in participants (n = 10, body mass index 25‐30 kg/m2) assigned to receive placebo or orlistat (24 mg/mL) prior to a high‐fat meal. Participants were divided into low‐ or high‐fat consumers based on calories consumed from fat following placebo administration.

Results

The orlistat mouth rinse decreased total and fat calories consumed during the high‐fat meal in high‐fat consumers, and did not alter calories consumed in low‐fat consumers (P < 0.05).

Conclusions

Orlistat decreases long‐chain fatty acid (LCFA) absorption by inhibiting lipases that breakdown triglycerides. Orlistat mouth rinse decreased fat intake in high‐fat consumers, suggesting that orlistat inhibited the detection of LCFAs from the high‐fat test meal. Lingual delivery of orlistat is predicted to eliminate the risk of oil incontinence and promote weight loss in individuals who prefer fat.
A coin of Queen Fastrada and Charlemagne
Authors: Coupland Simon
Published: May 2023

A Carolingian coin has recently been acquired by the Centre Charlemagne in Aachen which represents an entirely unexpected and truly historic addition to our knowledge of the reign of Charlemagne, as it bears the name of his wife Fastrada. It is the first known example of a queen being named on a Carolingian coin, and because the coin type was only introduced in 793 and Fastrada died in August 794, it can be very precisely dated. Charles was almost certainly prompted to strike it by learning of pennies of Cynethryth minted by Offa in the late 780s. The coinage reflects both the affection in which Charlemagne held Fastrada and the power he was prepared to share with her.
Excitatory–inhibitory mismatch shapes node recruitment in an epileptic network
Authors: Luo Peijuan , Yang Fan , Li Jing , Niemeyer James E. , Zhan Fengrui , Estin Joshua , Zhao Mingrui , Li Dan , Lin Weihong , Liou Jyun‐You , Ma Hongtao , Schwartz Theodore H.
Published: May 2023

Objective

Focal epilepsy is thought to be a network disease, in which epileptiform activity can spread noncontiguously through the brain via highly interconnected nodes, or hubs, within existing networks. Animal models confirming this hypothesis are scarce, and our understanding of how distant nodes are recruited is also lacking. Whether interictal spikes (IISs) also create and reverberate through a network is not well understood.

Methods

We injected bicuculline into the S1 barrel cortex and employed multisite local field potential and Thy‐1 and parvalbumin (PV) cell mesoscopic calcium imaging during IISs to monitor excitatory and inhibitory cells in two monosynaptically connected nodes and one disynaptically connected node: ipsilateral secondary motor area (iM2), contralateral S1 (cS1), and contralateral secondary motor area (cM2). Node participation was analyzed with spike‐triggered coactivity maps. Experiments were repeated with 4‐aminopyridine as an epileptic agent.

Results

We found that each IIS reverberated throughout the network, differentially recruiting both excitatory and inhibitory cells in all connected nodes. The strongest response was found in iM2. Paradoxically, node cM2, which was connected disynaptically to the focus, was recruited more intensely than node cS1, which was connected monosynaptically. The explanation for this effect could be found in node‐specific excitatory/inhibitory (E/I) balance, as cS1 demonstrated greater PV inhibitory cell activation compared with cM2, where Thy‐1 excitatory cells were more heavily recruited.

Significance

Our data show that IISs spread noncontiguously by exploiting fiber pathways that connect nodes in a distributed network and that E/I balance plays a critical role in node recruitment. This multinodal IIS network model can be used to investigate cell‐specific dynamics in the spatial propagation of epileptiform activity.
Cancer survival stories: Perception, creation, and potential use case
Authors: Canella Claudia , Inderbitzin Martin , Oehler Manuela , Witt Claudia M. , Barth Jürgen
Published: May 2023

Background

Cancer patients often search for information about their health conditions online. Cancer patient narratives have established themselves as a way of providing information and education but also as an effective approach to improving coping with the disease.

Objective

We investigated how people affected by cancer perceive cancer patient narratives and whether such stories can potentially improve coping during their own cancer journeys. Additionally, we reflected on whether our co‐creative citizen science approach can contribute to gaining knowledge about cancer survival stories and providing peer support.

Design, Setting and Stakeholders

We applied a co‐creative citizen science approach by using quantitative and qualitative research methods with stakeholders (i.e., cancer patients, their relatives, friends and health professionals).

Main Outcome Measures

Understandability and perceived benefits of cancer survival stories, coping, emotional reactions to the stories and helpful characteristics of the stories.

Results

Cancer survival stories were considered intelligible and beneficial, and they potentially support positive emotions and coping in people affected by cancer. Together with the stakeholders, we identified four main characteristics that evoked positive emotions and that were considered especially helpful: (1) positive attitudes towards life, (2) encouraging cancer journeys, (3) individual coping strategies for everyday challenges and (4) openly shared vulnerabilities.

Conclusions

Cancer survival stories potentially support positive emotions and coping in people affected by cancer. A citizen science approach is suitable for identifying relevant characteristics of cancer survival stories and may become a helpful educational peer support resource for people coping with cancer.

