bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐life experience of venetoclax and hypomethylating agents in acute myeloid leukemia patients not candidates for intensive chemotherapy or who are refractory/relapsed: A single‐centre experience
Authors: Roldán Pérez Alicia , Vázquez Paganini Juan Andrés , Penalva Moreno M. José , Giménez Mesa Eugenio , Vilches Moreno Alba Sara , Nuñez‐Torrón Stock Claudia , Herráez García Regina
Published: July 2022

We report our experience with venetoclax/hypomethylating agents (Ven/HMA) in 8 AML patients not candidates for intensive CT or refractory/relapsed with limited treatment options. The response rate was 50%. Venetoclax was well‐tolerated in 62.5% of the patients. Ven/HMA provides a benefit particularly when used in patients without prior HMA exposure.
A case of unresectable combined hepatocellular and cholangiocarcinoma treated with atezolizumab plus bevacizumab
Authors: Saito Naoto , Hatanaka Takeshi , Nakano Sachi , Hazama Yoichi , Yoshida Sachiko , Hachisu Yoko , Tanaka Yoshiki , Yoshinaga Teruo , Kashiwabara Kenji , Kubo Norio , Hosouchi Yasuo , Tojima Hiroki , Kakizaki Satoru , Uraoka Toshio
Published: July 2022

An 81‐year‐old man initially underwent right hepatic lobectomy for liver cancer and was pathologically diagnosed with combined hepatocellular and cholangiocarcinoma (CHC). At 13 months after resection, multiple lymph node metastases were observed. We started atezolizumab plus bevacizumab (Atez/Bev), achieving a 7.5‐month progression‐free survival. Atez/Bev might exhibit efficacy for CHC patients.
Enhanced Optical Properties of Azaborole Helicenes by Lateral and Helical Extension
Authors: Full Felix , Wölflick Quentin , Radacki Krzysztof , Braunschweig Holger , Nowak‐Król Agnieszka
Published: July 2022

The synthesis and characterization of laterally extended azabora[5]‐, ‐[6]‐ and ‐[7]helicenes, assembled from N‐heteroaromatic and dibenzo[g,p]chrysene building blocks is described. Formally, the π‐conjugated systems of the pristine azaborole helicenes were enlarged with a phenanthrene unit leading to compounds with large Stokes shifts, significantly enhanced luminescence quantum yields (Φ) and dissymmetry factors (glum). The beneficial effect on optical properties was also observed for helical elongation. The combined contributions of lateral and helical extensions resulted in a compound showing green emission with Φ of 0.31 and |glum| of 2.2×10−3, highest within the series of π‐extended azaborahelicenes and superior to emission intensity and chiroptical response of its non‐extended congener. This study shows that helical and lateral extensions of π‐conjugated systems are viable strategies to improve features of azaborole helicenes. In addition, single crystal X‐ray analysis of configurationally stable [6]‐ and ‐[7]helicenes was used to provide insight into their packing arrangements.
Ki‐67 index assessment on FNA specimens of gastrointestinal stromal tumor: Correlation with mitotic rate and potential predictive value for risk stratification
Authors: Wang Xi , Abi‐Raad Rita , Tang Haiming , Cai Guoping
Published: July 2022

Background

Risk assessment of gastrointestinal stromal tumor (GIST) is challenging on cytology specimens. This study aims to determine whether Ki‐67 index evaluated on fine‐needle aspiration (FNA) specimens can correlate with the mitotic rate of GIST in surgical specimens and provide further risk assessment.

Methods

Cases with cell blocks containing adequate tumor cells and surgical resections were included. Ki‐67 immunostain was retrospectively performed on cell block sections, and Ki‐67 index was calculated on the “hot spot” areas.

Results

This study included 50 GIST cases from stomach (n = 45; 90%), duodenum (n = 4; 8%), and distal esophagus (n = 1; 2%). The tumor size ranged from 1.5 cm to 21 cm (mean, 5.4 cm). Based on the mitotic count, 37 GISTs (74%) had low mitotic rate (LMR) and 13 GISTs (26%) had high mitotic rate (HMR). The spindle cell, epithelioid, and mixed types accounted for 60%, 14%, and 26% of GIST, respectively. Ki‐67 index counted on cell block sections correlated well with mitotic count evaluated in surgical specimens (r = 0.8031). Mean Ki‐67 index was higher in HMR than LMR groups (3.5% vs. 1%, p < .001). The receiver operating characteristic curve using Ki‐67 index to predict mitotic rate was further analyzed, and area under the curve was 0.839. Using a cutoff of 2.5% yielded a sensitivity of 70% at 92% specificity.

Conclusions

This study demonstrates good correlations between Ki‐67 index and mitotic count or risk stratification, suggesting that Ki‐67 index evaluated on cytology specimens may offer a promising approach to preoperatively predict the mitotic rate and risk of GIST.
Automated generation of 0D and 1D reduced‐order models of patient‐specific blood flow
Authors: Pfaller Martin R. , Pham Jonathan , Verma Aekaansh , Pegolotti Luca , Wilson Nathan M. , Parker David W. , Yang Weiguang , Marsden Alison L.
Published: July 2022

