bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation-sensing catalase-mimicking nanozymes alleviate acute kidney injury via reversing local oxidative stress
Authors: Choi Hong Sang , Mathew Ansuja Pulickal , Uthaman Saji , Vasukutty Arathy , Kim In Jin , Suh Sang Heon , Kim Chang Seong , Ma Seong Kwon , Graham Sontyana Adonijah , Kim Soo Wan , Park In-Kyu , Bae Eun Hui
Published: April 2022

Background

The reactive oxygen species (ROS) and inflammation, a critical contributor to tissue damage, is well-known to be associated with various disease. The kidney is susceptible to hypoxia and vulnerable to ROS. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of chronic kidney disease and finally, end-stage renal disease. Thus, delivering therapeutic agents to the ROS-rich inflammation site and releasing the therapeutic agents is a feasible solution.

Results

We developed a longer-circulating, inflammation-sensing, ROS-scavenging versatile nanoplatform by stably loading catalase-mimicking 1-dodecanethiol stabilized Mn3O4(dMn3O4) nanoparticles inside ROS-sensitive nanomicelles (PTC), resulting in an ROS-sensitive nanozyme (PTC-M). Hydrophobic dMn3O4nanoparticles were loaded inside PTC micelles to prevent premature release during circulation and act as a therapeutic agent by ROS-responsive release of loaded dMn3O4once it reached the inflammation site.

Conclusions

The findings of our study demonstrated the successful attenuation of inflammation and apoptosis in the IRI mice kidneys, suggesting that PTC-M nanozyme could possess promising potential in AKI therapy. This study paves the way for high-performance ROS depletion in treating various inflammation-related diseases.

Graphical Abstract
The prognostic role of tumor size in stage T1 gastric cancer
Authors: Chen Yan , Jia Yukun , Peng Zhan , Wang Guangye
Published: April 2022

Background

The purpose was to assess the contribution of tumor size to the prognosis of patients with gastric cancer.

Methods

Patient data were sourced from the Surveillance, Epidemiology, and End Results program (SEER) database. Cox proportional risk regression was performed to determine the prognostic role of tumor size. Kaplan-Meier curves were conducted to calculate survival curves. Consistency index (c-index) and subject exercise curve (ROC) were utilized to assess the predictive ability of each factor on the prognosis of gastric cancer.

Results

Tumor size is preferable to other widely accepted prognostic clinical features in forecasting the survival of patients with gastric cancer.

Conclusions

The discriminatory ability of tumor size at T1 stage is superior to many other clinical prognostic factors.
Promoting an active choice among physically inactive adults: a randomised web-based four-arm experiment
Authors: Landais Lorraine L. , Damman Olga C. , Jelsma Judith G. M. , Verhagen Evert A. L. M. , Timmermans Danielle R. M.
Published: April 2022

Background

Promoting active (i.e., conscious, autonomous, informed, and value-congruent) choices may improve the effectiveness of physical activity interventions. This web-based four-arm experimental study investigated the effect of promoting an active versus passive choice regarding physical activity on behavioural and psychological outcomes (e.g., physical activity intentions and behaviours, autonomy, commitment) among physically inactive adults.

Methods

Dutch inactive adults were randomized into four groups: physical activity guideline only (control group G), guideline & information (GI), guideline & active choice (GA), or guideline & active choice & action planning (GA +). GA and GA + participants were stimulated to make an active choice by weighing advantages and disadvantages of physical activity, considering personal values, and identifying barriers. GA + participants additionally completed action/coping planning exercises. Passive choice groups G and GI did not receive exercises. Self-reported behavioural outcomes were assessed by a questionnaire pre-intervention (T0, n = 564) and at 2–4 weeks follow-up (T2, n = 493). Psychological outcomes were assessed post-intervention (T1, n = 564) and at follow-up. Regression analyses compared the outcomes of groups GI, GA and GA + with group G. We also conducted sensitivity analyses and a process evaluation.

Results

Although promoting an active choice process (i.e., interventions GA and GA +) did not improve intention (T1) or physical activity (T2 versus T0), GA + participants reported higher commitment at T1 (β = 0.44;95%CI:0.04;0.84) and more frequently perceived an increase in physical activity between T0 and T2 (β = 2.61;95%CI:1.44;7.72). GA participants also made a more active choice at T1 (β = 0.16;95%CI:0.04;0.27). The GA and GA + intervention did not significantly increase the remaining outcomes. GI participants reported higher intention strength (β = 0.64;95%CI:0.15;1.12), autonomy (β = 0.50;95%CI:0.05;0.95), and commitment (β = 0.39;95%CI:0.04;0.74), and made a more active choice at T1 (β = 0.13;95%CI:0.02;0.24). Interestingly, gender and health condition modified the effect on several outcomes. The GA + intervention was somewhat more effective in women. The process evaluation showed that participants varied in how they perceived the intervention.

