bluuebunny/crossref_metadata_2025 huggingface dataset:
The breathtaking world of human respiratory in vitro models: Investigating lung diseases and infections in 3D models, organoids, and lung‐on‐chip
Authors: Dichtl Stefanie , Posch* Wilfried , Wilflingseder Doris
Published: February 2024

The COVID‐19 pandemic illustrated an urgent need for sophisticated, human tissue models to rapidly test and develop effective treatment options against this newly emerging severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Thus, in particular, the last 3 years faced an extensive boost in respiratory and pulmonary model development. Nowadays, 3D models, organoids and lung‐on‐chip, respiratory models in perfusion, or precision‐cut lung slices are used to study complex research questions in human primary cells. These models provide physiologically relevant systems for studying SARS‐CoV‐2 and, of course, other respiratory pathogens, but they are, too, suited for studying lung pathologies, such as CF, chronic obstructive pulmonary disease, or asthma, in more detail in terms of viral infection. With these models, the cornerstone has been laid for further advancing the organs by, for example, inclusion of several immune cell types or humoral immune components, combination with other organs in microfluidic organ‐on‐chip devices, standardization and harmonization of the devices for reliable and reproducible drug and vaccine testing in high throughput.
Extracellular vesicles: Messengers of allergic immune responses and novel therapeutic strategy
Authors: Möbs Christian , Jung Anna Lena
Published: February 2024

Extracellular vesicles (EVs) are nanosized particles released by nearly every cell type across all kingdoms of life. As a result, EVs are ubiquitously present in various human body fluids. Composed of a lipid bilayer, EVs encapsulate proteins, nucleic acids, and metabolites, thus playing a crucial role in immunity, for example, by enabling intercellular communication. More recently, there has been increasing evidence that EVs can also act as key regulators of allergic immune responses. Their ability to facilitate cell‐to‐cell contact and to transport a variety of different biomolecules enables active modulation of both innate and adaptive immune processes associated with allergic reactions. A comprehensive understanding of the intricate mechanisms underlying the interactions among allergens, immune cells, and EVs is imperative to develop innovative strategies for controlling allergic responses. This review highlights the recent roles of host cell‐ and bacteria‐derived EVs in allergic diseases, presenting experimental and clinical evidence that underscores their significance. Additionally, the therapeutic potential of EVs in allergy management is outlined, along with the challenges associated with targeted delivery and cargo stability for clinical use. Optimization of EV composition and targeting strategies holds promise for advancing translational applications and establishing EVs as biomarkers or safe therapeutics for assessing allergic reactions. For these reasons, EVs represent a promising avenue for advancing both our understanding and management of allergic immune processes.
Physical properties and mass models of Deglet Noor and Arichti semi‐dry Algerian date fruits: A comparative study
Authors: Roumani Messaoud , Remmani Rania , Miladi Malek , Abu‐Khalaf Nawaf , Canales Antonio Ruiz
Published: February 2024

For thousands of years, date fruit (Phoenix dactylifera L.) has been a popular diet in arid and semi‐arid locations. It has religious importance for Muslims and is especially important during the holy month of Ramadan. The global output of date fruits has been continuously expanding, with Arab nations accounting for a sizable portion. The emphasis of this research is on two popular semi‐dry Algerian date fruit types, Deglet Noor and Arechti, which are grown in the Ziban region. These fruits' physical parameters, such as size, sphericity, surface area, volumes, and density, were determined. The goal of this study was to create a mass model based on these physical attributes to help in the grading and sorting of date fruits. Fruit mass was shown to be closely connected to linear dimensions, arithmetic and geometric mean diameters, surface area, and volumes. Correlations between mass and physical attributes were established using a variety of mathematical models, including linear, quadratic, S‐curve, and power models. The results demonstrated the applicability of specific factors for mass modeling, offering useful insights for the development of system sizing and conservation. With good correlation, multivariate data analysis was employed to correctly estimate the mass of both kinds. This research advances our understanding of the physical features of Algerian date fruits and their connection to mass, allowing for better handling, sorting, and packing processes in the worldwide date market.
Aquaporin‐4 and transient receptor potential vanilloid 4 balance in early postnatal neurodevelopment
Authors: Cibelli Antonio , Mola Maria Grazia , Saracino Emanuela , Barile Barbara , Abbrescia Pasqua , Mogni Guido , Spray David C. , Scemes Eliana , Rossi Andrea , Spennato Diletta , Svelto Maria , Frigeri Antonio , Benfenati Valentina , Nicchia Grazia Paola
Published: February 2024