Three‐dimensional (3D) cardiovascular fluid dynamics simulations typically require hours to days of computing time on a high‐performance computing cluster. One‐dimensional (1D) and lumped‐parameter zero‐dimensional (0D) models show great promise for accurately predicting blood bulk flow and pressure waveforms with only a fraction of the cost. They can also accelerate uncertainty quantification, optimization, and design parameterization studies. Despite several prior studies generating 1D and 0D models and comparing them to 3D solutions, these were typically limited to either 1D or 0D and a singular category of vascular anatomies. This work proposes a fully automated and openly available framework to generate and simulate 1D and 0D models from 3D patient‐specific geometries, automatically detecting vessel junctions and stenosis segments. Our only input is the 3D geometry; we do not use any prior knowledge from 3D simulations. All computational tools presented in this work are implemented in the open‐source software platform SimVascular. We demonstrate the reduced‐order approximation quality against rigid‐wall 3D solutions in a comprehensive comparison with N = 72 publicly available models from various anatomies, vessel types, and disease conditions. Relative average approximation errors of flows and pressures typically ranged from 1% to 10% for both 1D and 0D models, measured at the outlets of terminal vessel branches. In general, 0D model errors were only slightly higher than 1D model errors despite requiring only a third of the 1D runtime. Automatically generated ROMs can significantly speed up model development and shift the computational load from high‐performance machines to personal computers.
CO2 Entropy Depletion‐induced 2D Amorphous Structure in Non‐van der Waals VO2
Authors: Yan Pengfei , Zhou Yannan , Zhang Bin , Xu Qun
Published: July 2022

Few studies focus on the plastic deformations of inorganic semiconductors because they are usually brittle and do not deform easily. Here, a peculiar internal shear stress originated from the entropy deletion of CO2 in the tunnels of non‐van der Waals VO2 crystal, is employed to introduce hierarchical plastic deformations, including dislocations, point vacancies, twins, and amorphous bands. The strength of such stress field increases by more than three orders of magnitude compared to that of external experimental CO2 pressure. We further demonstrate that 2D amorphous structures can be obtained by the synergetic effect of hierarchical deformations in 3D crystal.
Manipulating White‐Light Generation in Adamantane‐Like Molecules via Functional Group Substitution
Authors: Gowrisankar Saravanan , Hosier Christopher A. , Schreiner Peter R. , Dehnen Stefanie
Published: July 2022

Certain adamantane (Ad)‐like molecules, either clusters of the type [(R′T)4E6] with inorganic cores (R′=cyclic/aromatic organic substituent; T=Si, Ge, Sn; E=S, Se, Te) or adamantane derivatives [(R′C)4(CH2)6]=AdR′4, display extreme nonlinear optical properties, which can lead to white‐light emission when exposed to near infrared light. While previous studies have established some requirements for these compounds to generate white light, the ability to tailor this effect remains elusive. Here we evaluate the impact of a variety of inorganic and organic compounds with Ad‐like cores as well as various functional groups on white‐light generation (WLG). We show that polarization and electron density localization are influenced by the type of the functional group R in [(R‐PhSn)4S6] in particular, according to DFT computations. While these groups do not have a large impact on the maximum emission wavelengths, they do significantly affect the laser power threshold for the occurrence of WLG.
Decomposition of Deep Eutectic Solvent Aids Metals Extraction in Lithium‐Ion Batteries Recycling
Authors: Schiavi Pier Giorgio , Altimari Pietro , Sturabotti Elisa , Giacomo Marrani Andrea , Simonetti Giulia , Pagnanelli Francesca
Published: July 2022

The application of deep eutectic solvents (DESs) to dissolve metal oxides in lithium‐ion batteries (LIBs) recycling represents a green technological alternative to the mineral acids employed in hydrometallurgical recycling processes. However, DESs are much more expensive than mineral acids and must be reused to ensure economic feasibility of LIB recycling. To evaluate DES reusability, the role of the choline chloride‐ethylene glycol DES decomposition products on metal oxides dissolution was investigated. The temperatures generally applied to carry on this DES leaching induced the formation of decomposition products that ultimately improved the ability to dissolve LIB metal oxides. The characterization of DES decomposition products revealed that the improved metal dissolution was mainly determined by the formation of Cl3−, which was proposed to play a pivotal role in the oxidative dissolution of LIB metal oxides.
Circular RNA circ‐TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA
Authors: Pan Xiaojuan , Huang Bo , Ma Qiang , Ren Junwu , Liu Yuying , Wang Cong , Zhang Dawei , Fu Jian , Ran Lingyu , Yu Ting , Li Haiping , Wang Xiaolin , Yang Feifei , Liang Ce , Zhang Yuying , Wang Shimin , Ren Jingjing , Li Wei , Wang Yongquan , Xiao Bin
Published: July 2022

Background

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumour of the urinary tract. The major causes of poor prognosis are the lack of early diagnosis and metastasis. Accumulating research reveals that circular RNAs (circRNAs) can play key roles in the development and the progression of cancer. However, the role of circRNAs in ccRCC is still uncertain.

Methods

The circRNAs microarray (n = 4) was performed to investigate the circRNAs with differential expression in ccRCC tissues. The candidate circRNA was selected based on the cut‐off criteria, such as circRNA expression abundance, circRNA size and the design of divergent primers. The circ‐transportin‐3 (TNPO3) levels in ccRCC tissues were tested by quantitative real‐time (qRT)‐PCR (n = 110). The characteristics and subcellular localization of circ‐TNPO3 were identified via RNase R assay, qRT‐PCR and fluorescence in situ hybridization (FISH). Then, we explored the biological roles of circ‐TNPO3 in ccRCC via the function experiments in vitro and in vivo. RNA pull‐down, RNA immunoprecipitation, bioinformatic analysis, RNA‐FISH assays and rescue assays were applied to validate the interactions between circ‐TNPO3, insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) and serpin family H member 1 (SERPINH1) to uncover the underlying molecular mechanisms of circ‐TNPO3.