Patient or Public Contributions

We adopted a co‐creative citizen science approach, wherein citizens and researchers were equally involved throughout the entire project.
Impact of cytoreductive nephrectomy prior to combination therapy of ipilimumab plus nivolumab in metastatic renal cell carcinoma
Authors: Hara Takuto , Furukawa Junya , Shiraishi Yusuke , Okamura Yasuyoshi , Bando Yukari , Terakawa Tomoaki , Harada Kenichi , Nakano Yuzo , Fujisawa Masato
Published: May 2023

Objectives

The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real‐world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC.

Methods

Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression‐free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment.

Results

Twenty‐one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5–NR) and 3.4 months (95%CI 2.0–5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR–NR) and 12.6 months (95%CI 4.2–30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN.

Conclusions

Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.
Lights, fluorescence, action—Influencing wound treatment plans including debridement of bacteria and biofilms
Authors: Jacob Ashley , Jones Laura M. , Abdo Raymond J. , Cruz‐Schiavone Sebastian F. , Skerker Robert , Caputo Wayne J. , Krehbiel Nathan , Moyer‐Harris Audrey K. , McAtee Alyssa , Baker Isabel , Gray Micaela D. , Rennie Monique Y.
Published: May 2023

High bacterial loads within chronic wounds increase the risk of infection and complication. Detection and localization of bacterial loads through point‐of‐care fluorescence (FL) imaging can objectively inform and support bacterial treatment decisions. This single time‐point, retrospective analysis describes the treatment decisions made on 1000 chronic wounds (DFUs, VLUs, PIs, surgical wounds, burns, and others) at 211 wound‐care facilities across 36 US states. Clinical assessment findings and treatment plans derived from them, as well as subsequent FL‐imaging (MolecuLight®) findings and any associated treatment plan changes, were recorded for analysis. FL signals indicating elevated bacterial loads were observed in 701 wounds (70.8%), while only 293 (29.6%) showed signs/symptoms of infection. After FL‐imaging, treatment plans changed in 528 wounds as follows: more extensive debridement (18.7%), more extensive hygiene (17.2%), FL‐targeted debridement (17.2%), new topical therapies (10.1%), new systemic antibiotic prescriptions (9.0%), FL‐guided sampling for microbiological analysis (6.2%), and changes in dressing selection (3.2%). These real‐world findings of asymptomatic bacterial load/biofilm incidence, and of the frequent treatment plan changes post‐imaging, are in accordance with clinical trial findings using this technology. These data, from a range of wound types, facilities, and clinician skill sets, suggest that point‐of‐care FL‐imaging information improves bacterial infection management.
Evaluation of an antibacterial peptide‐loaded amniotic membrane/silk fibroin electrospun nanofiber in wound healing
Authors: Moosazadeh Moghaddam Mehrdad , Farhadie Behrouz , Mirnejad Reza , Kooshki Hamid
Published: May 2023

Antimicrobial peptides (AMPs) are among the compounds that have significant potential to deal with infectious skin wounds. Using wound dressings or skin scaffolds containing AMPs can be an effective way to overcome infections caused by antibiotic‐resistant strains. In this study, we developed an amniotic membrane‐based skin scaffold using silk fibroin to improve mechanical properties and CM11 peptide as an antimicrobial peptide. The peptide was coated on the scaffold using the soaking method. The fabricated scaffold was characterised by SEM and FTIR, and their mechanical strength, biodegradation, peptide release, and cell cytotoxicity analyses were performed. Then, their antimicrobial activity was measured against antibiotic‐resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. The in vivo biocompatibility of this scaffold was evaluated by subcutaneously implanting it under the skin of the mouse and counting lymphocytes and macrophages in the implanted area. Finally, the regenerative ability of the scaffold was analyzed in the mouse full‐thickness wound model by measuring the wound diameter, H&E staining, and examining the expression rate of genes involved in the wound healing process. The developed scaffolds exerted an inhibiting effect on the bacteria growth, indicating their proper antimicrobial property. In vivo biocompatibility results showed no significant count of macrophages and lymphocytes between the test and control groups. The wound closure rate was significantly higher in the wound covered with fibroin electrospun‐amniotic membrane loaded with 32 μg/mL CM11, where the relative expression rates of collagen I, collagen III, TGF‐β1 and TGF‐β3 were higher compared with the other groups.
CMAS corrosion behavior of a LaPO4 ceramic prepared by spark plasma sintering
Authors: Dong Hongying , Liu Lu , Wang Shaokun , Qi Yingwei , Qi Haolei , Geng Qing , Shuang Yingchai , Ma Wen
Published: May 2023

At high temperatures in gas turbines, traditional yttria stabilized zirconia materials fail prematurely owing to CMAS (calcium–magnesium–alumina–silicate) corrosion. Thus, new materials need to be developed urgently. In this study, LaPO4 powder was synthesized by chemical coprecipitation and heat treatment using lanthanum nitrate (La(NO3)3∙6H2O) and ammonium dihydrogen phosphate (NH4H2PO4) as starting materials, and LaPO4 bulk was prepared by spark plasma sintering. The surface of the LaPO4 bulk was coated with CMAS (CaO–MgO–Al2O3–SiO2) powder, and the CMAS interaction with the LaPO4 bulk at different temperatures was investigated. The phase and microstructure of the LaPO4 powder and bulk, as well as the CMAS corrosion products, were characterized using X‐ray diffraction and scanning electron microscope. The superior CMAS resistance of the LaPO4 bulk was attributed to the low wettability of LaPO4 by the CMAS melt and the development of dense layers of new corrosion products, which effectively protected the LaPO4 bulk from CMAS infiltration.
Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network
Authors: Xu Yangyang , Zhang Jie , Gao Fei , Cheng Wenna , Zhang Ye , Wei Chuanmei , Zhang Shuping , Gao Xinfu
Published: May 2023