In the adult brain, the water channel aquaporin‐4 (AQP4) is expressed in astrocyte endfoot, in supramolecular assemblies, called “Orthogonal Arrays of Particles” (OAPs) together with the transient receptor potential vanilloid 4 (TRPV4), finely regulating the cell volume. The present study aimed at investigating the contribution of AQP4 and TRPV4 to CNS early postnatal development using WT and AQP4 KO brain and retina and neuronal stem cells (NSCs), as an in vitro model of astrocyte differentiation. Western blot analysis showed that, differently from AQP4 and the glial cell markers, TRPV4 was downregulated during CNS development and NSC differentiation. Blue native/SDS‐PAGE revealed that AQP4 progressively organized into OAPs throughout the entire differentiation process. Fluorescence quenching assay indicated that the speed of cell volume changes was time‐related to NSC differentiation and functional to their migratory ability. Calcium imaging showed that the amplitude of TRPV4 Ca2+ transient is lower, and the dynamics are changed during differentiation and suppressed in AQP4 KO NSCs. Overall, these findings suggest that early postnatal neurodevelopment is subjected to temporally modulated water and Ca2+ dynamics likely to be those sustaining the biochemical and physiological mechanisms responsible for astrocyte differentiation during brain and retinal development.
Glymphatic fluid transport is suppressed by the aquaporin‐4 inhibitor AER‐271
Authors: Giannetto Michael J. , Gomolka Ryszard S. , Gahn‐Martinez Daniel , Newbold Evan J. , Bork Peter A. R. , Chang Ethan , Gresser Michael , Thompson Trevor , Mori Yuki , Nedergaard Maiken
Published: February 2024

The glymphatic system transports cerebrospinal fluid (CSF) into the brain via arterial perivascular spaces and removes interstitial fluid from the brain along perivenous spaces and white matter tracts. This directional fluid flow supports the clearance of metabolic wastes produced by the brain. Glymphatic fluid transport is facilitated by aquaporin‐4 (AQP4) water channels, which are enriched in the astrocytic vascular endfeet comprising the outer boundary of the perivascular space. Yet, prior studies of AQP4 function have relied on genetic models, or correlated altered AQP4 expression with glymphatic flow in disease states. Herein, we sought to pharmacologically manipulate AQP4 function with the inhibitor AER‐271 to assess the contribution of AQP4 to glymphatic fluid transport in mouse brain. Administration of AER‐271 inhibited glymphatic influx as measured by CSF tracer infused into the cisterna magna and inhibited increases in the interstitial fluid volume as measured by diffusion‐weighted MRI. Furthermore, AER‐271 inhibited glymphatic efflux as assessed by an in vivo clearance assay. Importantly, AER‐271 did not affect AQP4 localization to the astrocytic endfeet, nor have any effect in AQP4 deficient mice. Since acute pharmacological inhibition of AQP4 directly decreased glymphatic flow in wild‐type but not in AQP4 deficient mice, we foresee AER‐271 as a new tool for manipulation of the glymphatic system in rodent brain.
Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus‐based position paper from an ad hoc expert panel
Authors: Mauro Francesca Romana , Tedeschi Alessandra , Varettoni Marzia , Zaja Francesco , Barosi Giovanni , Zinzani Pier Luigi
Published: February 2024

Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first‐line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.
Too costly to make a difference: An examination on the relationship between online financing and economic growth
Authors: Deng Jiapin , Liu Yanchu , Xiao Wenyue
Published: February 2024

While facilitating people's access to finance and promoting financial coverage, online financing activities involve high capital costs that suppress economic growth. Using 282 Chinese cities during 2011–2020 as the sample, we examine the relationship between online financing and economic growth. Exploiting a variety of models, we find that online financing activities do not have significant effects on economic growth. Further evidence shows that the insignificant relationship between online financing and economic growth also exists in cities with less developed formal financial systems. Our analysis based on the context where borrowers and lenders do not know each other offline implies that the technology intended to promote financial coverage, if not reducing information asymmetry and hence the cost incurred in financial transactions, does not necessarily lead to desirable economic and social outcomes.
Progress toward abortion access and quality care: Examples from across the globe
Authors: Ganatra Bela , Morris Jessica L.
Published: February 2024

Synopsis

This Supplement of national‐level case studies describes progress made in abortion access including law and policy, access to information, and supportive health systems and communities.
Perils and possibilities of health exception laws: A narrative review
Authors: Shaw Dorothy , Awoonor‐Williams Koku , Brauer Annika , Gil Laura , Morales Juana Pérez , Chavkin Wendy
Published: February 2024

Forty‐seven of the 203 countries with abortion laws detailed by the Center for Reproductive Rights have a health exception (HE) clause, inconsistent in both wording and implementation, even within countries. This narrative review sought to determine the understanding and implementation of the legally permissible HE in different countries, or states, to provide clarification and guidance for strategies that will maximize permitted access to safe abortion within the law and avoid undue delays that harm the lives and health of women and their families. A multimethod approach was used. The literature search for countries with HE laws, including physical, mental, and social health, and exceptions for threat to life, rape, incest, and fetal anomaly, returned sparse results. The review of emblematic cases that had reached regional courts on the grounds of human rights violation for failure to obtain legal abortion under the country's HE clause included some examples qualifying on multiple grounds. We interviewed 15 physician advocates from 14 countries about use of the HE in their countries. Informants from Latin America interpreted the HE to refer to physical, psychological, and social health. HE laws are common but confusing, with significant opportunities to improve access through clarification and implementation. Where multiple grounds permit ending a pregnancy, the least onerous exception for the patient is the most ethical. Examples of progress in Colombia and Ghana demonstrate successful approaches to broader HE implementation.
Biomarkers for predicting efficacy of chimeric antigen receptor T cell therapy and their detection methods
Authors: Zou Bo , Song Yanzhou , Li Ning , Fan Zhongyi , Li Jie , Peng Yuanzheng , Wei Wanshan , Zhang Yuzi , Su Yinan , Meng Xianmin , Lu Hongzhou , Zhang Xingding , Tan Xiaohua , Liao Qibin
Published: February 2024