Results

We detected the obvious downregulation of circ‐TNPO3 in ccRCC compared to matched adjacent normal tissues (n = 110). The lower circ‐TNPO3 expression was found in ccRCC patients with distant metastasis, higher World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) grade and more advanced tumour T stage. In vitro and in vivo, circ‐TNPO3 significantly suppressed the proliferation and migration of ccRCC cells. Mechanistically, we elucidated that circ‐TNPO3 directly bound to IGF2BP2 protein and then destabilized SERPINH1 mRNA. Moreover, IGF2BP2/SERPINH1 axis was responsible for circ‐TNPO3's function of inhibiting ccRCC metastasis. Epithelial splicing regulatory protein 1 (ESRP1) was probably involved in the biogenesis of circ‐TNPO3.

Conclusions

Circ‐TNPO3 can suppress ccRCC progression and metastasis via directly binding to IGF2BP2 protein and destabilizing SERPINH1 mRNA. Circ‐TNPO3 may act as a potential target for ccRCC treatment.
A resveratrol derivative modulates TRH and TRH‐like peptide expression throughout the brain and peripheral tissues of male rats
Authors: Pekary Albert Eugene , Sattin Albert
Published: July 2022

Introduction

Resveratrol and related polyphenols have therapeutic effects ranging from treatment of depression, Alzheimer's and Parkinson's disease, obesity, diabetes, neurodegeneration and ageing. TRH and TRH‐like peptides, with the structure pGlu‐X‐Pro‐NH2, where ‘X can be any amino acid reside, have reproductive, caloric‐restriction‐like, anti‐ageing, pancreatic‐β cell‐enhancing, cardiovascular and neuroprotective effects. We hypothesize that TRH and TRH‐like peptides are mediators of the therapeutic actions of the resveratrol derivative pterostilbene (PT).

Methods

Sixteen young adult male Sprague–Dawley rats were divided into four groups. Control group remained on ad libitum chow and water for 10 days. Acute group received ad libitum chow and water for 9 days and then 0.9 g PT/250 g rat chow for 24 h. Chronic animals received PT in chow for 10 days. Withdrawal rats received PT chow for 8 days and then normal chow for 2 days. TRH and TRH‐like peptide levels were measured in medulla oblongata (MED), frontal cortex (FCX), hypothalamus (HY), amygdala (AY), hippocampus (HC), piriform cortex (PIR), nucleus accumbens (NA), entorhinal cortex (ENT), striatum (STR), cerebellum (CBL), anterior cingulate (ACNG), posterior cingulate (PCNG), prostate (PR), liver (L), testis (T), heart (H), pancreas (PAN), adrenals (AD) and epididymis (EP).

Results

Significant changes in the levels of TRH and TRH‐like peptides occurred throughout the brain and peripheral tissues in response to PT treatment.

Conclusion

The high responsiveness of PIR, CBL, HY, STR, PCNG, MED, FCX, NA, ACNG and AY in brain and EP and PR is consistent with TRH and TRH‐like peptides participating in the therapeutic effects of PT.
Exploring the Impact of Lone Pairs on the Structural Features of Alkaline‐Earth (A) Transition‐Metal (M,M’) Chalcogenides (Q) AMM'Q3
Authors: Eickmeier Katharina , Poschkamp Ruben , Dronskowski Richard , Steinberg Simon
Published: July 2022

Understanding electronic structures is decisive for the design of solid‐state materials, as its knowledge is providing invaluable information regarding the chemical and physical properties. One aspect of steady interest in electronic structure theory is the influence of lone pairs on the structural arrangements in a given solid. Herein, we report on explorations of the impact of lone pairs on the structural features of members belonging to a prolific family of alkaline‐earth‐metal (A) transition‐metal (M,M’) chalcogenides (Q). The outcome indicates that the aspects controlling the structural preferences in the inspected AMM'Q3‐type tellurides are rather subtle. In addition to the results of our first‐principles‐based investigations, we also provide a brief overview about the structural features for these tellurides including two new representatives which have been obtained from high‐temperature solid‐state reactions for the very first time.
Advances in the Synthesis of Biscarboranes
Authors: Cao Ke , Zhang Cai‐Yan
Published: July 2022

Biscarboranes are comprised of two carborane units linked with a C−C, B−B or C−B bond, which have important applications in functional materials, coordination chemistry as well as metallacarboranes. Except the well‐developed 1,1′‐bis(o‐carborane), the biscarboranes linked with B−B and C−B bond are still rarely explored due to the limited synthetic methods. This review summarizes the methods for synthesis of biscarboranes in the past half century and recent advances thereof.
Evaluation of Three ISO Estrogen Receptor Transactivation Assays Applied to 52 Domestic Effluent Samples
Authors: Simon Eszter , Riegraf Carolin , Schifferli Andrea , Olbrich Daniel , Bucher Thomas , Vermeirssen Etiënne L. M.
Published: July 2022