High‐mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti‐inflammatory activity. Herein, we examined the mechanism of engeletin‐mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose‐dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL‐1β, TNF‐α, IL‐6 and IFN‐γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl‐2 protein levels, while suppressing Bax and Cleaved Caspase‐3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF‐κB and attenuated nuclear transfer of nuclear factor kappa B (NF‐κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF‐κB inflammatory network.
Effect of variable temperature levels on drying characteristics and quality indices of rice in continuous drying and multi‐stage intermittent drying
Authors: Wang Hongchao , Che Gang , Wan Lin , Chen Zhengfa , Sun Wensheng , Tang Hao
Published: May 2023

The aim of this study was to investigate the effect of variable temperature levels on the drying characteristics and quality indices of rice in continuous drying and multi‐stage intermittent drying (MID). The quality indices of rice were assessed in terms of stress crack index, head rice yield (HRY), color, sensory characteristics, and taste value. Moreover, the microstructure of the cross‐section of rice was analyzed at different variable temperature levels. In addition, the quality indices evaluation of rice was carried out by principal component analysis. The results showed that drying temperature at the same temperature level was positively correlated with stress cracking index and total color difference, negatively correlated with drying time, HRY, whiteness index, and taste value. The MID with Δ5 (45–50°C) temperature level had the highest comprehensive score of 1.431. The results provide a reference for optimizing the drying process for rice.

Practical applications

Drying is a key control step in relation to the yield and quality of rice. A reasonable and effective variable temperature drying process can improve drying efficiency and solve the problem of the limitations of a single temperature heating method. The quality indices evaluation of rice can provide a reference for the optimization of drying parameters for different variable temperature drying processes. Moreover, the variable temperature drying method in this study can improve the adaptability of the process and provide research ideas and technical references for the industrial production and automatic control of variable temperature in rice.
Wealth, Portfolios, and Nonemployment Duration
Authors: FONTAINE FRANÇOIS , JENSEN JANNE NYBORG , VEJLIN RUNE
Published: May 2023

We use administrative data on individual balance sheets in Denmark to document how an individual's financial position affects job search behavior. We look at the effect of wealth at the entry into unemployment on the exit rate from unemployment as well as the effect on the subsequent match quality. The detailed data allow us not only to distinguish between liquid and illiquid parts, but also to decompose each of them into assets and liabilities. The decomposition of wealth into these four components is key to understanding how wealth affects job finding rates. In particular, we show that liquid assets reduce the probability of becoming reemployed, but we do not see an effect of liquid liabilities or the illiquid wealth components, while interest payments speed up reemployment. The results on subsequent match quality in form of job duration and wages are mixed.
Provider cultural competence and humility in healthcare interactions with transgender and nonbinary young adults
Authors: Reeves Karli , Job Sarah , Blackwell Christopher , Sanchez Kyle , Carter Shannon , Taliaferro Lindsay
Published: May 2023

Purpose

Transgender and nonbinary (TGNB) patients experience many barriers when seeking quality healthcare services, including ineffective communication and negative relationships with their providers as well as a lack of provider competence (including knowledge, training, and experience) and humility (engagement in the process of self‐reflection and self‐critique) in treating TGNB individuals. The purpose of this qualitative study was to identify factors associated with cultural competence and humility that facilitate and impede effective relationships between TGNB young adults and their healthcare providers.

Methods

Data came from individual interviews with 60 young adults aged 18 to 24 from Florida who self‐identified as transgender or nonbinary. We analyzed the data using inductive thematic approaches, and a feminist perspective, to identify themes associated with patient‐provider relationships.

Conclusions

We identified 4 themes related to patient‐provider relationships: (1) Participants indicated effective patient‐provider communication and relationships are facilitated by providers requesting and utilizing TGNB patients' correct names and personal pronouns. (2) Participant narratives conveyed their preferences that providers “follow their lead” in terms of how they described their own anatomy, reinforcing the utility of cultural humility as an approach for interactions with TGNB patients (3) Participants discussed the detrimental effects of TGNB patients having to educate their own providers about their identities and needs, suggesting clinicians' competence regarding gender diversity is paramount to fostering and maintaining patient comfort. (4) Finally, participants' responses indicated concerns regarding the confidentiality and privacy of the information they provided to their providers, suggesting a lack of trust detrimental to the process of building rapport between patients and their providers.