Cancer immunotherapy has emerged as the fourth most prevalent approach to tumor treatment, alongside surgery, radiotherapy, and chemotherapy. After several decades of development, chimeric antigen receptor T (CAR‐T) cell therapy, a promising branch of adoptive T‐cell therapy, has demonstrated superior efficacy and safety in comparison to other cell therapies in the treatment of cancer. At present, CAR‐T cells are predominantly used to treat hematological malignancies, although their application in solid tumors is being readily investigated. Although numerous studies have examined the biomarkers associated with the safety of CAR‐T cell therapy, few have evaluated predictors of CAR‐T cell therapeutic efficacy. Thus, the primary objective of this review article was to provide a comprehensive overview of the factors predicting the efficacy of CAR‐T cell therapy, with a particular focus on biomarkers and their detection methods.
Efficacy of atrioventricular valve regurgitation in the first trimester for the diagnosis of atrioventricular septal defect
Authors: Yang Shuihua , Liang Mengfeng , Qin Guican , Tang Yanni , Liang Yan , Pang Yulan , Yang Zuojian
Published: February 2024

Purpose

To investigate the efficacy of atrioventricular valve regurgitation (AVVR) for predicting atrioventricular septal defect (AVSD) in the first trimester.

Methods

We performed a prospective observational study, screening for complicated congenital heart diseases and AVVR in fetuses at 11 to 13+6 weeks of gestation by advanced dynamic flow in four‐chamber view and three‐vessel‐trachea view.

Results

43 549 fetuses at 11 to 13+6 weeks of gestation were screened by echocardiography, of which 37 cases were diagnosed with AVSD, including complete AVSD (31 cases), intermediate AVSD (3 cases) and partial AVSD (1 cases), undiagnosed intermediate AVSD (2 cases), and misdiagnosed case (2 cases). AVVR was observed in 34 cases (34/37) in the first trimester, 59. 46% (22/37) nuchal translucency greater than 95th percentile, 29. 73% (11/37) absence of nasal bone, 32. 43% (12/37) ductus venosus A wave inversion, and 40. 54% (15/37) had tricuspid regurgitation. The sensitivity of common AVVR in predicting AVSD is better than other ultrasonic indexes.

Conclusions

AVVR can be used as an ultrasonic indicator to predict AVSD in the first trimester, which is beneficial to detect AVSD.
Cultural competency in dental education: developing a tool for assessment and inclusion
Authors: Lopez Naty , Shingler Kristin , Real Carmen , Nirkhiwale Arpit , Quick Karin
Published: February 2024

Purpose/objectives

This study aimed to assess the cultural competency content in selected Doctor of Dental Surgery (DDS) courses and to explore the use of an assessment tool that may be used to standardize the integration of cultural competency in the dental school curriculum.

Methods

A survey was sent to course directors to determine the inclusion of four topics related to cultural competence, the mechanisms of inclusion, and their comfort level in teaching the topics in their courses.  A scan of the same courses was conducted with the use of a tool developed from an Expert Panel's recommendations for knowledge, skills, and attitudes (KSA) to be included in curricula for teaching cultural competence.

Results

Twenty‐one course directors responded.  Fifteen reported they include social determinants of health and twelve include health inequities in their courses. Faculty reported an average of 8.67 comfort level in teaching these topics but there was less comfort level in teaching cultural humility and implicit bias.  Course directors used assignments, case studies, lectures, quizzes, and patient care (clinical courses) to include the topics. The scan of courses showed that the use of the Competencies for General Dentists in course syllabi covered the recommended knowledge, skills, and attitudes for cultural competence.

Conclusions

The rubric was suitable for assessing cultural competency content.  The Competencies for General Dentists in course syllabi will allow the integration of the recommended KSA in dental courses to teach cultural competence.  However, dental faculty may need training in the integration of KSA items in course objectives and content.
A qualitative focus group analysis: Increasing fieldwork capacity in genetic counseling training programs
Authors: Jirik Rebecca , Redlinger‐Grosse Krista , Davis Claire , Nusbaum Rachel , Reiser Catherine , Berninger Taylor
Published: February 2024