Estrogens are released to the aquatic environment by wastewater treatment plant (WWTP) effluents and can affect wildlife. In the last three decades, many in vitro assay platforms have been developed to detect and quantify estrogenicity in water. In 2018, the International Organization for Standardization (ISO) standardized protocols became available for three types of in vitro estrogen receptor transactivation assays (ERTAs) detecting estrogenicity in 96-well plates (ISO19040 1-3). Two ERTAs—lyticase Yeast Estrogen Screen (L-YES) and Arxula YES (A-YES)—use genetically modified yeast strains, whereas the third utilizes stably transfected human cells. One human cell based assay is ERα-CALUX, which is based on a genetically modified human bone osteosarcoma cell line. In the present study, we characterized the performance, comparability, and effectiveness of these three ERTAs, including an evaluation involving proposed water quality thresholds (effect-based trigger values [EBTs]). For a robust evaluation, we collected 52 effluent samples over three sampling campaigns at 15 different WWTPs in Switzerland. Estrogen receptor transactivation assay results were correlated and compared with results from chemical analysis targeting known estrogens. The three ERTAs showed comparable data over all campaigns. However, the selection of EBTs plays a significant role in the interpretation and comparison of bioassay results to distinguish between acceptable and unacceptable water quality. Applying a fixed cross-assay EBT for effluent of 4 ng L−1 resulted in varying numbers of threshold exceedances ranging between zero and four samples depending on the ERTA used. Using assay-specific EBTs showed exceedances in eight samples (ERα-CALUX) and in one sample (A-YES), respectively. Thus, proposed EBTs do not produce similar risk profiles across samples and further refinement of assay-specific EBTs is needed to account for assay-specific differences and to enable the application of ERTAs as effect-based methods in environmental monitoring. Environ Toxicol Chem 2022;41:2512–2526. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Comparison of three ISO19040 in vitro estrogen receptor transactivation assays (ERα-CALUX, lyticase Yeast Estrogen Screen [L-YES] and Arxula YES [A-YES]) based on 52 wastewater treatment plant (WWTP) effluent extracts. In addition, bioassays results were compared with results from chemical analysis using liquid chromatography–mass spectrometry (LC-MS/MS) targeting known estrogens.
Joint bandwidth and power resource allocation technique in multi‐carrier non‐orthogonal multiple access‐based cognitive Internet of Things networks
Authors: Bany Salameh Haythem , Al‐Obiedollah Haitham , Arabiat Themar , Al‐ajlouni Ahmad , Jararweh Yaser
Published: July 2022

The recent development of the Internet of Things (IoT) devices offers an intelligent concept for integrating massive number of interconnected wireless devices. However, supporting such massive number of IoT connections (hundreds of billions) requires an efficient and dynamic spectrum access strategy. Accordingly, the integration of non‐orthogonal multiple access (NOMA) in the cognitive radio (CR) systems, referred to as a multi‐carrier NOMA CR‐enabled system, is envisioned as a potential spectrum‐efficient networking paradigm that can support massive energy‐efficient IoT connectivity in B5G networks while maintaining the quality of services (QoS) of the IoT devices. However, the power consumption issue of the multi‐carrier NOMA CR‐based system becomes as one of key challenges, especially when considering the expected massive connectivity. Accordingly, several power‐aware optimization frameworks have been considered to address this issue. While most of the existing CR‐based multi‐carrier NOMA power allocation mechanisms only optimize the allocated per‐user power, this article proposes a novel joint bandwidth and power allocation problem over each available idle channel with the aim of minimizing the overall transmission power under a set of QoS constrains. Specifically, the bandwidth of each channel is adaptively subdivided into two variable‐width sub‐channels, each is capable to serve a group of CR users using power‐domain NOMA. This novel design is formulated as a joint optimization problem that is shown to be a non‐convex. Therefore, an iterative algorithm with a second‐order cone programming is deployed to handle the non‐convexity of the problem, and thus, determine the solution of it. Simulation results reveal that the developed variable bandwidth adaptive power allocation mechanism outperforms the conventional equal sub‐channel allocation in terms of the required transmission power, which significantly improves the energy efficiency in the system.
A need for standardized reporting of introgression: Insights from studies across eukaryotes
Authors: Dagilis Andrius J. , Peede David , Coughlan Jenn M. , Jofre Gaston I. , D'Agostino Emmanuel R. R. , Mavengere Heidi , Tate Alexander D. , Matute Daniel R.
Published: July 2022

With the rise of affordable next-generation sequencing technology, introgression—or the exchange of genetic materials between taxa—has become widely perceived to be a ubiquitous phenomenon in nature. Although this claim is supported by several keystone studies, no thorough assessment of the frequency of introgression across eukaryotes in nature has been performed to date. In this manuscript, we aim to address this knowledge gap by examining patterns of introgression across eukaryotes. We collated a single statistic, Patterson's D, which can be used as a test for introgression across 123 studies to further assess how taxonomic group, divergence time, and sequencing technology influence reports of introgression. Overall, introgression has mostly been measured in plants and vertebrates, with less attention given to the rest of the Eukaryotes. We find that the most frequently used metrics to detect introgression are difficult to compare across studies and even more so across biological systems due to differences in study effort, reporting standards, and methodology. Nonetheless, our analyses reveal several intriguing patterns, including the observation that differences in sequencing technologies may bias values of Patterson's D and that introgression may differ throughout the course of the speciation process. Together, these results suggest the need for a unified approach to quantifying introgression in natural communities and highlight important areas of future research that can be better assessed once this unified approach is met.
Joule heating effect on radiating MHD mixed convection stagnation point flow along vertical stretching sheet embedded in a permeable medium and heat generation/absorption
Authors: Mehta Ruchika , Kumar Ravindra , Rathore Himanshu , Singh Jagdev
Published: July 2022