Conclusions

There is no convincing evidence of a beneficial effect of an active versus passive choice intervention on physical activity intentions and behaviours among inactive adults. Further research should determine whether and how active choice interventions that are gender-sensitized and consider health conditions can effectively increase physical activity.

Trial registration

ClinicalTrials.gov: NCT04973813. Retrospectively registered.
The informal healthcare providers and universal health coverage in low and middle-income countries
Authors: Kumah Emmanuel
Published: April 2022

The World Health Organization has indicated that achieving universal health coverage (UHC) through public sector service delivery alone would not be possible. This calls for corporation, collaboration and partnership between the public and the private sector actors. Informal providers represent a significant portion of the healthcare delivery systems in low-and-middle-income countries (LMCs). However, the presence of this group of private sector actors in national health systems presents both challenges and opportunities. Considering the limited resources in LMCs, ignoring the role of the informal sector in national health systems is not an option. This paper aims to discuss the role of informal health care providers in achieving universal health coverage in low-and-middle-income countries.
Super-critical fluid extract of Bryonopsis laciniosa (Shivlingi) seeds restores fertility in zebrafish models through revival of cytological and anatomical features
Authors: Balkrishna Acharya , Nain Pradeep , Joshi Monali , Kumar Brijesh , Varshney Anurag
Published: April 2022

Background

The Ayurvedic system of medicine mentions the use of seeds of Bryonopsis laciniosa (L.) Naud. (also known as Shivlingi due to their unique structure resembling a ‘Shivling’) for treating sexual dysfunction, impaired fertility, and as a general virility-booster in both males and females. To investigate the scientific basis for such claims, the current study was designed for the chemical characterization of the super critical fluid extracted Shivlingi seed oil (SLSO), and subsequent evaluation of its reproductive fecundity in the zebrafish model of N-ethyl-N-nitrosourea induced infertility.

Results

Linoleic and linolenic acids were the major fatty acids in the SLSO, with trace amounts of β-sitosterol and stigmasterol. Both male and female zebrafish, when fed orally with the SLSO infused pallets, showed a dose-dependent increase in fertility and fecundity rates. Microscopic observations revealed recovery in the gross ovarian anatomy and consequential improvement in egg production in infertile female zebrafish. Similarly, cytological studies exhibited increased sperm counts and motility in male zebrafish. SLSO exhibited effects similar to the human equivalent dose of Letrozole.

Conclusion

Taken together, these observations demonstrated the fertility-boosting potentials of SLSO comparable to the widely used infertility drugs. As a whole, this research work has provided scientific evidence for the rationale behind the use of Shivlingi seeds in Ayurvedic treatment for infertility in humans. Finally, but importantly, this study warrants further scientific investigations into different aspects of SLSO on human reproductive health.
Measuring aniseikonia and investigating neuroplasticity and image factors in amblyopia (MAGNIFY): study protocol for a randomised clinical trial
Authors: South Jayshree , Gao Tina , Calderwood Melinda , Turuwhenua Jason , Roberts Paul , Lee Arier , Collins Andrew , Black Joanna
Published: April 2022

Background

Aniseikonia represents a potential barrier to neuroplasticity which may limit visual outcomes in children with anisometropic amblyopia. Full correction of refractive error is the first step in standard amblyopia treatment, which corrects for image focus but neglects image size differences.

Methods

The MAGNIFY study is a double-masked, randomised clinical trial investigating the effectiveness of aniseikonia correcting lenses in children at first diagnosis of significant anisometropia. We hypothesis that aniseikonia correction lenses will improve image clarity and reduce the retinal size differences producing better visual acuity and stereoacuity improvements after 15 weeks of optical treatment for children with anisometropia. Eligible children will be randomly allocated to the treatment group (aniseikonia-correcting spectacle lenses) or control group (standard spectacle lenses). Visual acuity and binocular functions will be assessed every 5 weeks during the 15-week optical treatment phase according to standard amblyopia treatment protocol.

Discussion

It is possible that correcting aniseikonia along with anisometropia at first diagnosis will promote binocularity as well as increase spectacle adherence by reducing visual discomfort, improving optical treatment outcomes. This could then reduce the need for additional amblyopia treatment such as patching or atropine, reducing the burden on hospital eye departments and potentially improving visual outcomes for children with amblyopia.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000061932. Registered on 24 January 2020. Protocol 15th November 2019, version one.
Fleshy or dry: transcriptome analyses reveal the genetic mechanisms underlying bract development in Ephedra
Authors: Zumajo-Cardona Cecilia , Ambrose Barbara A.
Published: April 2022

Background

Gnetales have a key phylogenetic position in the evolution of seed plants. Among the Gnetales, there is an extraordinary morphological diversity of seeds, the genus Ephedra, in particular, exhibits fleshy, coriaceous or winged (dry) seeds. Despite this striking diversity, its underlying genetic mechanisms remain poorly understood due to the limited studies in gymnosperms. Expanding the genomic and developmental data from gymnosperms contributes to a better understanding of seed evolution and development.

