bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and Analysis of a Compact Piezo-Actuated Microgripper With a Large Amplification Ratio
Authors: Chen Fangxin , Zhang Qianjun , Gao Yongzhuo , Dong Wei 
Published: November 2021

Abstract
This article presents a piezo-actuated microgripper characterized by large amplification ratio and compact structure size. The microgripper is actuated by a piezo-stack actuator that is integrated with a two-stage displacement amplifier to achieve large travel range. A new design methodology “flexure hinge individualized design” (FHID) was proposed to realize large amplification ratio. According to this methodology, each flexure hinge was designed personally based on force condition of the piviot to reconfigure the motion stiffness of the compliant microgripper so that the parasitic motion and displacement loss could be eliminated. Consequently, a 52-amplification ratio amplifier was obtained. The developed microgripper was modeled via kinematics and Castigliano’s displacement theorem, respectively. Finite element analysis and the experimental studies were conducted to evaluate the characteristics of the microgripper. The results show that the motion stroke of the gripper tip is 917 μm, and the structure dimension is 62 mm × 42 mm × 12 mm. The design methodology FHID is generic and can be extended to other compliant mechanisms.
Modeling and Analysis of a Soft Endoluminal Inchworm Robot Propelled by a Rotating Magnetic Dipole Field
Authors: Steiner Jake A. , Pham Lan N. , Abbott Jake J. , Leang Kam K. 
Published: November 2021

Abstract
In clinical practice, therapeutic and diagnostic endoluminal procedures of the human body often use a scope, catheter, or passive pill-shaped camera. Unfortunately, such devices used in the circulatory system and gastrointestinal tract are often uncomfortable, invasive, and require the patient to be sedated. With current technology, regions of the body are often inaccessible to the clinician. Herein, a magnetically actuated soft endoluminal inchworm robot that may extend clinicians’ ability to reach further into the human body and practice new procedures is described, modeled, and analyzed. A detailed locomotion model is proposed that takes into account the elastic deformation of the robot and its interactions with the environment. The model is validated with in vitro and ex vivo (pig intestine) physical experiments and is shown to capture the robot’s gait characteristics through a lumen. Utilizing dimensional analysis, the effects of the mechanical properties and design variables on the robot’s motion are investigated further to advance the understanding of this endoluminal robot concept.
“Negative Things That Kids Should Never Have to Hear”: Exploring Women’s Histories of Weight Stigma in Physical Activity
Authors: Ashdown-Franks Garcia , Meadows Angela , Pila Eva 
Published: November 2021

Scholars have proposed that cumulative experiences of anti-fat bias and stigma contribute to detrimental physical activity experiences, as well as social and health inequities. The objective of this research was to explore how enacted weight stigma experiences are constructed and impact women’s physical activity experiences long term. Eighteen women who identified as having had negative experiences related to their body weight, shape, or size in physical activity contexts participated in semistructured interviews. Using reflexive thematic analysis, four themes were identified: (a) norms of body belonging, (b) distancing from an active identity, (c) at war with the body, and (d) acts of resistance. These findings deepen understandings of how historical experiences of weight stigma can have longstanding consequences on physical activity cognitions, emotions, and behaviors. To equitably promote physical activity, it is imperative that movement spaces (e.g., fitness centers, sport organizations) both target anti-fat stigma and adopt weight-inclusive principles.
Sociodemographic factors associated with time to discharge for hospitalised patients with asthma and asthma exacerbation using the Ghana Health Service District Information Management System 2 (DHIMS-2) database, 2012–2017
Authors: Narh Clement T , Der Joyce B , Afetor Maxwell , Ofosu Anthony , Blettner Maria , Wollschlaeger Daniel 
Published: November 2021