The goal of this study is to investigate magnetohydrodynamics varied convective stagnation point stream with a vertically extended sheet embedded in a permeable material. Warmth generation/absorption, radiation impacts, and viscous dissipation are all considered. Using the process of likeness change, the principal boundary layer equations are written and turned into nonlinear ordinary joined differential equations, and the numerical result is produced using the Runge–Kutta fourth‐order approach via shooting technique. Varied physical limits have different effects, such as velocity fraction restriction, mixed convection restriction, Hartmann numeral, Prandtl numeral, permeability restriction, warm air radiation restriction, hotness generation/absorption restriction, and so on, over velocity and temperature scatterings are introduced graphically and then mathematically. The skin friction constant, in addition to Nusselt numerals, over the sheet is determined, expressed mathematically as well as introduced through tables. Fluid velocity and temperature increase with radiation restriction Ra. Skin friction and Nusselt numeral are increasing functions of Hartmann numeral Ha, and decreasing ones of permeability restriction K.
The Effects of Acute High‐Intensity Interval Exercise and Hyperinsulinemic‐Euglycemic Clamp on Osteoglycin Levels in Young and Middle‐Aged Men
Authors: Bauer Carlie , Tacey Alexander , Garnham Andrew , Smith Cassandra , Woessner Mary N , Lin Xuzhu , Zarekookandeh Navabeh , Hare David L , Lewis Joshua R , Parker Lewan , Levinger Itamar
Published: July 2022

Osteoglycin (OGN) is a leucine‐rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high‐intensity interval exercise (HIIE) and hyperinsulinemic‐euglycemic clamp on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio‐metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle‐aged obese men (58.1 ± 2.2 years, body mass index [BMI] = 33.1 ± 1.4 kg∙m−2, mean ± SEM) and 9 young men (27.8 ± 1.6 years, BMI = 24.4 ± 0.08 kg∙m−2) who previously completed a study involving a euglycemic‐hyperinsulinemic clamp at rest and after HIIE (4x4 minutes cycling at approximately 95% peak heart rate (HRpeak), interspersed with 2 minutes of active recovery). Blood pressure, body composition (dual‐energy X‐ray absorptiometry), and insulin sensitivity (hyperinsulinemic‐euglycemic clamp) were assessed. Serum OGN was higher in the young cohort compared with the middle‐aged cohort (65.2 ± 10.1 ng/mL versus 36.5 ± 4. 5 ng/mL, p ≤ 0.05). Serum OGN was unaffected by acute HIIE but decreased after the insulin clamp compared with baseline (~−27%, p = 0.01), post‐exercise (~−35%, p = 0.01), and pre‐clamp (~−32%, p = 0.02) time points, irrespective of age. At baseline, lower circulating OGN levels were associated with increased age, BMI, and fat mass, whereas higher OGN levels were related to lower fasting glucose. Higher OGN levels were associated with a higher glucose infusion rate. Exercise had a limited effect on circulating OGN. The mechanisms by which OGN affects glucose regulation should be explored in the future. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Foldscope microscope, an inexpensive alternative tool to conventional microscopy—Applications in research and education: A review
Authors: Ganesan Mijithra , Selvan Christyraj Johnson Retnaraj Samuel , Venkatachalam Saravanakumar , Yesudhason Beryl Vedha , Chelladurai Karthikeyan Subbiahanadar , Mohan Manikandan , Kalimuthu Kalishwaralal , Narkhede Yogesh B. , Christyraj Jackson Durairaj Selvan
Published: July 2022

Microscope is a device used for the visualization of tiny objects which are not visible to the naked eye. Traditional microscopes have been crucial for the advancement of contemporary science and medicine. Recent advancements in the field of microscopy have fueled its exponential growth rate. However, due to their expensive cost and complicated structure, modern microscopes remain inaccessible to the majority of the public. Nonetheless, the foldscope paper microscope has made it possible for anyone to explore and understand the world of microbes and organisms. In this review, we have listed foldscope‐based research projects in various domains, as well as their key properties when compared to traditional research microscopes. In addition, we have briefly explored the impact of a foldscope microscope on public health, clinical diagnostics, forensic science, agriculture, basic science, developmental biology, and education. Moreover, the major drawbacks of paper microscopes and the current steps being taken to upgrade foldscope and its features are discussed in this review. Finally, we have concluded with our perspective that the microscope may be updated to imitate the advancement of a conventional microscope.

Research Highlights

The foldscope, a low‐cost instrument for studying the microscopic world.

Foldscope applications were compared to conventional microscopes in many sectors.

The foldscope microscope's existing limitations and potential prospects are highlighted.
Automatic skin lesions detection from images through microscopic hybrid features set and machine learning classifiers
Authors: Alyami Jaber , Rehman Amjad , Sadad Tariq , Alruwaythi Maryam , Saba Tanzila , Bahaj Saeed Ali
Published: July 2022

Skin cancer occurrences increase exponentially worldwide due to the lack of awareness of significant populations and skin specialists. Medical imaging can help with early detection and more accurate diagnosis of skin cancer. The physicians usually follow the manual diagnosis method in their clinics but nonprofessional dermatologists sometimes affect the accuracy of the results. Thus, the automated system is required to assist physicians in diagnosing skin cancer at early stage precisely to decrease the mortality rate. This article presents an automatic skin lesions detection through a microscopic hybrid feature set and machine learning‐based classification. The employment of deep features through AlexNet architecture with local optimal‐oriented pattern can accurately predict skin lesions. The proposed model is tested on two open‐access datasets PAD‐UFES‐20 and MED‐NODE comprising melanoma and nevus images. Experimental results on both datasets exhibit the efficacy of hybrid features with the help of machine learning. Finally, the proposed model achieved 94.7% accuracy using an ensemble classifier.