Results

We performed transcriptome analyses on different plant tissues of two Ephedra species with different seed morphologies. Anatomical observations in early developing ovules, show that differences in the seed morphologies are established early in their development. The transcriptomic analyses in dry-seeded Ephedra californica and fleshy-seeded Ephedra antisyphilitica, allowed us to identify the major differences between the differentially expressed genes in these species. We detected several genes known to be involved in fruit ripening as upregulated in the fleshy seed of Ephedra antisyphilitica.

Conclusions

This study allowed us to determine the differentially expressed genes involved in seed development of two Ephedra species. Furthermore, the results of this study of seeds with the enigmatic morphology in Ephedra californica and Ephedra antisyphilitica, allowed us to corroborate the hypothesis which suggest that the extra envelopes covering the seeds of Gnetales are not genetically similar to integument. Our results highlight the importance of carrying out studies on less explored species such as gymnosperms, to gain a better understanding of the evolutionary history of plants.
MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization
Authors: Zhang Yaqi , Le Xi , Zheng Shuo , Zhang Ke , He Jing , Liu Mengting , Tu Chengshu , Rao Wei , Du Hongyuan , Ouyang Yu , Li Changyong , Wu Dongcheng
Published: April 2022

Background

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and a common cause of end-stage renal disease (ESRD). Mesenchymal stem cells (MSCs) possess potent anti-inflammatory and immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage and inflammation.

Methods

This study was designed to determine the protective effects and underlying mechanisms of human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function and histological staining were used to evaluate kidney damage. RNA high-throughput sequencing on rat kidney and UCMSC-derived exosomes was used to identify the critical miRNAs. Co-cultivation of macrophage cell lines and UC-MSCs-derived conditional medium were used to assess the involvement of macrophage polarization signaling.

Results

UC-MSC administration significantly improved renal function, reduced the local and systemic inflammatory cytokine levels, and attenuated inflammatory cell infiltration into the kidney tissue in DN rats. Moreover, UC-MSCs shifted macrophage polarization from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. Mechanistically, miR-146a-5p was significantly downregulated and negatively correlated with renal injury in DN rats as determined through high-throughput RNA sequencing. Importantly, UC-MSCs-derived miR-146a-5p promoted M2 macrophage polarization by inhibiting tumor necrosis factor receptor-associated factor-6 (TRAF6)/signal transducer and activator of transcription (STAT1) signaling pathway. Furthermore, miR-146a-5p modification in UC-MSCs enhanced the efficacy of anti-inflammation and renal function improvement.

Conclusions

Collectively, our findings demonstrate that UC-MSCs-derived miR-146a-5p have the potential to restore renal function in DN rats through facilitating M2 macrophage polarization by targeting TRAF6. This would pave the way for the use of miRNA-modified cell therapy for kidney diseases.
PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy
Authors: Fischer Thomas , Hartmann Oliver , Reissland Michaela , Prieto-Garcia Cristian , Klann Kevin , Pahor Nikolett , Schülein-Völk Christina , Baluapuri Apoorva , Polat Bülent , Abazari Arya , Gerhard-Hartmann Elena , Kopp Hans-Georg , Essmann Frank , Rosenfeldt Mathias , Münch Christian , Flentje Michael , Diefenbacher Markus E.
Published: April 2022

Background

Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy.

Results

We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model.

Conclusion

PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
Pharmacological activation of ATF6 remodels the proteostasis network to rescue pathogenic GABAA receptors
Authors: Wang Meng , Cotter Edmund , Wang Ya-Juan , Fu Xu , Whittsette Angela L. , Lynch Joseph W. , Wiseman R. Luke , Kelly Jeffery W. , Keramidas Angelo , Mu Ting-Wei
Published: April 2022

Background

Genetic variants in the subunits of the gamma-aminobutyric acid type A (GABAA) receptors are implicated in the onset of multiple pathologic conditions including genetic epilepsy. Previous work showed that pathogenic GABAA subunits promote misfolding and inefficient assembly of the GABAA receptors, limiting receptor expression and activity at the plasma membrane. However, GABAA receptors containing variant subunits can retain activity, indicating that enhancing the folding, assembly, and trafficking of these variant receptors offers a potential opportunity to mitigate pathology associated with genetic epilepsy.

Results

Here, we demonstrate that pharmacologically enhancing endoplasmic reticulum (ER) proteostasis using small molecule activators of the ATF6 (Activating Transcription Factor 6) signaling arm of the unfolded protein response (UPR) increases the assembly, trafficking, and surface expression of variant GABAA receptors. These improvements are attributed to ATF6-dependent remodeling of the ER proteostasis environment, which increases protein levels of pro-folding ER proteostasis factors including the ER chaperone BiP (Immunoglobulin Binding Protein) and trafficking receptors, such as LMAN1 (Lectin Mannose-Binding 1) and enhances their interactions with GABAA receptors. Importantly, we further show that pharmacologic ATF6 activators increase the activity of GABAA receptors at the cell surface, revealing the potential for this strategy to restore receptor activity to levels that could mitigate disease pathogenesis.