Genetic counselors are an integral part of the healthcare system; however, the number of genetic counselors in many parts of the United States is limited, impacting access to comprehensive healthcare for all patients. One solution to addressing this deficit includes modifying genetic counseling training programs to increase student enrollment. Fieldwork capacity, driven by a limited number of rotation sites and supervisors, produces a significant bottleneck to entering the profession. Other professions have reported on techniques to increase fieldwork capacity; however, the practicality of these techniques for genetic counseling training has yet to be explored. This study seeks to investigate the perspectives of key stakeholders in genetic counseling training programs on the practicality of techniques already posited in the literature from other allied health professions. Semi‐structured focus group interviews with 25 participants were conducted at the 2019 National Society of Genetic Counselors conference. Participants included program directors and supervisors from clinical, industry, and laboratory backgrounds. The focus group responses were analyzed using directed content analysis and a split coding technique, after which several themes emerged within the larger domains of rotation structures, systems infrastructure, skill‐building methods, and other novel techniques to increase fieldwork capacity. Emerging themes included the importance of finding quality student placements rather than maximizing the quantity of participatory cases; a need for transparency about the transferability of skills learned from novel experiences; scaffolding student entrustment to expand supervisor capacity; and recognizing nuances in implementation for individual programs. Overall, the results emphasize the importance of openness in communication to manage expectations for students and supervisors, who may be more hesitant to try novel rotation placements and skill‐building techniques. Genetic counseling programs may use these results to address the bottleneck of fieldwork capacity, increasing student enrollment.
Development and Validation of Interpretable Machine Learning Models for Clinically Significant Prostate Cancer Diagnosis in Patients With Lesions of PI‐RADS v2.1 Score ≥3
Authors: Ruan Mingjian , Liu Yi , Yao Kaifeng , Wang Kexin , Fan Yu , Wu Shiliang , Wang Xiaoying
Published: February 2024

Background

For patients with PI‐RADS v2.1 ≥ 3, prostate biopsy is strongly recommended. Due to the unsatisfactory positive rate of biopsy, improvements in clinically significant prostate cancer (csPCa) risk assessments are required.

Purpose

To develop and validate machine learning (ML) models based on clinical and imaging parameters for csPCa detection in patients with PI‐RADS v2.1 ≥ 3.

Study Type

Retrospective.

Subjects

One thousand eighty‐three patients with PI‐RADS v2.1 ≥ 3, randomly split into training (70%, N = 759) and validation (30%, N = 324) datasets, and 147 patients enrolled prospectively for testing.

Field Strength/Sequence

3.0 T scanners/T2‐weighted fast spin echo sequence and DWI with diffusion‐weighted single‐shot gradient echo planar imaging sequence.

Assessment

The factors evaluated for csPCa detection were age, prostate specific antigen, prostate volume, and the diameter and location of the index lesion, PI‐RADSv2.1. Five ML models for csPCa detection were developed: logistic regression (LR), extreme gradient boosting, random forest (RF), decision tree, and support vector machines. The csPCa was defined as Gleason grade ≥2.

Statistical Tests

Univariable and multivariable LR analyses to identify parameters associated with csPCa. Area under the receiver operating characteristic curve (AUC), Brier score, and DeLong test were used to assess and compare the csPCa diagnostic performance with the LR model. The significance level was defined as 0.05.

Results

The RF model exhibited the highest AUC (0.880–0.904) and lowest Brier score (0.125–0.133) among the ML models in the validation and testing cohorts, however, there was no difference when compared to the LR model (P = 0.453 and 0.548). The sensitivity and negative predictive values in the validation and testing cohorts were 93.8%–97.6% and 82.7%–95.1%, respectively, at a threshold of 0.450 (99% sensitivity of the RF model).

Data Conclusion

The RF model might help for assessing the risk of csPCa and preventing overdiagnosis and unnecessary biopsy for men with PI‐RADSv2.1 ≥ 3.

Evidence Level

3

Technical Efficacy

Stage 2
Human activities influence mule deer use of overpasses across multiple scales
Authors: Hamilton Kaela M. , Bommarito Thomas , Lewis Jesse S.
Published: February 2024

Anthropogenic linear infrastructures (ALIs), including roads, railways, and canals, provide important resources to humans, but they can affect wildlife through habitat fragmentation and reduced movement through landscapes. To mitigate these effects, overpass crossing structures (i.e., overpasses) can facilitate wildlife movement across ALIs and maintain landscape connectivity. Human activities can potentially influence spatial and temporal patterns in wildlife use of overpasses; however, little information is available about human–wildlife interactions across some types of ALIs. Using remote wildlife cameras, we evaluated human and mule deer (Odocoileus hemionus) use and interactions at 43 overpasses along the Central Arizona Project canal in Arizona, USA, during 2 seasons (warm and cool) from February 2021 to February 2022. Mule deer exhibited spatial avoidance of human activities at overpasses, although the effect varied across seasons and types of human activity. At a broad scale, the presence of recreationists at overpasses did not exclude mule deer from using overpasses to cross the canal; however, human presence reduced mule deer detection probability in the warm season. At a fine scale, mule deer decreased use of overpasses as activity associated with canal personnel (i.e., security and maintenance workers) increased in the cool season. For both seasons, mule deer exhibited greater overlap in daily activity patterns with recreationists compared to canal personnel. Further, mule deer shifted daily activity patterns to be more active earlier in the morning at sites with high amounts of recreational use compared to sites with lower recreational use. Because human activities can influence mule deer crossings at overpasses, managers might consider minimizing human activities at crossing locations to increase wildlife use and promote wildlife movement across canals and other types of ALIs.
Third vaccine boosters and anti‐S‐IgG levels: A comparison of homologous and heterologous responses and poor immunogenicity in hepatocellular carcinoma
Authors: Wang Chih‐Wen , Huang Chung‐Feng , Jang Tyng‐Yuan , Yeh Ming‐Lun , Liang Po‐Cheng , Wei Yu‐Ju , Hsu Po‐Yao , Huang Ching‐I. , Hsieh Ming‐Yen , Lin Yi‐Hung , Huang Jee‐Fu , Dai Chia‐Yen , Chuang Wan‐Long , Yu Ming‐Lung
Published: February 2024