Research highlights

The deep features accurately predicted skin lesions through AlexNet architecture with local optimal‐oriented pattern.

Proposed model is tested on two datasets PAD‐UFES‐20, MED‐NODE comprising melanoma, nevus images and exhibited high accuracy.
A qualitative study of unaffected ATM and CHEK2 carriers: How participants make meaning of ‘moderate risk’ genetic results in a population breast cancer screening trial
Authors: James Jennifer Elyse , Riddle Leslie , Caruncho Mikaella , Koenig Barbara Ann , Joseph Galen
Published: July 2022

Relatively little is known about experiences of individuals with a pathogenic variant in a moderately penetrant breast cancer gene, particularly those without a personal history of cancer. The WISDOM trial is testing a model of risk‐based breast cancer screening that integrates genomic (nine genes and polygenic risk) and other risk factors. In the context of an embedded Ethical, Legal, and Social Implications (ELSI) study of WISDOM, we conducted qualitative interviews at two timepoints post‐result disclosure with 22 ATM and CHEK2 carriers. Results disclosure and interview recordings were transcribed and analyzed using a grounded theory analysis framework. We found that participants minimized the significance of their results in comparison to BRCA; were surprised but not alarmed by the results in the absence of family history; did not fundamentally change their perception of their breast cancer risk despite the new genomic information; exhibited variable responses to WISDOM’s screening and risk reduction recommendations; and shared test results with family but did not strongly encourage cascade testing. Participants viewed the results as having limited utility and responded accordingly. Our study offers important insights into how genetic test results for moderate‐risk genes are received, understood, and acted upon in population screening context.
High rates of treatment stage migration for early hepatocellular carcinoma and association with adverse outcomes: An Australian multicenter study
Authors: Loo Kee Fong , Woodman Richard J , Bogatic Damjana , Chandran Vidyaleha , Muller Kate , Chinnaratha Mohamed Asif , Bate John , Campbell Kirsty , Maddison Matthew , Narayana Sumudu , Le Hien , Pryor David , Wigg Alan
Published: July 2022

Background and Aim

The rate of contraindications to percutaneous ablation (PA) for inoperable early hepatocellular carcinoma (HCC) and subsequent outcomes is not well described. We investigated the prevalence and outcomes of inoperable early HCC patients with contraindications to PA, resulting in treatment stage migration (TSM).

Methods

Barcelona Clinic Liver Cancer (BCLC) 0/A patients diagnosed between September 2013 and September 2019 across five hospitals were identified. Primary endpoint was proportion of BCLC 0/A HCCs with contraindications to PA. Secondary endpoints included overall survival (OS), local tumor control (LTC), and recurrence‐free survival (RFS). The causal effects of PA versus TSM were assessed using a potential outcome means (POM) framework in which the average treatment effects (ATEs) of PA were estimated after accounting for potential selection bias and confounding.

Results

Two hundred twenty patients with inoperable BCLC 0/A HCC were identified. One hundred twenty‐two patients (55.5%) had contraindications to PA and received TSM therapy, 98 patients (44.5%) received PA. The main contraindication to PA was difficult tumor location (51%). Patients who received TSM therapy had lower median OS (2.4 vs 5.3 years), LTC (1.0 vs 4.8 years), and RFS (0.8 vs 2.9 years); P < 0.001, respectively, compared with PA. The ATE for PA versus TSM yielded an additional 1.11 years (P = 0.019), 2.45 years (P < 0.001), and 1.64 years (P < 0.001) for OS, LTC, and RFS, respectively. Three‐year LTC after PA was suboptimal (65%).

Conclusion

Our study highlights high rates of contraindication to PA in early HCCs, resulting in TSM and poorer outcomes. The LTC rate for PA appears suboptimal despite being considered as curative therapy. Both findings support the exploration of improved treatment options for early HCCs.
Acceptability and feasibility of leveraging community‐based HIV counselling and testing platforms for same‐day oral PrEP initiation among adolescent girls and young women in Eastern Cape, South Africa
Authors: Medina‐Marino Andrew , Bezuidenhout Dana , Ngwepe Phuti , Bezuidenhout Charl , Facente Shelley N. , Mabandla Selly , Hosek Sybil , Little Francesca , Celum Connie L. , Bekker Linda‐Gail
Published: July 2022

Introduction

Community‐based delivery of HIV pre‐exposure prophylaxis (PrEP) to South African adolescent girls and young women's (AGYW) could increase access but needs evaluation. We integrated PrEP services via home‐based services and pop‐up tents into existing community‐based HIV testing services (CB‐HTS) in Eastern Cape Province, South Africa.

Methods

After accessing CB‐HTS via a “pop‐up” tent or home‐based services, HIV‐negative AGYW aged 16–25 years were invited to complete a baseline questionnaire and referred for PrEP services at a community‐based PrEP site co‐located with pop‐up HTS tents. A 30‐day supply of PrEP was dispensed. PrEP uptake, time‐to‐initiation, cohort characteristics and first medication refill within 90 days were measured using descriptive statistics.