Conclusions

These results indicate that pharmacologic ATF6 activators offer an opportunity to restore GABAA receptor activity in diseases including genetic epilepsy and point to the potential for similar pharmacologic enhancement of ER proteostasis to improve trafficking of other disease-associated variant ion channels implicated in etiologically-diverse diseases.
Effectiveness of mindfulness-based interventions on well-being and work-related stress in the financial sector: a systematic review and meta-analysis protocol
Authors: Dinesh Tantri Keerthi , Shetty Ankitha , Dhyani Vijay Shree , T.S Shwetha , Dsouza Komal Jenifer
Published: April 2022

Background

Work-related stress is a common phenomenon, often noticed in the employees of the finance sector. It mirrors counter effects on the wellness of employees, their mental well-being, and physical health. Mindfulness-based interventions (MBIs) raise awareness and attention to the present moment experiences by adopting coping skills. It is necessary to promote employee well-being and reduce work-related stress; hence, the need arises to associate between the level of mindfulness, employee well-being, and work-related stress. A systematic review on the effectiveness of MBIs in the finance sector is necessary to facilitate evidence for the future utility to reduce work-related stress and promote employee well-being.

Methods

In this review, randomized controlled trials, non-randomized control trials, cohort, and cross-sectional and case-control studies that assess the effectiveness of MBIs on the employees in the finance sector will be considered. We propose to perform a literature search which will be conducted from the years 2000 to 2021 on CINAHL, Cochrane Library, ProQuest, PubMed, Scopus, and Web of Science. The search terms will include controlled and accessible terms such as mindfulness-based interventions, mindfulness training, workplace, employees, workers, well-being, employee wellness, occupational health, and finance sector. The outcomes will include the effect on employee well-being and reduction in work-related stress. Two researchers will independently conduct the screening and data extraction and assess the risk of bias. Based on the availability of data, a meta-analysis will also be performed. This protocol follows the Preferred Reporting Items for Systematic reviews and Meta-Analysis-Protocol (PRISMA-P) guidelines. “Assessing the Methodological Quality of Systematic Reviews” will be used to assess the quality of this review.

Discussion

The review attempts to methodically analyse the effectiveness of MBIs among finance sector employees. It will foster to facilitate a detailed description and evidence-based overview of the effectiveness of MBIs on improving work-related stress, mindful awareness, and employee wellness and well-being in employees in the finance sector. The current study will provide an evidence base to researchers, academicians, and practitioners in the selection of mindfulness-based therapies for employees in the finance sector.

Systematic review registration

PROSPERO 2021 CRD42021249782
The multivariate analysis of variance as a powerful approach for circular data
Authors: Landler Lukas , Ruxton Graeme D. , Malkemper E. Pascal
Published: April 2022

Background

A broad range of scientific studies involve taking measurements on a circular, rather than linear, scale (often variables related to times or orientations). For linear measures there is a well-established statistical toolkit based on linear modelling to explore the associations between this focal variable and potentially several explanatory factors and covariates. In contrast, statistical testing of circular data is much simpler, often involving either testing whether variation in the focal measurements departs from circular uniformity, or whether a single explanatory factor with two levels is supported.

Methods

We use simulations and example data sets to investigate the usefulness of a MANOVA approach for circular data in comparison to commonly used statistical tests.

Results

Here we demonstrate that a MANOVA approach based on the sines and cosines of the circular data is as powerful as the most-commonly used tests when testing deviation from a uniform distribution, while additionally offering extension to multi-factorial modelling that these conventional circular statistical tests do not.

Conclusions

The herein presented MANOVA approach offers a substantial broadening of the scientific questions that can be addressed statistically using circular data.
Space-to-space very low frequency radio transmission in the magnetosphere using the DSX and Arase satellites
Authors: McCollough James P. , Miyoshi Yoshizumi , Ginet Gregory P. , Johnston William R. , Su Yi-Jiun , Starks Michael J. , Kasahara Yoshiya , Kojima Hirotsugu , Matsuda Shoya , Shinohara Iku , Song Paul , Reinisch Bodo W. , Galkin Ivan A. , Inan Umran S. , Lauben David S. , Linscott Ivan , Ling Alan G. , Allgeier Shawn , Lambour Richard , Schoenberg Jon , Gillespie William , Stelmash Stephen , Roche Kevin , Sinclair Andrew J. , Sanchez Jenny C. , Pedinotti Gregory F. , Langhals Jarred T.
Published: April 2022

Very low frequency (VLF) waves (about 3–30 kHz) in the Earth’s magnetosphere interact strongly with energetic electrons and are a key element in controlling dynamics of the Van Allen radiation belts. Bistatic very low frequency (VLF) transmission experiments have recently been conducted in the magnetosphere using the high-power VLF transmitter on the Air Force Research Laboratory’s Demonstration and Science Experiments (DSX) spacecraft and an electric field receiver onboard the Japan Aerospace Exploration Agency’s Arase (ERG) spacecraft. On 4 September 2019, the spacecraft came within 410 km of each other and were in geomagnetic alignment. During this time, VLF signals were successfully transmitted from DSX to Arase, marking the first successful reception of a space-to-space VLF signal. Arase measurements were consistent with field-aligned propagation as expected from linear cold plasma theory. Details of the transmission event and comparison to VLF propagation model predictions are presented. The capability to directly inject VLF waves into near-Earth space provides a new way to study the dynamics of the radiation belts, ushering in a new era of space experimentation.