Clinical Relevance

Our findings indicate balancing the use of cultural humility and cultural competence during clinical encounters with TGNB young adults can enhance patients' experiences seeking healthcare. Nursing education is often devoid of focus on caring for transgender and nonbinary persons. Additional provider training and education on approaching clinical encounters with TGNB patients with cultural humility and competence should improve patient‐provider communication and relationships, leading to a higher quality of patient care.
Long‐term evaluation of the upper airway following mandibular setback surgery in the patients with mandibular prognathism
Authors: Lee Kyungmin Clara
Published: May 2023

Objective

The aim of this study was to evaluate the changes in the upper airway following mandibular setback surgery.

Methods

The patients underwent mandibular setback surgery and cone‐beam computed tomography scan data obtained at four time points: before surgery, immediately after surgery, short‐ and long‐term follow‐up. Upper airway geometries were segmented and extracted at each time point. Time‐averaged airflow through the upper airway was evaluated at each time point. The measurements of airway volume and minimum cross‐sectional areas were obtained at four time points.

Results

The airway volume and cross‐sectional areas of airway significantly decreased immediately after surgery (p = 0.013 for airway volume and 0.016 for cross‐sectional area). At short‐term follow‐up, the decreased airway volume and cross‐sectional areas still showed statistically significant difference to original dimension (p = 0.017 for airway volume and 0.006 for cross‐sectional area). At long‐term follow‐up, although there were no statistical significances (p = 0.859 for airway volume and 0.721 for cross‐sectional area), the airway volume and cross‐sectional areas had increased slightly compared to those at short‐term follow‐up.

Conclusions

Although the airflow and dimensional parameters of the upper airway worsened following mandibular setback surgery, there was a tendency to gradually recover during long‐term follow‐up.
Mandibular condylar hyperplasia and its correlation with vascular endothelial growth factor
Authors: Almeida Luis Eduardo , Cicciù Marco , Doetzer Andrea , Beck Matthew L. , Cervino Gabriele , Minervini Giuseppe
Published: May 2023

Background

Condylar hyperplasia (CH) is a rare condition characterised by excessive unilateral growth of the mandibular condyle after cessation of growth on the contralateral side causing facial asymmetry, being more prevalent in the second and third decades.

Objective

The aim of this study was to determine the utility of vascular endothelial growth factor (VEGF‐A) as a diagnostic and prognostic factor in condylar hyperplasia, and to determine its potential viability as a therapeutic target.

Methods

This is a case–control study, where 17 mandibular condyles specimens were collected from 17 patients treated for active mandibular condyle hyperplasia and three unaffected human mandibular condyles from cadavers will serve as the control group. The samples were immunostained with VEGF‐A antibody and evaluated on both quantity and intensity of staining.

Results

VEGF‐A was qualitatively found to be greatly upregulated in patients with condylar hyperplasia.

Conclusion

VEGF‐A was qualitatively found to be upregulated in patients affected by CH, validating VEGF‐A as a potential diagnostic, prognostic and therapeutic target.
Oculosystemic pneumocystosis in 2 sibling Chihuahuas
Authors: Johnson Lynelle R. , Hulsebosch Sean E. , Viall Austin K. , Danesi Patrizia , Woolard Kevin D. , Cook Sarah E. , Maggs David J. , Leonard Brian C.
Published: May 2023

Sibling female and male Chihuahuas were evaluated for a 9‐month history of tachypnea that failed to respond to fenbendazole, doxycycline, amoxicillin‐clavulanate, and prednisone. Physical examination identified tachypnea, hyperpnea, and harsh bronchovesicular lung sounds. Fundic examination disclosed diffuse chorioretinitis, manifested as multifocal chorioretinal granulomas in the female dog and occasional chorioretinal scars in the male dog. Thoracic radiographs indicated moderate to severe interstitial to broncho‐interstitial infiltrates in both dogs. Serum and urine antigen and antibody testing in the female dog failed to identify infectious agents, but cytologic assessment of hepatic lymph node, liver, and splenic aspirates identified Pneumocystis trophozoites. Infection was confirmed in both dogs by 28S rRNA PCR sequencing from multiple tissue samples. The female dog responded well to trimethoprim‐sulfamethoxazole, but the male dog was euthanized because of liver failure, presumably related to antimicrobial treatment.
A paradox for tiny probabilities and enormous values
Authors: Beckstead Nick , Thomas Teruji
Published: May 2023

We begin by showing that every theory of the value of uncertain prospects must have one of three unpalatable properties. Reckless theories recommend giving up a sure thing, no matter how good, for an arbitrarily tiny chance of enormous gain; timid theories permit passing up an arbitrarily large potential gain to prevent a tiny increase in risk; non‐transitive theories deny the principle that, if is better than and is better than , then must be better than . Having set up this trilemma, we study its horns. Non‐transitivity has been much discussed; we focus on drawing out the costs and benefits of recklessness and timidity when it comes to axiology, decision theory, and normative uncertainty.
The experiences of nurses during the COVID‐19 crisis in India and the role of the state: A qualitative analysis
Authors: Mahapatro Meerambika , Prasad Moksh M.
Published: May 2023

Objectives

The study documents the lived experience of nurses coping with the double burden of external demands and internal stressors while providing care during the COVID‐19 pandemic in India.