ObjectiveData on asthma hospitalisations are a useful source of patient morbidity information. In Ghana, the length of stay (LoS) and sociodemographic factors of patients hospitalised for asthma and its exacerbation are understudied. We aimed to investigate the time to discharge and assessed factors associated with length of hospital stays of asthmatics in Ghana.MethodsRetrospective analysis of hospitalised patient with asthma records between 2012 and 2017 from the nationwide Ghana Health Service District Health Information Management System 2 database. We calculated the cumulative incidence function for discharge stratified by age group and sex. Multivariable Cox regression was used to investigate the association of sociodemographic characteristics with the LoS.ResultsOf 19 926 asthma-associated hospitalisations, 730 (3.7%) were due to asthma exacerbation. Overall mean age was 34 years (SD=24.6), in 12 000 (60.2%) hospitalisations, patients were female. There were 224 deaths (1.1%). Median LoS was 2 days (IQR: 1–3) with almost 90% of all patients discharged by the seventh day. Age and region were among the covariates showing significant association with LoS. Age below 10 years (HR: 1.39 (1.11 to 1.78)) was associated with early discharge while comorbidity and health insurance ownership were associated with late discharge (p<0.001). LoS did not vary by sex. Compared with the Greater Accra region, patients in other regions had shorter LoS, especially the Ashanti and Upper West regions (p<0.001). LoS increased annually, but was highest in 2016 (HR: 0.94 (0.90 to 0.98)).ConclusionDisparities in LoS across regions, and an overall increasing annual trend in Ghana call for tailored healthcare resource allocation. Longer LoS implies that patients are often absent from school or work leading to substantial financial and emotional costs to individuals and families.
Malignancy risk of indeterminate mammographic calcification in symptomatic breast clinics
Authors: Bansal Gaurav J , Emanuel Lauren , Kanagasabai Sesha 
Published: November 2021

Abstract

Background
To explore the potential risk factors predicting malignancy in patients with indeterminate incidental mammographic microcalcification and to evaluate the short-term risk of developing malignancy.

Methods
Between January 2011 and December 2015, one hundred and fifty (150) consecutive patients with indeterminate mammographic microcalcifications who had undergone stereotactic biopsy were evaluated. Clinical and mammographic features were recorded and compared with histopathological biopsy results. In patients with malignancy, postsurgical findings and surgical upgrade, if any, were recorded. Linear regression analysis (SPSS V.25) was used to evaluate significant variables predicting malignancy. OR with 95% CIs was calculated for all variables. All patients were followed up for a maximum of 10 years. The mean age of the patients was 52 years (range 33–79 years).

Results
There were a total of 55 (37%) malignant results in this study cohort. Age was an independent predictor of breast malignancy with an OR (95% CI) of 1.10 (1.03 to 1.16). Mammographic microcalcification size, pleomorphic morphology, multiple clusters and linear/segmental distribution were significantly associated with malignancy with OR (CI) of 1.03 (1.002 to 1.06), 6.06 (2.24 to 16.66), 6.35 (1.44 to 27.90) and 4.66 (1.07 to 20.19). The regional distribution of microcalcification had an OR of 3.09 (0.92 to 10.3), but this was not statistically significant. Patients with previous breast biopsies had a lower risk of breast malignancy than patients with no prior biopsy (p=0.034).

Conclusion
Multiple clusters, linear/segmental distribution, pleomorphic morphology, size of mammographic microcalcifications and increasing age were independent predictors of malignancy. Having a previous breast biopsy did not increase malignancy risk.
Effects of parasitism on antipredatory responses and defensive behaviors in the subterranean rodent Ctenomys talarum
Authors: Brachetta V. , Schleich C.E. , Zenuto R.R. 
Published: November 2021

Predation represents an important evolutionary force shaping specific adaptations. Prey organisms present behavioral adaptations that allow them to recognize, avoid, and defend themselves from their predators. In addition to predation, there is a growing consensus about the role of parasitism in the structuring of biological communities. In vertebrates, the effects on hosts include changes in daily activity, feeding, mate selection, reproduction, and modifications in responses to environmental stimuli. These behavioral variations can benefit the parasite (parasitic manipulation), benefit the host, or appear as a side effect of the infection. We evaluated the influence of parasitism on the behavioral and physiological responses of the tuco-tucos of the Talas (Ctenomys talarum Thomas, 1898) to predator cues. We found that individuals exposed to cat odors and immobilization entered less often and spent less time in the transparent arms of elevated maze, exhibiting a preference for protected areas (anxiogenic response). Additionally, we evaluated if the presence of parasites affected antipredatory behaviors in C. talarum (naturally parasitized, deparasitized, or inoculated with Eimeria sp.). We did not find differences among the groups with regards to responses to predator cues. Therefore, while exposure to predator cues triggered a stress response, the manipulation of parasite loads did not modify homeostasis under these experimental conditions.
Exotic facies episodes of a carbonate platform: implications for middle and late Cambrian ecosystems and impact of bioturbation in the Alborz Basin, Iran
Authors: Bayet-Goll Aram , Daraei Mehdi , Geyer Gerd , Neto de Carvalho Carlos , Bahrami Nasrin 
Published: November 2021