The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID‐19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA‐1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti‐S‐IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti‐S‐IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti‐S‐IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non‐decompensation and 91.3% non‐liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non‐active HCC and 94.7% non‐HCC, p < 0.001). Receiving the MMM booster regimen (OR = 10.67, 95% CI 5.20–21.91, p < 0.001) increased the odds of having significant antibody activity compared with the AZAZBNT booster regimen. Patients with active HCC had a reduced immune response to the third COVID‐19 vaccine booster. These findings underscore the importance of booster vaccinations, especially in immunocompromised patients, with superior efficacy observed with the homologous mRNA‐1273 regimen.
Virginia effort to help physicians avoid burnout goes national
Authors: Canady Valerie A.
Published: February 2024

Addressing burnout faced by health care professionals and reducing stigma and other barriers for those seeking support without repercussions to their medical license are among the goals set by the Medical Society of Virginia. The state became the first to change laws to ensure that doctors' medical records could be protected. Plans are underway to expand the initiative nationally.
Initial‐boundary value and interface problems on the real half line for the fractional advection–diffusion‐type equation
Authors: Mariano‐Morales Jesús , Vivas‐Cruz Luis Xavier , Taneco‐Hernández Marco Antonio
Published: February 2024

We use the unified transform method (UTM) to solve initial‐boundary value problems for the fractional advection–diffusion‐type equation (FADE) on the real half line. We generalize this equation using the modified definition of the Atangana–Baleanu fractional derivative of order
in order to satisfy the initial condition. A solution methodology is proposed when the UTM is implemented in fractional differential equations with boundary conditions of Dirichlet and Robin type, in particular when using the modified definitions of fractional operators with non‐singular kernel. In addition, an interface problem is stated and solved in the adjacent domains
and
, where perfect contact continuity conditions are imposed. The exact solutions obtained include as a particular case, the diffusion and advection–diffusion equations with integer‐order derivatives. Finally, representative curves for the solution are shown by varying the fractional order.
On fixed point and its application to the spread of infectious diseases model in Mvb‐metric space
Authors: Alam Khairul Habib , Rohen Yumnam , Tomar Anita
Published: February 2024

This work aims to prove new results in an
‐metric space for a noncontinuous single‐valued self‐map. As a result, we extend, generalize, and unify various fixed‐point conclusions for a single‐valued map and come up with examples to exhibit the theoretical conclusions. Further, we solve a mathematical model of the spread of specific infectious diseases as an application of one of the conclusions. In the sequel, we explain the significance of
‐metric space because the underlying map is not necessarily continuous even at a fixed point in
‐metric space thereby adding a new answer to the question concerning continuity at a fixed point posed by Rhoades. Consequently, we may conclude that the results via
‐metric are very inspiring, and underlying contraction via
‐metric does not compel the single‐valued self‐map to be continuous even at the fixed point. Our research is greatly inspired by the exciting possibilities of using noncontinuous maps to solve real‐world nonlinear problems.
Notes on Liouville‐type theorems for the 3D compressible nematic liquid crystal equations
Authors: Zhang Jie , Wang Shu , Ji Xiang
Published: February 2024

In this note, we investigate steady compressible nematic liquid crystal flows in
. We establish Liouville‐type theorems for smooth solutions
that fulfill specific conditions within Lorentz spaces.
Existence of transonic shocks in a cylindrical nozzle with given exit normal momentums
Authors: Chen Chao , Wang Zhiyong
Published: February 2024

In this paper, we study the existence of transonic shocks in a cylindrical nozzle. More precisely, given the compatible outer normal momentum at the exit of a cylindrical nozzle, there exists a transonic shock solution such that the incoming supersonic flow is compressed to some subsonic flow. The shock position is uniquely determined by the exit normal momentum when we fix one point of the shock. This problem can be reduced to solve a nonlinear free boundary value problem for a hyperbolic–elliptic coupled system and the key ingredient is to solve a second‐order quasilinear elliptic equation with a nonlocal term by the method of separation of variables.
Higher‐order inverse mass matrices for the explicit transient analysis of heterogeneous solids
Authors: Cimrman Robert , Kolman Radek , González José A. , Park K.C.
Published: February 2024