Methods

This qualitative study interviewed 18 female nurses who worked in the COVID wards of a major hospital in India. The one‐on‐one telephonic interviews were conducted with respondents based on three broad open‐ended questions. Thematic analysis was conducted.

Results

Three themes were identified: (i) external demands such as availability, utilization, and management of resources; (ii) internal psychological stressors, such as emotional exhaustion, moral anguish, and social isolation; and (iii) promotive factors such as the roles of the state and society, and of patients and attendants

Conclusions

Findings suggest that despite limited resources and facilities, nurses ploughed through the pandemic with their resilience and the state's and society's promotive factors. To improve health care delivery in this crisis, the role of the state and healthcare system has become important to prevent the workforce from crumbling. The sustained attention of the state and society is required to reinstate motivation among nurses by raising the collective value of their contribution and capability.
Immune defences of the mammary gland in dairy ruminants
Authors: Germon Pierre , Martins Rodrigo Prado
Published: May 2023

The mammary gland (MG) of ruminants is essential for assuring the immune protection and nutrition of the suckling youngs. The domestication of these species aimed at increasing milk production for human consumption enhanced udder susceptibility to infections and in this context, a better understanding of the MG immune defences has become a cornerstone for the success of dairy farming. In this review, we explore constitutive and inducible immune mechanisms of the mammary gland and briefly discuss the knowledge gaps that remain to be elucidated for the implementation of strategies focused on boosting mammary immune responses.
A modeling approach for mean fluorescence intensity value harmonization and cutoff prediction for luminex single antigen bead assays of two different vendors
Authors: Karahan Gonca E. , Haasnoot Geert W. , Voogt‐Bakker Kim , Claas Frans H. J. , Roelen Dave , Heidt Sebastiaan
Published: May 2023

Luminex single antigen bead (SAB) kits from One Lambda (OL) and Lifecodes (LC) are widely used for HLA antibody detection but have substantial differences in design and assay protocol resulting in different mean fluorescence intensity (MFI) values. Here, we present a non‐linear modeling approach to accurately convert MFI values between two vendors and to establish user‐independent MFI cutoffs when analyzing big datasets. HLA antibody data from a total of 47 EDTA‐treated sera tested using both OL and LC SAB kits were analyzed. MFI comparisons were made for the common 84 HLA class I and 63 class II beads. In the exploration set (n = 24), a non‐linear hyperbola model on raw MFI corrected by locus‐specific highest self MFI subtraction yielded the highest correlation (class I r2: 0.946, class II r2: 0.898). Performance of the model was verified in an independent validation set (n = 12) (class I r2: 0.952, class II r2: 0.911). Furthermore, in an independent cohort of post‐transplant serum samples (n = 11) using the vendor‐specific MFI cutoffs dictated by the current model, we found 94% accuracy in bead‐specific reactivity assignments by the two vendors. We recommend using the non‐linear hyperbola modeling approach with self HLA correction and locus‐specific analyzes to harmonize MFI values between two vendors in particular research datasets. As there are considerable variations between the two assays, using MFI conversion for individual patient samples is not recommended.
Cholangiopancreatography in cats: a post‐mortem comparison of MRI with fluoroscopy, corrosion casting and histopathology
Authors: Rahmani Vahideh , Peltonen Juha , Amarilla Shyrley Paola , Spillmann Thomas , Ruohoniemi Mirja
Published: May 2023

In human medicine, magnetic resonance cholangiopancreatography (MRCP) is a valuable diagnostic tool for hepatobiliary and pancreatic diseases. In veterinary medicine, however, data evaluating the diagnostic value of MRCP are limited. The primary objectives of this prospective, observational, analytical investigation were to assess whether MRCP reliably visualizes the biliary tract and pancreatic ducts in cats without and with related disorders, and whether MRCP images and measurements of the ducts agree with those of fluoroscopic retrograde cholangiopancreatography (FRCP), corrosion casting and histopathology. A secondary objective was to provide MRCP reference diameters for bile ducts, GB, and pancreatic ducts. Donated bodies of 12 euthanized adult cats underwent MRCP, FRCP, and autopsy with corrosion casting of the biliary tract and pancreatic ducts using vinyl polysiloxane. Diameters of the biliary ducts, gallbladder (GB), and pancreatic ducts were measured using MRCP, FRCP, corrosion casts and histopathologic slides. There was an agreement between MRCP and FRCP in measuring diameters of the GB body, GB neck, cystic duct, and common bile duct (CBD) at papilla. Strong positive correlations existed between MRCP and corrosion casting for measuring GB body and neck, cystic duct, and CBD at the extrahepatic ducts’ junction. In contrast to the reference methods, post‐mortem MRCP did not visualize right and left extrahepatic ducts, and pancreatic ducts in most cats. Based on this study, MRCP with 1.5 Tesla can be regarded as a contributory method to improve the assessment of feline biliary tract and pancreatic ducts when their diameter is >1 mm.
Bringing Weight to the Weightless
Authors: Zeldovich Lina
Published: May 2023

With the planned decommissioning of the International Space Station scheduled for later this decade, there is a rush of companies drawing up plans for commercial space stations to replace it. One company is developing a station that would spin to provide weight for occupants.
Charting a New Course
Authors: Palmer Nichole M. , Thilmany Jean
Published: May 2023