Graphical Abstract
Bone bruising severity after anterior cruciate ligament rupture predicts elevation of chemokine MCP-1 associated with osteoarthritis
Authors: Keil Lukas G. , Onuscheck Douglas S. , Pratson Lincoln F. , Kamath Ganesh V. , Creighton Robert A. , Nissman Daniel B. , Pietrosimone Brian G. , Spang Jeffrey T.
Published: April 2022

Purpose

Anterior cruciate ligament rupture is associated with characteristic bone contusions in approximately 80% of patients, and these have been correlated with higher pain scores. Bone bruising may indicate joint damage that increases inflammation and the likelihood of posttraumatic osteoarthritis. We sought to characterize the severity of bone bruising following acute anterior cruciate ligament injury and determine if it correlates with synovial fluid and serum levels of the proinflammatory chemokine monocyte chemoattractant protein-1 associated with posttraumatic osteoarthritis.

Methods

This was a retrospective analysis of data collected prospectively from January 2014 through December 2016. All patients who sustained an acute ligament rupture were evaluated within 15 days of injury, obtained a magnetic resonance imaging study, and underwent bone-patellar-tendon-bone autograft reconstruction were offered enrollment. The overall severity of bone bruising on magnetic resonance imaging was graded (sum of 0–3 grades in 13 sectors of the articular surfaces). Serum and synovial fluid levels of monocyte chemoattractant protein-1 were measured within 14 days of injury, and serum levels were again measured 6 and 12 months following surgery. Separate univariate linear regression models were constructed to determine the association between monocyte chemoattractant protein-1 and bone bruising severity at each time point.

Results

Forty-eight subjects were included in this study. They had a mean age of 21.4 years and were 48% female. Median overall bone bruising severity was 5 (range 0–14). Severity of bone bruising correlated with higher synovial fluid concentrations of monocyte chemoattractant protein-1 preoperatively (R2 = 0.18, p = 0.009) and with serum concentrations at 12 months post-reconstruction (R2 = 0.12, p = 0.04).

Conclusions

The severity of bone bruising following anterior cruciate ligament rupture is associated with higher levels of the proinflammatory cytokine monocyte chemoattractant protein-1 in synovial fluid acutely post-injury and in serum 12-months following anterior cruciate ligament reconstruction. This suggests that severe bone bruising on magnetic resonance imaging after ligament rupture may indicate increased risk for persistent joint inflammation and posttraumatic osteoarthritis.

Level of evidence

III ― retrospective cohort study.
ALK Inhibitors in Patients With ALK Fusion–Positive GI Cancers: An International Data Set and a Molecular Case Series
Authors: Ambrosini Margherita , Del Re Marzia , Manca Paolo , Hendifar Andrew , Drilon Alexander , Harada Guilherme , Ree Anne Hansen , Klempner Samuel , Mælandsmo Gunhild Mari , Flatmark Kjersti , Russnes Hege G. , Cleary James M. , Singh Harshabad , Sottotetti Elisa , Martinetti Antonia , Randon Giovanni , Sartore-Bianchi Andrea , Capone Iolanda , Milione Massimo , Di Bartolomeo Maria , Pietrantonio Filippo
Published: April 2022

PURPOSE

In GI cancers, anaplastic lymphoma kinase ( ALK) rearrangements are extremely less frequent than in non–small-cell lung cancer but may be important to offer personalized strategies of treatment in selected patients. Data about the activity and efficacy of ALK inhibitors (ALKi) in GI cancers are scarce.

MATERIALS AND METHODS

We assembled a clinical and molecular international data set of pretreated patients with metastatic or nonresectable cancers of GI primary tumor origin with documented ALK rearrangement treated with at least one line of ALKi. Measurable disease as per RECIST 1.1 was required for response analysis.

RESULTS

Primary tumor sites were distributed as follows: 5 (38%) pancreas, 3 (23%) right colon, and 1 (8%) for each one of gastric, duodenal, rectal, left colon, and biliary tract sites. Seven patients (54%) were treated with alectinib, 5 (38%) with crizotinib, and 1 (8%) with entrectinib. After disease progression, five patients (38%) received a subsequent ALKi treatment line, and at the time of data cutoff date, treatment was still ongoing in two patients. Five of 12 evaluable patients (41%) achieved a partial response to first-line ALKi, five patients (41%) had stable disease, and 2 (17%) had progressive disease. No complete responses were registered. At a median follow-up of 39.6 months (interquartile range: 19.8-59.5), the median progression-free survival was 5.0 months (95% CI, 3.68 to no response) and the median overall survival was 9.3 months (95% CI, 5.46 to no response).