Abstract

The sedimentological and ichnological data of the Mila Group in the Alborz Basin, northern Iran indicate that the appearance of exotic facies and resurgence of microbialites resulted from the development of extraordinary palaeoceanographic conditions with widespread environmental stress and enhanced precipitation of CaCO
3
. Inhospitable environmental conditions in the Mila Group platform led to a considerable reduction in ichnodiversity, bioturbation intensity and depth and size of burrows, which led to periods of dominating calcimicrobe ecology. The development of exotic or anachronistic facies started around the Cambrian Stage 4–Wuliuan boundary, probably simultaneous with the SPICE event, whereas the Furongian exotic facies period probably took place simultaneous with the HERB event. Biotic and physico-chemical changes in the ocean during these events may have led as well to the virtual absence of the mixed layer and infaunal ecospace utilization in the deposits of the Mila Group. Nevertheless, the local presence of metazoan-microbial build-ups that established between the two suggested exotic facies developments indicates that these periods started at the Cambrian Stage 4–Wuliuan boundary interval, but a fluctuation of abnormal palaeoceanographic conditions and ambient normal marine conditions took place during the Miaolingian and Furongian in the Alborz Basin as a representative of the northern Gondwanan margin.
High-resolution geophysical imaging of reptile burrows (San Salvador rock iguana, the Bahamas): implications for ichnology and conservation ecology
Authors: Buynevich Ilya V. , Rothfus Thomas A. , Curran H. Allen , Thacker Hayden A. , Peronace Rosa , Kopcznski Karen A. , Gnivecki Perry L. 
Published: November 2021

Abstract

Neoichnological research of terrestrial tracemakers in coastal settings provides important palaeoenvironmental information about their context within the subaerial facies. Here we present the first geophysical dataset of reptile burrows in a carbonate substrate and use it to help visualize parts of the burrows of the Bahamian (San Salvador) rock iguana (
Cyclura rileyi
). High-resolution 800 MHz ground-penetrating radar (GPR) images within an enclosure on San Salvador Island were employed to discriminate between the electromagnetic signal response from subsurface anomalies related to air-dominated voids or live animals within burrows. The dielectric contrast between the carbonate substrate and open burrows was sufficient to identify the majority of the 15–20 cm-wide subsurface extensions of the inclined tunnels in the upper 30–40 cm. Whereas limestone clasts induced some interference, it is possible to differentiate their high-amplitude diffractions from those produced by the iguana burrows. Our research indicates that GPR imaging is a viable, rapid, non-invasive method of visualizing animal burrows, with implications for neoichnology, palaeoichnology, and conservation ecology of semi-fossorial species. Furthermore, the critically endangered status of Bahamian land iguanas, as well as ongoing threats from natural and introduced pressures, highlights the need for research into their ichnological record.
Clonal Hematopoiesis Mutations in Patients with Lung Cancer Are Associated with Lung Cancer Risk Factors
Authors: Hong Wei , Li Ang , Liu Yanhong , Xiao Xiangjun , Christiani David C. , Hung Rayjean J. , McKay James , Field John , Amos Christopher I. , Cheng Chao 
Published: November 2021