Results

Of the 1164 AGYW who tested for HIV, 825 (74.3%) completed a questionnaire and 806 (97.7%) were referred for community‐based PrEP. Of those, 624 (77.4%) presented for PrEP (482/483 [99.8%] from pop‐up HTS and 142/323 [44.0%] from home‐based HTS), of which 603 (96.6%) initiated PrEP. Of those initiating PrEP following home‐based HTS, 59.1% initiated within 0–3 days, 25.6% within 4–14 days and 15.3% took ≥15 days to initiate; 100% of AGYW who used pop‐up HTS initiated PrEP the same day. Among AGWY initiating PrEP, 37.5% had a detectable sexually transmitted infection (STI). Although AGYW reported a low self‐perception of HIV risk, post‐hoc application of HIV risk assessment measures to available data classified most study participants as high risk for HIV acquisition. Cumulatively, 329 (54.6%) AGYW presented for a first medication refill within 90 days of accepting their first bottle of PrEP.

Conclusions

Leveraging CB‐HTS platforms to provide same‐day PrEP initiation and refill services was acceptable to AGYW. A higher proportion of AGYW initiated PrEP when co‐located with CB‐HTS sites compared to those referred following home‐based HTS, suggesting that proximity of CB‐HTS and PrEP services facilitates PrEP uptake among AGYW. The high prevalence of STIs among those initiating PrEP necessitates the integration of STI and HIV prevention programs for AGYW. Eligibility for PrEP initiation should not be required among AHYW in high HIV burden communities. Community‐based service delivery will be crucial to maintaining access to PrEP services during the COVID‐19 pandemic and future health and humanitarian emergencies.
Aging Effect, Reproducibility, and Test–Retest Reliability of a New Cerebral Amyloid Angiopathy MRI Severity Marker—Cerebrovascular Reactivity to Visual Stimulation
Authors: van Dijk Suzanne E. , Lak Jessie , Drenth Nadieh , Hafkemeijer Anne , Rombouts Serge A.R.B. , van der Grond Jeroen , van Rooden Sanneke
Published: July 2022

Background

Decreased cerebrovascular reactivity, measured as changes in blood‐oxygen‐level‐dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test–retest reliability of these parameters should be assessed.

Purpose

Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test–retest reliability of these parameters.

Study Type

Prospective‐observational.

Population

Eighty‐six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D‐CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D‐CAA mutation carriers (mean age 54 years, 70% female).

Field Strength/Sequence

3‐T, three‐dimensional (3D) T1‐weighted MRI and gradient echo BOLD fMRI.

Assessment

To assess test–retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3‐week interval for each subject.

Statistical Tests

Linear regression analyses and two‐way mixed absolute agreement intra‐class correlation approach.

Results

Healthy aging was associated with decreased BOLD amplitude (β = −0.711) and prolonged time to baseline (β = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test–retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856–0.910) and presymptomatic D‐CAA mutation carriers (ICC 0.959–0.981). In symptomatic D‐CAA mutation carriers, test–retest reliability was poor for all parameters (ICCs < 0.5).

Data Conclusion

Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D‐CAA mutation carriers, but not in symptomatic D‐CAA mutation carriers.
Epidemiology and genetic characterization of human metapneumovirus in pediatric patients from Hangzhou China
Authors: Du Yun , Li Wei , Guo Yajun , Li Lin , Chen Qiang , He Lin , Shang Shiqiang
Published: July 2022

Human metapneumovirus (HMPV), which is distributed worldwide, is a significant viral respiratory pathogen responsible for causing acute respiratory tract infections (ARTIs) in children. The aim of the present study was to investigate the epidemiological and genetic characteristics of HMPV in pediatric patients in Hangzhou China following the peak of onset of coronavirus disease 2019 (COVID‐19). A total of 1442 throat swabs were collected from the pediatric patients with a diagnosis of ARTI from November 2020 to March 2021. The following viruses were detected by real‐time polymerase chain reaction analysis: HMPV, RSV, adenovirus, hPIV1‐3, influenza A, and influenza B. A two‐step method was used to amplify the F genes of the HMPV‐positive samples. Following sequencing, phylogenetic analyses were conducted using the MEGA version 7 software package. Among the 1442 samples, 103 (7.14%) were positive for HMPV. No significant differences were observed in the gender distribution. The highest incidence of HMPV occurred in children older than 6 years and the lowest was noted in children younger than 6 months. Lower respiratory tract infections were diagnosed at a higher rate than upper respiratory tract infections in HMPV‐infected children. Only 10 HMPV‐infected children (5.41%) were inpatients compared with 93 outpatients (7.39%). Co‐infection was observed in 31 HMPV‐positive samples including 24 samples of double infection and seven samples of triple infection. A total of 61F gene fragments of HMPV, which were approximately 727 bp in length were successfully sequenced. All the HMPVs belonged to the genotype B and were clustered into subgenotypes B1 (1.6%, 1/61) and B2 (98.4%, 60/61). A total of four specific amino acid substitutions were noted as follows: aa280, aa296, aa392, and aa396. These substitutions were present between sequences derived from the subgenotypes B1 and B2 in the fusion open reading frame from position 244 to 429. In conclusion, the present study provided significant information regarding the epidemiological and genetic characteristics of HMPV in children living in Hangzhou. Following the first peak of the COVID‐19 pandemic, HMPV was considered an important viral respiratory pathogen present in children with ARTI.
Smectic C Self‐Assembly in Mesogen‐Free Liquid Crystalline Chiral Polyethers with Sulfonylated Methyl‐Branched Side Chains
Authors: Bohannon Caleb A. , Kwok Man‐Hin , Huang Jiahao , Rui Guanchun , Li Ruipeng , Zhu Lei , Zhao Bin
Published: July 2022