We’ve selected a few examples of career-focused articles produced for ASME.org and ASME’s Career Center, which offer a wide selection of resources for engineers as they navigate the ebb and flow of work and careers.
Multi-Objective Optimal Design of a Cable-Driven Parallel Robot Based on an Adaptive Adjustment Inertia Weight Particle Swarm Optimization Algorithm
Authors: Zhou Bin , Li Sipan , Zi Bin , Chen Bing , Zhu Weidong
Published: May 2023

Cable-driven parallel robots (CDPRs) have been widely used in engineering fields because of their significant advantages including high load-bearing capacity, large workspace, and low inertia. However, the impact of convergence speed and solution accuracy of optimization approaches on optimal performances can become a key issue when it comes to the optimal design of CDPR applied to large storage space. An adaptive adjustment inertia weight particle swarm optimization (AAIWPSO) algorithm is proposed for the multi-objective optimal design of CDPR. The kinematic and static models of CDPR are established based on the principle of virtual work. Subsequently, two performance indices including workspace and dexterity are derived. A multi-objective optimization model is established based on performance indices. The AAIWPSO algorithm introduces an adaptive adjustment inertia weight to improve the convergence efficiency and accuracy of traditional particle swarm optimization (PSO) algorithm. Numerical examples demonstrate that final convergence values of the objective function by the AAIWPSO algorithm can almost be 14∼20% and 19∼40% higher than those by the PSO algorithm and genetic algorithm (GA) for the optimal design of CDPR with different configurations and masses of end-effectors, respectively.
Study on Numerical Simulation Method of Fracture Behavior of Pipeline Girth Weld
Authors: Qingshan Feng , Qun Chang , Haidong Jia , Yi Wu , Lianshuang Dai , Yuguang Cao
Published: May 2023

The failure accidents in girth weld of pipelines occur frequently due to the combination of internal defects and external loads. However, the research on the fracture behavior of girth weld defects is relatively poor at present. To solve this problem, the cracking behavior and strain evolution law of the inner wall defects of the pipe girth weld are studied in combination with full-scale tests (FST). The constitutive and Gurson-Tvergaard-Needleman damage parameters of the pipe base metal zone, weld zone and heat-affected zone (HAZ) are calibrated through the small punch test (SPT) and single edge notch bending (SENB) test. On this basis, the welded pipe model with inner wall defects is established, and a numerical simulation method for dynamic fracture behavior based on damage mechanics is formed. The numerical simulation method is verified by FST data and theoretical calculation. The results show that the numerical results are consistent with the FST and theoretical calculation in the elastic stage, plastic stage, and fracture stage, and the error is within 10%. The novel numerical simulation method is provided as a means for the fracture behavior research of pipeline girth weld.
The one-dimensional potential energy function that is analogous to a two-dimensional track
Authors: Timberlake Todd K. , Mbenoun Mahend Robert Valentin
Published: May 2023

When learning about potential energy functions, students are sometimes told that the potential energy function is analogous to that of a particle sliding along a frictionless roller coaster track or wire confined to a vertical plane with peaks and valleys of the track corresponding to unstable and stable equilibrium points. However, motion along a track with height z(x) is a constrained two-dimensional motion, not a one-dimensional motion, so the exact nature of this analogy may be unclear. We show that the horizontal motion of a point mass sliding along a frictionless track z(x) and subject to a uniform gravitational field is equivalent to the motion of a particle in one dimension characterized by an “analogous potential energy” function UE(x), which generally depends on the total energy of the system (and thus on the initial conditions). We derive a general expression for UE(x) in terms of z(x) and the total energy and show that the equilibrium points of the actual potential energy U(x)=mgz(x) are also static equilibrium points for UE(x) with the same stability. However, UE(x) may have additional dynamic equilibrium points that are not present for U(x). As an example, we derive UE(x) for a double well track and determine the period of oscillations on that track. The results show that in general a single track corresponds to many different analogous potential energy functions, each with a different value for the total energy.
Progress made in the efficacy and viability of deep-learning-based noise reduction
Authors: Healy Eric W. , Johnson Eric M. , Pandey Ashutosh , Wang DeLiang
Published: May 2023

Recent years have brought considerable advances to our ability to increase intelligibility through deep-learning-based noise reduction, especially for hearing-impaired (HI) listeners. In this study, intelligibility improvements resulting from a current algorithm are assessed. These benefits are compared to those resulting from the initial demonstration of deep-learning-based noise reduction for HI listeners ten years ago in Healy, Yoho, Wang, and Wang [(2013). J. Acoust. Soc. Am. 134, 3029–3038]. The stimuli and procedures were broadly similar across studies. However, whereas the initial study involved highly matched training and test conditions, as well as non-causal operation, preventing its ability to operate in the real world, the current attentive recurrent network employed different noise types, talkers, and speech corpora for training versus test, as required for generalization, and it was fully causal, as required for real-time operation. Significant intelligibility benefit was observed in every condition, which averaged 51% points across conditions for HI listeners. Further, benefit was comparable to that obtained in the initial demonstration, despite the considerable additional demands placed on the current algorithm. The retention of large benefit despite the systematic removal of various constraints as required for real-world operation reflects the substantial advances made to deep-learning-based noise reduction.
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis
Authors: Izzo Luke T. , Trefely Sophie , Demetriadou Christina , Drummond Jack M. , Mizukami Takuya , Kuprasertkul Nina , Farria Aimee T. , Nguyen Phuong T. T. , Murali Nivitha , Reich Lauren , Kantner Daniel S. , Shaffer Joshua , Affronti Hayley , Carrer Alessandro , Andrews Andrew , Capell Brian C. , Snyder Nathaniel W. , Wellen Kathryn E.
Published: May 2023