AbstractClonal hematopoiesis (CH) is a phenomenon caused by expansion of white blood cells descended from a single hematopoietic stem cell. While CH can be associated with leukemia and some solid tumors, the relationship between CH and lung cancer remains largely unknown. To help clarify this relationship, we analyzed whole-exome sequencing (WES) data from 1,958 lung cancer cases and controls. Potential CH mutations were identified by a set of hierarchical filtering criteria in different exonic regions, and the associations between the number of CH mutations and clinical traits were investigated. Family history of lung cancer (FHLC) may exert diverse influences on the accumulation of CH mutations in different age groups. In younger subjects, FHLC was the strongest risk factor for CH mutations. Association analysis of genome-wide genetic variants identified dozens of genetic loci associated with CH mutations, including a candidate SNP rs2298110, which may promote CH by increasing expression of a potential leukemia promoter gene OTUD3. Hundreds of potentially novel CH mutations were identified, and smoking was found to potentially shape the CH mutational signature. Genetic variants and lung cancer risk factors, especially FHLC, correlated with CH. These analyses improve our understanding of the relationship between lung cancer and CH, and future experimental studies will be necessary to corroborate the uncovered correlations.Significance:Analysis of whole-exome sequencing data uncovers correlations between clonal hematopoiesis and lung cancer risk factors, identifies genetic variants correlated with clonal hematopoiesis, and highlights hundreds of potential novel clonal hematopoiesis mutations.
Inhibition of XPO1 Sensitizes Small Cell Lung Cancer to First- and Second-Line Chemotherapy
Authors: Quintanal-Villalonga Alvaro , Taniguchi Hirokazu , Hao Yuan , Chow Andrew , Zhan Yingqian A. , Chavan Shweta S. , Uddin Fathema , Allaj Viola , Manoj Parvathy , Shah Nisargbhai S. , Chan Joseph M. , Offin Michael , Ciampricotti Metamia , Ray-Kirton Jordana , Egger Jacklynn , Bhanot Umesh , Linkov Irina , Asher Marina , Roehrl Michael H. , Qiu Juan , de Stanchina Elisa , Hollmann Travis J. , Koche Richard P. , Sen Triparna , Poirier John T. , Rudin Charles M. 
Published: November 2021

Abstract

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis and extreme lethality. The backbone of SCLC treatment over the past several decades has been platinum-based doublet chemotherapy, with the recent addition of immunotherapy providing modest benefits in a subset of patients. However, nearly all patients treated with systemic therapy quickly develop resistant disease, and there is an absence of effective therapies for recurrent and progressive disease. Here we conducted CRISPR-Cas9 screens using a druggable genome library in multiple SCLC cell lines representing distinct molecular subtypes. This screen nominated exportin-1, encoded by XPO1, as a therapeutic target. XPO1 was highly and ubiquitously expressed in SCLC relative to other lung cancer histologies and other tumor types. XPO1 knockout enhanced chemosensitivity, and exportin-1 inhibition demonstrated synergy with both first- and second-line chemotherapy. The small molecule exportin-1 inhibitor selinexor in combination with cisplatin or irinotecan dramatically inhibited tumor growth in chemonaïve and chemorelapsed SCLC patient-derived xenografts, respectively. Together these data identify exportin-1 as a promising therapeutic target in SCLC, with the potential to markedly augment the efficacy of cytotoxic agents commonly used in treating this disease.

Significance:
CRISPR-Cas9 screening nominates exportin-1 as a therapeutic target in SCLC, and exportin-1 inhibition enhances chemotherapy efficacy in patient-derived xenografts, providing a novel therapeutic opportunity in this disease.
Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Combination with Ralaniten Analogs for the Treatment of Androgen Receptor–positive Prostate and Breast Cancers
Authors: Tien Amy H. , Sadar Marianne D. 
Published: November 2021