To realize advanced electrical applications for ferroelectric liquid crystalline polymers, high spontaneous polarization (Ps) is highly desired. However, current ferroelectric liquid crystalline polymers usually exhibit a low Ps. In this work, mesogen‐free, chiral polyethers containing sulfonylated methyl‐branched alkyl side chains with a (CH2)3O spacer between the sulfonyl and the branched alkyl groups are designed and synthesized. In contrast to the linear n‐alkyl side chains, the methyl‐branched alkyl side chains induce chain tilting in the smectic layers. When double chirality exists in both the main chain and the side chains, a crystalline structure is observed after mechanical stretching. Intriguingly, when single chirality exists in either the backbone or the side chains, a liquid crystalline smectic C phase is obtained. The electric displacement–electric field study, however, does not show typical ferroelectric switching, although the dielectric constants are relatively high for these liquid crystalline polymers. This is likely because the dipole–dipole interactions among neighboring sulfonyl groups along the main chain are so strong that the ferroelectric switching is hindered in the samples. For the future work, it is desired to weaken the dipole–dipole interaction to achieve ferroelectricity in these mesogen‐free liquid crystalline polymers.
The Prevalence of Idiopathic or Inherited Isolated Dystonia: A Systematic Review and Meta‐Analysis
Authors: Medina Alex , Nilles Christelle , Martino Davide , Pelletier Catherine , Pringsheim Tamara
Published: July 2022

Background

A systematic review of epidemiological studies of primary dystonia from 1985 and 2010 found an overall prevalence of 16.43 per 100,000 (95% CI = 12.09–22.32).

Methods

We performed a systematic review of studies from 2010 and 2022 to determine if there are important differences in epidemiology between these time periods.

Results

Nineteen studies were included. Incidence of cervical dystonia, blepharospasm, and oromandibular dystonia were each reported in one study; one study reported incidence for all adult onset idiopathic focal dystonias combined. Using data from 11 studies, we performed random effects meta‐analyses of the prevalence of cervical dystonia (9.95 per 100,000; 95% CI = 3.51–28.17), blepharospasm (2.82 per 100,000; 95% CI = 1.12–7.12), laryngeal dystonia (0.40 per 100,000; 95% CI = 0.09–1.83), upper limb dystonia (1.27 per 100,000; 95% CI = 0.36–4.52), oromandibular dystonia (0.57 per 100,000; 95% CI = 0.15–2.15), and idiopathic or inherited isolated dystonia all subtypes combined (30.85 per 100,000; 95% CI = 5.06–187.74). All studies reported more cases of dystonia in females. There was no significant difference in prevalence by subgroup analysis based on time of study publication (1985–2010 vs. 2010–2022). Subgroup analysis of differences in prevalence by dystonia subtype by continent using all studies published (1985–2022) revealed significant regional differences in the prevalence of cervical and laryngeal dystonia.

Conclusion

The incidence and prevalence of idiopathic or inherited isolated dystonia in the last decade was not significantly different from earlier reports. Population‐based studies across multiple geographic areas are needed to obtain a clearer understanding of the epidemiology of this condition.
RFC1‐Related Disorder: In Vivo Evaluation of Spinal Cord Damage
Authors: Rezende Thiago J.R. , Schmitt Gabriel S. , de Lima Fabricio D. , de Brito Mariana Rabelo , Matos Paula Camila A.A.P. , Bonadia Luciana Cardoso , Martinez Alberto R.M. , Cendes Fernando , Pedroso José Luiz , Barsottini Orlando G.P. , Marques Wilson , França Marcondes Cavalcante
Published: July 2022

Background

RFC1‐related disorder is a novel heredodegenerative condition with a broad phenotypic spectrum. Its neuropathological bases are not yet fully understood, particularly regarding the pattern, extent, and clinical relevance of spinal cord (SC) damage.

Objectives

The objectives were to determine the SC structural signature in RFC1‐related disorder in vivo and to identify potential clinical correlates for these imaging abnormalities.

Methods

We enrolled 17 subjects with biallelic RFC1 (AAGGG)n expansions and 11 age‐ and sex‐matched healthy controls that underwent multimodal magnetic resonance imaging SC acquisitions in a 3T Philips Achieva scanner. Both global morphometry and tract‐specific analyses were then performed across all cervical levels. Between‐group comparisons were assessed using nonparametric tests.

Results

In the patient group, mean age and disease duration were 62.9 ± 9.3 and 9.3 ± 4.0, respectively. Compared to controls, patients had remarkable SC cross‐sectional area reduction along all cervical levels but anteroposterior flattening only in the lower cervical levels. There was also prominent SC gray matter atrophy. Diffusivity abnormalities were identified in the dorsal columns but not in the lateral corticospinal tracts. Disease severity did not correlate with these imaging parameters.

Conclusion

SC damage is a hallmark of RFC1‐related disorder and characterized by gray as well as white matter involvement. In particular, dorsal columns are severely and diffusely affected. The clinical correlates of these imaging abnormalities still deserve additional investigations. © 2022 International Parkinson and Movement Disorder Society.