New methods are presented for the direct computation of higher‐order inverse mass matrices (also called reciprocal mass matrices) that are used for explicit transient finite element analysis. The motivation of this work lies in the need of having appropriate sparse inverse mass matrices, which present the same structure as the consistent mass matrix, preserve the total mass, predict suitable frequency spectrum and dictate sufficiently large critical time step sizes. For an efficient evaluation of the reciprocal mass matrix, the projection matrix should be diagonal. This condition can be satisfied by adopting dual shape functions for the momentum field, generated from the same shape functions used for the displacement field. A theoretically consistent derivation of the inverse mass matrix is based on the three‐field Hamilton principle and requires the projection matrix to be evaluated from the integral of these shape functions. Unfortunately, for higher‐order FE shape functions and serendipity FE elements, the projection matrix is not positive definitive and can not be employed. Therefore, we study several lumping procedures for higher order reciprocal mass matrices considering their effect on total‐mass preserving, frequency spectra and accuracy in explicit transient simulations. The article closes with several numerical examples showing suitability of the direct inverse mass matrix in dynamics.
Catalytically Oxidizing Manganese Improves Results
Authors: Qureshi Naeem , Strand Emily , Shelton Mike , Peterson Caleb
Published: February 2024

At its recently built water treatment plant, a Minnesota water utility compared catalytically oxidizing manganese with chlorine against using sodium permanganate. The chlorine came out the winner.
New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours†
Authors: Rajpert‐De Meyts Ewa , Goriely Anne , Almstrup Kristian
Published: February 2024

Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia in situ (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of The Journal of Pathology. The emerging picture suggests the presence of two distinct trajectories for SpTs, involving either RAS/mitogen‐activated protein kinase pathway mutations or a ploidy shift with secondary TP53 mutations and/or gain of chromosome 12p, the latter known as pathognomonic for type II GCNIS‐derived TGCTs. Here, we discuss the implications of these findings, seen from the perspective of germ cell biology and the unique features of different TGCTs. The evolving phenotype of SpTs, induced by genomic and epigenetic changes, illustrates that the concept of plasticity applies to all germ cell tumours, making them inherently heterogenous and capable of significant transformation during progression. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
The evolving genetic etiology of conotruncal anomalies
Authors: Sacco Adalina , Talker Ronel , Sarkies Lyndall , Ashraf Tazeen , Chandler Natalie Jane , Pandya Pranav , Jowett Victoria , Hillman Sara
Published: February 2024

Objective

To assess the diagnostic yield of genetic testing for antenatally detected conotruncal defects.

Method

This was a retrospective analysis of all antenatally detected cases of conotruncal anomalies over a 4‐year period. Patients were offered antenatal and postnatal genetic testing including QF‐PCR, microarray and exome sequencing (ES) antenatally or genome sequencing (GS) postnatally on a case‐by‐case basis.

Results

There were 301 cases included. Overall, there were pathogenic genetic findings in 27.6% of the cases tested (53/192). The commonest finding was 22q11.21 deletion (20/192 cases, 10.4%), followed by trisomy 21 (6/192, 3.1%). There were 249 cases of isolated conotruncal anomalies, of which 59.8% (149/249) had genetic testing and 22.8% (34/149) had pathogenic findings. ES/GS was performed in five cases with no pathogenic findings. There were 52 cases of non‐isolated contruncal anomalies, of which 82.7% (43/52) had genetic testing. ES/GS was performed in 11 cases in this group and increased the yield of clinically significant diagnoses from 32.6% (14/43) to 44.2% (19/43).

Conclusion

Genetic abnormalities are present in over one quarter of cases of antenatally detected conotruncal anomalies. The commonest abnormality is 22q11.21 deletion. Exome sequencing or genome sequencing leads to a significant increase in genetic diagnosis in non‐isolated cases.
VAR2HP recognizing heparin‐like epitopes in targeted therapy and diagnosis of tumors
Authors: Xu Yingying , Liu Yi , Zou Ruyi , Yuan Xunyi , Wei Lin , Qin Yong , Wang Xu , Zhao Yunxue , Yang Zhenqiu , Wang Wenshuang , Li Fuchuan
Published: February 2024

The synthesis of glycosaminoglycans (GAGs) in vivo occurs with high spatiotemporal specificity, and any aberrant expression of GAGs is closely related to the occurrence of diseases. In terms of tumorigenesis, the abnormally expressed GAGs have become a potential target for the diagnosis and therapy of tumors. As previously reported, VAR2HP, a protein probe that recognizes the unique heparin (Hep)‐like epitopes, interacts with a decasaccharide structure containing at least three HexA2S(1‐4)GlcNS6S disaccharides. Its recognition epitopes are overexpressed in various tumor cells and appear promising as target molecules of multiple tumors. Herein, we found that VAR2HP used as an antineoplastic carrier could promote drug enrichment in tumor sites by targeting the specific Hep‐like epitopes on tumor cells, thereby reducing the damage to normal cells in vitro and in vivo. Moreover, VAR2HP acting on cells alone could inhibit cell proliferation, indicating that VAR2HP as a drug carrier has a dual effect of antitumor activity. Additionally, we observed that VAR2HP significantly stained cancer tissues more strongly than neighboring nonmalignant tissues. The staining was competitively inhibited by added exogenous Hep, indicating that the Hep‐like epitopes recognized by VAR2HP were a potential target molecule in tumor diagnosis. Moreover, the VAR2HP‐bound Hep‐like epitopes were found to be overexpressed in the sera of patients with hepatocellular carcinoma (HCC) but not in normal persons and patients with cirrhosis. Taken together, this study shows that VAR2HP and its heparin‐like epitopes have great potential in targeted therapy of tumors and HCC diagnosis.
Recent advances in design strategies of aptamer‐based liquid biopsy
Authors: Lin Bingqian , Jiang JinTing , Zhou Xiang
Published: February 2024