The metabolite acetyl-CoA is necessary for both lipid synthesis in the cytosol and histone acetylation in the nucleus. The two canonical precursors to acetyl-CoA in the nuclear-cytoplasmic compartment are citrate and acetate, which are processed to acetyl-CoA by ATP-citrate lyase (ACLY) and acyl-CoA synthetase short-chain 2 (ACSS2), respectively. It is unclear whether other substantial routes to nuclear-cytosolic acetyl-CoA exist. To investigate this, we generated cancer cell lines lacking both ACLY and ACSS2 [double knockout (DKO) cells]. Using stable isotope tracing, we show that both glucose and fatty acids contribute to acetyl-CoA pools and histone acetylation in DKO cells and that acetylcarnitine shuttling can transfer two-carbon units from mitochondria to cytosol. Further, in the absence of ACLY, glucose can feed fatty acid synthesis in a carnitine responsive and carnitine acetyltransferase (CrAT)-dependent manner. The data define acetylcarnitine as an ACLY- and ACSS2-independent precursor to nuclear-cytosolic acetyl-CoA that can support acetylation, fatty acid synthesis, and cell growth.
176
Lu
+
clock comparison at the 10
−18
level via correlation spectroscopy
Authors: Zhiqiang Zhang , Arnold Kyle J. , Kaewuam Rattakorn , Barrett Murray D.
Published: May 2023

The extreme precision of optical atomic clocks has led to an anticipated redefinition of the second by the International System of Units. Furthermore, accuracies pushing the boundary of 1 part in 10
18
and beyond will enable new applications, such as in geodesy and tests of fundamental physics. The
1
S
0
to
3
D
1
optical transition in
176
Lu
+
has exceptionally low sensitivity to external perturbations, making it suitable for practical clock implementations with inaccuracy at or below 10
−18
. Here, we perform high-accuracy comparisons between two
176
Lu
+
references using correlation spectroscopy. A comparison at different magnetic fields is used to obtain a quadratic Zeeman coefficient of −4.89264(88) Hz/mT for the reference frequency. With a subsequent comparison at low field, we demonstrate agreement at the low 10
−18
level, statistically limited by the averaging time of 42 hours. The evaluated uncertainty in the frequency difference is 9 × 10
−19
and the lowest reported in comparing independent optical references.
Therapeutic blocking of VEGF binding to neuropilin-2 diminishes PD-L1 expression to activate antitumor immunity in prostate cancer
Authors: Wang Mengdie , Wisniewski Christi A. , Xiong Choua , Chhoy Peter , Goel Hira Lal , Kumar Ayush , Zhu Lihua Julie , Li Rui , St. Louis Pamela A. , Ferreira Lindsay M. , Pakula Hubert , Xu Zhiwen , Loda Massimo , Jiang Zhong , Brehm Michael A. , Mercurio Arthur M.
Published: May 2023

Prostate cancers are largely unresponsive to immune checkpoint inhibitors (ICIs), and there is strong evidence that programmed death-ligand 1 (PD-L1) expression itself must be inhibited to activate antitumor immunity. Here, we report that neuropilin-2 (NRP2), which functions as a vascular endothelial growth factor (VEGF) receptor on tumor cells, is an attractive target to activate antitumor immunity in prostate cancer because VEGF-NRP2 signaling sustains PD-L1 expression.
NRP2
depletion increased T cell activation in vitro. In a syngeneic model of prostate cancer that is resistant to ICI, inhibition of the binding of VEGF to NRP2 using a mouse-specific anti-NRP2 monoclonal antibody (mAb) resulted in necrosis and tumor regression compared with both an anti–PD-L1 mAb and control immunoglobulin G. This therapy also decreased tumor PD-L1 expression and increased immune cell infiltration. We observed that the
NRP2
,
VEGFA
, and
VEGFC
genes are amplified in metastatic castration-resistant and neuroendocrine prostate cancer. We also found that individuals with NRP2
High
PD-L1
High
metastatic tumors had lower androgen receptor expression and higher neuroendocrine prostate cancer scores than other individuals with prostate cancer. In organoids derived from patients with neuroendocrine prostate cancer, therapeutic inhibition of VEGF binding to NRP2 using a high-affinity humanized mAb suitable for clinical use also diminished PD-L1 expression and caused a substantial increase in immune-mediated tumor cell killing, consistent with the animal studies. These findings provide justification for the initiation of clinical trials using this function-blocking NRP2 mAb in prostate cancer, especially for patients with aggressive disease.
Pathophysiology of Dyt1-
Tor1a
dystonia in mice is mediated by spinal neural circuit dysfunction
Authors: Pocratsky Amanda M. , Nascimento Filipe , Özyurt M. Görkem , White Ian J. , Sullivan Roisin , O’Callaghan Benjamin J. , Smith Calvin C. , Surana Sunaina , Beato Marco , Brownstone Robert M.
Published: May 2023