CONCLUSION

Treatment with ALKi provides remarkable responses and clinical benefit in pretreated patients with ALK fusion–positive GI malignancies. Despite the rarity, ALK rearrangements represent an important therapeutic target in individual pretreated patients with GI solid tumors. Further work providing prospective clinical validation of this target is needed.
The Addicted Self
Authors: Cree Jose
Published: April 2022

This article explores the formation and characterization of early modern addiction through the interactions of mind, body, and will, focusing particularly on the work of the sixteenth-century Christian philosopher Pierre de La Primaudaye. In La Primaudaye’s writings addiction is a wholly internalized behavior, the product of repeated interactions within the mind. Intended for the purpose of cultivating virtuous behaviors, these interactions could become corrupted, resulting in negative addictions formed between overwhelming passions, a clouded judgment, and an inflexible will. The specific types of addiction a person inclined toward were determined by a host of variables, including temperament, age, and gender. As this article reveals, in early modern accounts of addicted behavior young men were associated with lust and old men with contemplation, while women were considered more vulnerable to all addictions, virtuous and sinful. The image of addiction that emerges from this examination is one not of a disease or a disorder, but of a natural function of the body that could on occasion be led astray.
Opium and Logistical Nightmares
Authors: Zieger Susan
Published: April 2022

This essay argues that opium’s pivotal role in nineteenth-century political economy and aesthetics constructed addiction as a relationship between labor and capital that has persisted throughout the twentieth and into the twenty-first century. Nineteenth-century discourses on opium addiction frame it as a crisis of sovereignty for individuals and masses in ways that veil its relationships to labor, collectivity, and community. Yet addiction arises within broad systems as much as it does within individuals: in this exemplary case, of labor, empire, opium, and logistics. This essay rereads nineteenth-century discourses of opium addiction through “the logistical sublime,” in which all manufacturing and distribution processes go smoothly, and “the logistical nightmare,” in which they descend into chaos. It reframes opium addiction as a logistical technique that secured and maintained the preeminence of British, and later, Chinese and US imperial capital.
All Aboard
Authors: Lansky Ellen
Published: April 2022

This essay situates Ernest Hemingway’s iconic “Hills Like White Elephants” as a short story about drinking. From this perspective, Hemingway’s story enables readers to experience a personal and deeply felt emotional engagement with the characters, the scene, and the situation. Moreover, his technique enlists readers as “drinking buddies” and provides an entrée into the culture of alcohol. Despite the macho image that Hemingway himself helped construct and deploy, his work invites women into the scene and, indeed, centralizes a key figure often overlooked in the history of modern American fiction criticism: the drinking woman.
Latest developments and scope of Health Technology Assessment in India: Tapping into the future
Authors: Rajwar Eti , Parsekar Shradha S. , Pundir Prachi , Brand Helmut , Brand Angela
Published: April 2022

Health Technology Assessment (HTA) is a multifaceted approach for informing policy by considering social, medical, economic and ethical aspects in a systematic and transparent manner. HTA is an important tool for decision-making, priority-setting and for resource allocation, leading to Universal Health Coverage (UHC). The importance of HTA becomes more pronounced in developing countries such as India. In this review, we have summarised the status and future scope of HTA in India after referring to the scientific literature available in the form of journal articles and government reports.

HTA supports prioritisation of healthcare services to be included in UHC and the provision of affordable and quality healthcare services in India. India established ‘HTA in India’ (HTAIn) in January 2017 as a starting point in HTA activities and this centre conducts HTA studies of various methodologies upon receiving requests from the different central and state departments. HTA in India is a relatively new concept and the processes are not streamlined compared to countries where HTA is established. Although an HTA manual is present for guiding the HTA process in India, there is lack of clarity on the HTA information considered for translating evidence into policy or practice. Additionally, there is a dearth of individual capacity to undertake high quality HTA in the country.  HTAIn initiative showcases India’s political commitment towards achieving UHC and for HTA. However, there is an imminent need to expand the role of the technical partners and regional resource hubs in capacity building in HTA by involving the private sector in HTA processes.
Factors affecting access to health services by older adults in an urban community in Thailand: a cross-sectional study
Authors: Jirathananuwat Areeya
Published: April 2022

Background: The impending rapid change in Thailand’s older population has many important implications for health policy, especially older adults’ health problems, which are major cause of  them accessing health services. This study aimed to study factors affecting access to health services for older adults in urban communities in Thailand, as well as performing a situational survey of health service utilization.