Liquid biopsy represents a groundbreaking technology enabling the detection, analysis, and monitoring of circulating targets in body fluids, such as blood, to acquire crucial molecular insights into tumorigenesis and progression mechanisms. Offering non‐invasiveness and real‐time capabilities, liquid biopsy facilitates the tracking of tumor evolutionary dynamics and exploration of tumor heterogeneity, thereby holding immense value for tumor diagnosis, personalized treatment, and prognostication. Therefore, an effective analysis of circulating targets in body fluids is essential. However, the complexity of biological systems poses notable challenges to achieving high sensitivity and accuracy in liquid biopsy. Aptamers possess inherent advantages of high specificity and affinity, with the added benefit of modifiability and design flexibility to enhance their performance under different practical conditions, rendering them ideal recognition elements for liquid biopsy. This review provides a comprehensive summary of design strategies for aptamer applications in liquid biopsy, including advanced aptamer screening strategies, aptamer‐based recognition designs, and signal amplification techniques. Ultimately, we present an outlook into the future prospects and directions of aptamer applications in the liquid biopsy.
Ag Surface Outflow Kinetics in Ag/AlN Nanomultilayers
Authors: Druzhinin Aleksandr V. , Janczak‐Rusch Jolanta , Cancellieri Claudia
Published: February 2024

The heat‐induced microstructure evolution of nanomultilayers (NMLs) with metallic components is widely studied due to its critical importance in ensuring the reliable application of these nanomaterials. The thermal degradation of NMLs is controlled by mass transport of one of the NML components from the NML volume to its surface. The outflow occurs at temperatures well below the melting point of metal, offering new opportunities for the engineering of innovative NML‐based brazing fillers. A combined experimental‐modeling approach for the quantitative analysis of silver (Ag) outflow kinetics in Ag/AlN NMLs is presented. The method is based on in situ monitoring of the X‐ray diffraction intensity evolution of Ag acquired from the near‐surface region of NML (grazing incidence geometry) upon annealing in the temperature range of 230–425 °C (atmosphere of N2). The experimental data are compared to model predictions of Ag diffusion. It is assumed that Ag diffusion is driven by the relaxation of residual stresses in Ag nanolayers. Due to the multilayer geometry, the surface outflow kinetics are mainly defined by the kinetics of Ag diffusion along Ag/AlN interphase boundaries. The parameters defining the Ag surface outflow kinetics, i.e., diffusion coefficients and activation energy for diffusion, are derived.
Fractionation and characterization of heat‐stable basil seed protein isolates and their utilization in high protein gluten‐free bread
Authors: Rashid Mohammad , Gülseren İbrahim
Published: February 2024

Basil (Ocimum basilicum L.) is an annual plant known for its essential oil and phenolic content. The aim of this study was to isolate and characterize proteins from basil seeds and evaluate their potential in food fortification. The mucilage was removed from the seed by aqueous extraction and thermal hydration, whereas oil was removed via cold pressing. Basil seed protein isolate (BSPI) was obtained by an alkali extraction‐isoelectric precipitation method and contained approximately 95% protein. Once BSPI was fractionated, the samples were characterized by albumin (13.5%), globulin (16.7%), glutelin (39.5%), and prolamin (30.2%) fractions. The denaturation temperature of BSPI and its fractions ranged between 93 and 142°C. Through the analysis of Fourier transform infrared spectra, β‐sheet and β‐turn elements were found to be dominant secondary structures accounting for 89.4% in BSPI, which in turn lead to enhanced thermal stability. Since aqueous dispersibility and water holding capacity (WHC) values were acceptable, BSPI was further utilized in the manufacture of gluten‐free bread. The textural parameters of bread supplemented with 2%, or 10% basil seed protein were mostly comparable to the controls rendering basil protein fortification possible in a staple food, especially for countries where basil is produced in high quantities and is reasonably affordable.
Pumping with Modified Polyurethane Sponge: An Alternative Technology for Removing Oil Spills from Water Surface
Authors: Meng Yupu , Zhu Chuanyu , Huang Zhiwei , Wu Genhua , Wang Zhuqing
Published: February 2024