AbstractAndrogen receptor (AR) has essential roles in the growth of prostate cancer and some breast cancers. Inhibition of AR transcriptional activity by targeting its N-terminal domain with ralaniten or an analog such as EPI-7170 causes accumulation of cells in the G1-phase of the cell cycle. Inhibition of cyclin-dependent kinases 4/6 with palbociclib also leads to accumulation of cells in the G1-phase. Here, a combination of EPI-7170 with palbociclib attenuated the in vivo growth of human castration-resistant prostate cancer xenografts that are resistant to antiandrogens. Cell-cycle tracing experiments in cultured cells revealed that EPI-7170 targeted cells in the S-phase, possibly through inducing DNA damage or impairing the DNA damage response, whereas palbociclib targeted the G1–S transition to delay the cell cycle. Combination treatment prevented cells in G1 and G2–M from progressing in the cell cycle and caused a portion of cells in the S-phase to arrest, which contributed to a twofold increase in doubling time to &gt;63 hours compared with 25 hours in control cells. Importantly, sequential combination treatments with palbociclib administered first then followed by EPI-7170, resulted in more cells accumulating in G1 and less cells in the S-phase than concomitant combination which was presumably because each inhibitor has a unique mechanism in modulating the cell cycle in cancer cells. Together, these data support that the combination therapy was more effective than individual monotherapies to reduce tumor growth by targeting different phases of the cell cycle.
Posttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome
Authors: Zanoni Paolo , Panteloglou Grigorios , Othman Alaa , Haas Joel T. , Meier Roger , Rimbert Antoine , Futema Marta , Abou Khalil Yara , Norrelykke Simon F. , Rzepiela Andrzej J. , Stoma Szymon , Stebler Michael , van Dijk Freerk , Wijers Melinde , Wolters Justina C. , Dalila Nawar , Huijkman Nicolette C. A. , Smit Marieke , Gallo Antonio , Carreau Valérie , Philippi Anne , Rabès Jean-Pierre , Boileau Catherine , Visentin Michele , Vonghia Luisa , Weyler Jonas , Francque Sven , Verrijken An , Verhaegen Ann , Van Gaal Luc , van der Graaf Adriaan , van Rosmalen Belle V. , Robert Jerome , Velagapudi Srividya , Yalcinkaya Mustafa , Keel Michaela , Radosavljevic Silvija , Geier Andreas , Tybjaerg-Hansen Anne , Varret Mathilde , Rohrer Lucia , Humphries Steve E. , Staels Bart , van de Sluis Bart , Kuivenhoven Jan Albert , von Eckardstein Arnold 
Published: November 2021

Background:
The LDLR (low-density lipoprotein receptor) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease.

Methods:
We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit genes were validated by in vitro experiments as well as analyses of data sets on gene expression and variants in human populations.

Results:

The knockdown of 54 genes significantly inhibited LDL uptake. Fifteen of them encode for components or interactors of the U2-spliceosome. Knocking down any one of 11 out of 15 genes resulted in the selective retention of intron 3 of
LDLR
. The translated LDLR fragment lacks 88% of the full length LDLR and is detectable neither in nontransfected cells nor in human plasma. The hepatic expression of the intron 3 retention transcript is increased in nonalcoholic fatty liver disease as well as after bariatric surgery. Its expression in blood cells correlates with LDL-cholesterol and age. Single nucleotide polymorphisms and 3 rare variants of one spliceosome gene,
RBM25
, are associated with LDL-cholesterol in the population and familial hypercholesterolemia, respectively. Compared with overexpression of wild-type
RBM25
, overexpression of the 3 rare
RBM25
mutants in Huh-7 cells led to lower LDL uptake.

Conclusions:

We identified a novel mechanism of posttranscriptional regulation of LDLR activity in humans and associations of genetic variants of
RBM25
with LDL-cholesterol levels.
The Ghost Club, 1882–1936
Authors: Luckhurst Roger 
Published: November 2021

AbstractThe Ghost Club was founded to discuss matters spiritual, psychic and occult in 1882 by Spiritualist William Stainton Moses and mystic Alfred Alaric Watts. It was intended as a club ruled by a gentleman’s code of honour—with all matters discussed kept strictly confidential. While maintaining secrecy, it also obsessively minuted and documented its discussions, leaving behind thousands of pages of records that have yet to be properly investigated, owing to conditions around their use. This essay is an attempt to examine the importance of the Club, and how it might readjust our understanding of the networks of the London occult in the late-Victorian and Edwardian eras.
Anna Kingsford and the Intuitive Science of Occultism
Authors: Ferguson Christine 
Published: November 2021

AbstractFeminist, anti-vivisectionist, occultist, and one of the first British women to qualify as a medical doctor, Anna Kingsford remains notably absent from recent studies of Victorian science and spiritualism. Her efforts to synthesize occult and scientific worldviews have been side-lined by those of male contemporaries such as Oliver Lodge and Alfred Russel Wallace, ones whose professional status and gender coordinates more readily align with implicit assumptions about the kind of person for whom disenchantment posed an intellectual problem that might best be solved in the laboratory. My paper positions Kingsford at the very heart of the late Victorian project to accommodate scientific innovation and spiritual belief by tracing her attempts to forge an intuitive epistemology superior to what she viewed as the deeply suspect championship of objectivity. In doing so, it aims to expose and redress blind spots within recent esotericism studies-based approaches to the disenchantment debate.