Methods: This cross-sectional study included 886 older adults from four types of urban communities (slum, city, suburban, and community building). Data were collected using an interview questionnaire. Information about health service variables were extracted and followed the five dimensions of accessibility by Penchansky & Thomas: availability, accessibility, accommodation, affordability and acceptability. Data were analyzed using percentage mean and standard deviation (SD). Analysis of factors affecting access to health service was performed using Logistic regression.

Results: The utilization of health services was high among five dimensions. They were composed of availability (mean 4.2, SD.=0.59), accessibility (mean 4.1, SD.=0.69), accommodation (mean 3.9, SD.=0.67), affordability (mean 4.2, SD.= 0.62), and acceptability (mean 4.1, SD.=0.62). A summary of all dimensions revealed a mean of 4.1 (SD.= 0.52). Factors affecting older adults access to health services were using health insurance rights for health care service, and concern about the necessity of health care.

Conclusions: Encouraging older adults to change their health insurance rights to the nearest hospital and promoting the provision of holistic health information, which will support older adults in accessing more health services to improve their health outcomes.
A multi-spectral myelin annotation tool for machine learning based myelin quantification
Authors: Çapar Abdulkerim , Çimen Sibel , Aladağ Zeynep , Ekinci Dursun Ali , Ayten Umut Engin , Kerman Bilal Ersen , Töreyin Behçet Uğur
Published: April 2022

Myelin is an essential component of the nervous system and myelin damage causes demyelination diseases. Myelin is a sheet of oligodendrocyte membrane wrapped around the neuronal axon. In the fluorescent images, experts manually identify myelin by co-localization of oligodendrocyte and axonal membranes that fit certain shape and size criteria. Because myelin wriggles along x-y-z axes, machine learning is ideal for its segmentation. However, machine-learning methods, especially convolutional neural networks (CNNs), require a high number of annotated images, which necessitate expert labor. To facilitate myelin annotation, we developed a workflow and software for myelin ground truth extraction from multi-spectral fluorescent images. Additionally,  to the best of our knowledge, for the first time, a set of annotated myelin ground truths for machine learning applications were shared with the community.
3D metal powder mixing
Authors: Talati Jigar
Published: April 2022

Jigar Talati, founder of Hexagon Product Development Pvt Ltd, discusses the benefits of 3D blenders to ensure a homogeneous metal powder mix.
Why the construction materials shortage will make the use of composites mainstream
Authors: Burns Stuart
Published: April 2022

Stuart Burns, managing director of Dura Composites, discusses how composites could help construction companies currently suffering from a shortage of materials.
How AI-based biometrics can guarantee e-signature security
Authors: Sahib Mo
Published: April 2022

E-signatures are increasingly being used in online business, but they still present security risks. Mo Sahib of Borderless Security and FilesDNA explains how the latest intelligent biometric systems can solve this.
Control Inhibitorio y Regulación emocional: características, diferencias y desarrollo en la etapa preescolar
Authors: Donovan Clara
Published: April 2022

El presente artículo de revisión bibliográfica investiga la relación entre los conceptos de regulación emocional y control inhibitorio destacando sus funciones y diferencias. A su vez, se mencionan sus características principales en la etapa preescolar. Se ha realizado una revisión exhaustiva y minuciosa sobre el tema en las principales fuentes de información  y se ha llegado a la conclusión de que son constructos diferentes pero a su vez interdependientes. Mantienen una relación estrecha y recíproca compartiendo importantes puntos de desarrollo en común. El control inhibitorio es una de las principales funciones ejecutivas, junto con la memoria de trabajo y la flexibilidad cognitiva, y todas ellas se encuentran en la base de cualquier conducta organizada. Por otro lado, permiten el desarrollo de otras funciones más complejas como pueden ser el razonamiento, la planificación o la capacidad para resolver problemas. Estas habilidades de alto nivel cognitivo se desarrollan y evolucionan a lo largo de la vida manifestando un importante desarrollo en la etapa preescolar. Resultan imprescindibles para lograr una adaptación exitosa al ambiente, mantener una salud integral y están directamente vinculadas a la adquisición y desarrollo de las habilidades socioemocionales. En la infancia, tanto el control inhibitorio como la regulación emocional resultan fundamentales para obtener éxito académico y responder adecuadamente a las exigencias del entorno. El primero permite regular la atención, la cognición y el comportamiento mientras que la regulación emocional posibilita que las personas aprendan a regular la intensidad y la expresión de sus emociones. Ambos constructos están fuertemente vinculados con el desarrollo de competencias socioemocionales que promoverán interacciones sociales positivas y significativas. El control inhibitorio se encuentra en la base del proceso regulatorio de emociones y ambas habilidades tienen un importante desarrollo durante la etapa preescolar. Se pueden entrenar y, por lo tanto, se deben contemplar en las propuestas educativas.
La educación musical: fundamentos y aportaciones a la neuroeducación.
Authors: Oriola Requena Salvador , Gustems Carnicer Josep , Navarro Calafell Mercè
Published: April 2022