We have prepared a super‐hydrophobic/super‐oleophilic modified sponge material (C‐PDMS‐PU) by attaching carbon powder and polydimethylsiloxane (PDMS) to a sponge skeleton by a simple dip‐coating method using a low‐cost polyurethane sponge as the raw material. The material has a C‐PDMS composite hydrophobic coating, which can efficiently and selectively absorb oil slicks on the water surface or organic solvents underwater that are 21–26 times its weight. Relying on this adsorbent, we have built an oil collection device that can in‐situ absorb/desorb oil with a dynamic viscosity ranging from 0 CP to 172 CP on the water surface or underwater. This oil collection device is small, simple to operate, and portable, thus freeing the adsorbent from the limits of adsorption capacity while continuously and efficiently recovering the oil from the sea surface, hence achieving the integration of adsorption and separation. This new adsorbent and the oil collection device have promising applications in emergencies, such as organic solvent spills, tanker spills, and oil spills from offshore rigs.
Design, Synthesis and Activity Evaluation Against Drug‐Resistant Bacteria of 6’‐Amidine Modified Aminoglycoside Derivatives
Authors: Xu Jianguo , Zhang Xiaomei , Xu Guoqiang , Zhang Yan , Li Hui , Shi Jinsong
Published: February 2024

The issue of bacterial resistance has become a matter of significant concern globally, prompting extensive research into the development and clinical application of aminoglycoside antibiotics (AGAs) as a crucial antibacterial therapy. One of the primary mechanisms contributing to aminoglycoside antibiotic resistance is the action of aminoglycoside modifying enzymes (AMEs), which modify aminoglycoside antibiotics and consequently confer drug resistance. Chemical modification of the AME action site can eliminate functional groups vulnerable to AMEs, thus improving drug resistance. This study involves the introduction of α‐hydroxy‐γ‐aminobutyric acid and amidine to the 1 and 6′ positions of sisomicin, respectively, to produce a range of 6′‐amidine modified sisomicin derivatives of AGAs. The research evaluates the antibacterial activity, absorption, distribution, metabolism, and excretion (ADME) properties, pharmacokinetic properties, cytotoxicity, nephrotoxicity, and drug resistance of AGAs. The outcomes of this study are significant in terms of enriching the structural understanding of aminoglycosides, providing insight into their structure–activity relationship, and producing new AGAs with high antibacterial activity, low ototoxicity, and nephrotoxicity.
Charge Puddles Driven Complex Crossover of Magnetoresistance in Non‐Topological Sulfur Doped Antimony Selenide Nanowires
Authors: Kumar Sushil , Kumar Dileep , Venkatesh R.
Published: February 2024

A race to achieve a crossover from positive to negative magnetoresistance is intense in the field of nanostructured materials to reduce the size of memory devices. Here, the unusual complex magnetoresistance in nonmagnetic sulfur‐doped Sb2Se3 nanowires is demonstrated. Intentionally, sulfur is doped in such a way to nearly achieve the charge neutrality point that is evident from switching of carrier type from p‐type to n‐type at 13 K as inferred from the low‐temperature thermoelectric power measurements. A change from 3D variable range hopping (VRH) to power law transport with α = 0.18  in resistivity measurement signifies a Luttinger liquid transport with weak links through the nanowires. Interestingly, high magnetic field induced negative magnetoresistance (NMR) occurring in hole dominated temperature regimes can only be explained by invoking the concept of charge puddles. Spot energy dispersive spectroscopy (EDS), magnetic force microscopy (MFM) measurements, Tmott and Regel plot indicate an enhanced disorder in these sulfurized nanowires that are found to be the precursor for the formation of these charge puddles. Tunability of conducting states in these nanowires is investigated in the light of interplay of carrier type, magnetic field, temperature, and intricate intra‐inter wire transport that makes this nanowires potential for large scale spintronic devices.
A drug delivery platform using engineered MUC1‐targeting exosomes enhances chemosensitivity and immunogenic cell death in pancreatic ductal adenocarcinoma
Authors: Guo Meng , Sun Chen , Liu Ruolan , Jiang Jiao , Qian Yuping , Yang Yulong , Sun Qinying , Dong Yuchao , Zhao Yan , Liu Yanfang
Published: February 2024

Exosomes, a specific subset of extracellular vesicles, have diverse functions in various biological processes. In the field of cancer research, there has been a growing interest in the potential of exosomes to act as versatile vehicles for targeted tumor imaging and therapy. In this study, we constructed a targeted delivery platform using hypoimmunogenic exosomes by genetically modifying β2‐microglobulin knocking‐out HEK‐293F cells to express a fusion protein, referred to as αMUC1‐Exo, which comprises the exosomal membrane‐enriched platelet‐derived growth factor receptor, intracellular nanoluciferase, and extracellular anti‐MUC1 single‐chain variable fragment. The findings of this study indicate that αMUC1‐Exos exhibited notable drug delivery properties toward MUC1‐positive pancreatic cancer cells, resulting in a substantial inhibition of tumor growth. Moreover, these exosomes demonstrated a high level of biosafety and the absence of any adverse effects. The application of engineered exosomes as a vehicle for drug delivery holds promise for enhancing the immunogenicity of neoplastic cells following treatment, thereby inducing antitumor immune memory in mice with intact immune systems, and also improving the response to anti‐PD1 therapy. This approach utilizing engineered exosomes for Gemcitabine administration holds promise as a potential strategy for overcoming drug resistance in pancreatic carcinoma thereby improving the overall treatment efficacy.