Dystonia, a neurological disorder defined by abnormal postures and disorganized movements, is considered to be a neural circuit disorder with dysfunction arising within and between multiple brain regions. Given that spinal neural circuits constitute the final pathway for motor control, we sought to determine their contribution to this movement disorder. Focusing on the most common inherited form of dystonia in humans, DYT1-
TOR1A
, we generated a conditional knockout of the torsin family 1 member A (
Tor1a
) gene in the mouse spinal cord and dorsal root ganglia (DRG). We found that these mice recapitulated the phenotype of the human condition, developing early-onset generalized torsional dystonia. Motor signs emerged early in the mouse hindlimbs before spreading caudo-rostrally to affect the pelvis, trunk, and forelimbs throughout postnatal maturation. Physiologically, these mice bore the hallmark features of dystonia, including spontaneous contractions at rest and excessive and disorganized contractions, including cocontractions of antagonist muscle groups, during voluntary movements. Spontaneous activity, disorganized motor output, and impaired monosynaptic reflexes, all signs of human dystonia, were recorded from isolated mouse spinal cords from these conditional knockout mice. All components of the monosynaptic reflex arc were affected, including motor neurons. Given that confining the
Tor1a
conditional knockout to DRG did not lead to early-onset dystonia, we conclude that the pathophysiological substrate of this mouse model of dystonia lies in spinal neural circuits. Together, these data provide new insights into our current understanding of dystonia pathophysiology.
Predicting Optimal Antimalarial Drug Combinations from a Standardized Plasmodium falciparum Humanized Mouse Model
Authors: Demarta-Gatsi Claudia , Andenmatten Nicole , Jiménez-Díaz María-Belén , Gobeau Nathalie , Cherkaoui-Rabti Mohammed H. , Fuchs Aline , Díaz Pablo , Berja Sandra , Sánchez Rebeca , Gómez Hazel , Ruiz Estíbaliz , Sainz Paula , Salazar Eider , Gil-Merino Rodrigo , Mendoza Luis Manuel , Eguizabal Cristina , Leroy Didier , Moehrle Joerg J. , Tornesi Belen , Angulo-Barturen Iñigo
Published: May 2023

The development of new combinations of antimalarial drugs is urgently needed to prevent the spread of parasites resistant to drugs in clinical use and contribute to the control and eradication of malaria. In this work, we evaluated a standardized humanized mouse model of erythrocyte asexual stages of
Plasmodium falciparum
(PfalcHuMouse) for the selection of optimal drug combinations.
Developing Scientific Communication Skills Using Primary Literature in an Undergraduate Cell Biology Course
Authors: Laslo Mara , Hartmann Michaelyn
Published: May 2023

Being able to communicate scientifically is an important skill for students graduating with a science degree. Skills used in future graduate school and careers for science majors include oral and written communication, as well as science literacy and being able to create figures to display information.
Mass wasting records the first stages of the Messinian Salinity Crisis in the eastern Mediterranean
Authors: Oppo Davide , Jackson Christopher A.-L. , Gorini Christian , Iacopini David , Evans Sian , Maselli Vittorio
Published: May 2023

The geological processes that occurred during the deposition of the Mediterranean salt giant are poorly constrained, limiting our understanding of the earliest phase of the Messinian Salinity Crisis (MSC). Using three-dimensional seismic reflection data from the northern Levant Basin in the eastern Mediterranean Sea, we investigated a previously unrecognized deposit at the base of the Messinian halite that we interpret as an extensive mass-transport complex (MTC). While MTCs have been described within stratigraphically equivalent deposits in the western Mediterranean Sea, this is the first such MTC documented at the base of the halite in the eastern Mediterranean. The spatial distribution and seismic facies of the MTC suggest a slope failure origin, likely in response to multiple processes including tectonic activity and sea-level fall. Our study indicates that margin instability was diffuse across the entire Mediterranean during the early stages of Messinian halite deposition, with implications for the chronology of erosional events and sediment transport to the deep basin.
Supplemental Material: Cd isotopic constraints on the sources of Zn-Sb deposits: A case study of the Jianzhupo Zn-Sb deposit, Guangxi Province, China
Authors: Yang Zhen , Zhu Chuanwei , al. et
Published: May 2023

Table S1: EPMA trace-element contents of jamesonite (Jam) and sphalerite (Sp) from the Jianzhupo deposit. Figure S1: General paragenetic sequence of minerals in the Jianzhupo deposit. Figure S2: Backscattered electron images (A to J) and photomicrographs (K to L; under reflected light) of sulphides from the Jianzhupo deposit. Table S2: LA-ICP-MS data (in ppm) obtained for sulfides from the Jianzhupo deposit. Table S3: End-members compositions and mixing modeling on Zn, Cd, and δ114/110Cd values.