La música es un potente activador cerebral que implica a una extensa red de estructura neurales corticales, subcorticales y del oído interno para su procesamiento. Estas estructuras no solo intervienen en la práctica musical, sino que también son específicas de otras funciones como la memoria, la emoción o el razonamiento matemático. Por esta razón, la educación musical puede repercutir positivamente no solo en el aprendizaje de un arte en sí mismo como es la música sino también en el desarrollo de competencias clave como la matemática, la lingüística, la interpersonal, etc. El presente artículo es una revisión bibliográfica de tipo multidisciplinar cuyo objetivo es conocer cómo funciona el cerebro musical y cómo la música puede contribuir al desarrollo competencial tanto artístico-cultural como de otras competencias. A partir de dicha revisión se puede concluir que la música puede usarse como un recurso neuroeducativo eficaz para entrenar el cerebro de forma holística y mejorar la interconexión neuronal, lo cual puede beneficiar la formación integral de las personas, así como su bienestar, tanto personal como social. Aun así, cabe seguir indagando sobre la neuroarquitectura musical y su contribución a las neurociencias para conocer con exactitud cómo aprende el cerebro y la importancia de la música como recurso educativo.
Criterion to determine the wave vector range of heterodyne near-field
exposure time-dependent spectrum
Authors: Peng Yi , Qiu Jian , Peng Li , Luo Kaiqing , Liu Dongmei , Han Peng
Published: April 2022

Recently, image methods for measuring dynamics of nanoparticles have garnered
attention; however, the low-speed frame rate of normal image sensors
limits their application. Applying a low-speed detector can extract
fast dynamic information by the method of an exposure time-dependent
spectrum, whereas its accuracy is too sensitive to the wave vector
range selection. In this paper, we present a criterion to determine
the wave vector range for the image method of heterodyne near-field
light scattering, where the hologram of the particles is analyzed to
extract the particle dynamics. A normalized instrument factor ratio

𝓇
(
q
)

is defined, and the accuracy of
results can be guaranteed when the upper limit

q

up

is selected at the maximum of

𝓇
(

q

up

)
=
1

, and the lower limit

q

low

is selected according to the optimal
goodness of fit

R
2

. The experimental results verify the
effectiveness of the proposed criterion. Since most image methods for
nanoparticle characterizing are related to the wave vector range
selection, it is believed that the idea of this criterion can be
extended generally.
Secrecy performance analysis for a NOMA based FSO-RF system with imperfect CSI
Authors: Zhuang Yongzhi , Zhang Jiliang
Published: April 2022

In this paper, we consider a non-orthogonal multiple access (NOMA) based mixed free space optical–radio frequency (FSO-RF) system with imperfect channel state information (CSI) and evaluate the secrecy performance in terms of secrecy outage probability (SOP). Specifically, a source (

S

) first forwards an optical NOMA signal to a relay (

R

) via an FSO link, and then

R

performs an optical–electrical conversion and broadcasts the converted signal to users over the RF links. Both the FSO and RF links are incorporated with the NOMA technique, and the CSI imperfection in both links is considered. Assuming both users have multiple antennas, and adopting the maximal ratio combining diversity schemes, we derive the analytical and asymptotic expressions for SOP when the FSO link undergoes gamma–gamma fading with pointing error and the RF links are subject to Rayleigh fading. In addition, both decode-and-forward and amplify-and-forward protocols are taken into account and compared. Monte Carlo simulations are also used to verify the accuracy of the derived results.
Ray tracing in concentric gradient-index media: optical Binet equation
Authors: Liu Wanguo
Published: April 2022

The Binet equation in mechanics describes the orbital geometry of a moving particle under a central force field. In this paper, as its counterpart in optics, we show this formula can be similarly utilized in ray tracing of a gradient-index (GRIN) medium with a concentric field. As an inference of Fermat’s principle, this generalization is called the optical Binet equation (OBE). A remarkable advantage of OBE is that it can not only determine the ray trace or concentric GRIN field once one of them is given, but also derive the propagation time inside the medium. As examples, we apply OBE to rays passing through a Maxwell fish-eye lens, Luneburg lens, Eaton lens, concentrator, and hyperbolic deflector, the time delay of which can be calculated once the GRIN field or ray trace equation is solved. The results are well matched with simulations, proving it to be an effective tool in solving problems of the concentric GRIN field.
DNA sequencing by Förster resonant energy transfer
Authors: Fotouhi Bashir , Faramarzi Vahid , Ahmadi Vahid
Published: April 2022

We propose a new DNA sequencing concept based on nonradiative Förster resonant energy transfer (FRET) from a donor quantum dot (QD) to an acceptor molecule. The FRET mechanism combined with the nanopore-based DNA translocation is suggested as a novel concept for sequencing DNA molecules. A recently-developed hybrid quantum/classical method is employed, which uses time-dependent density functional theory and quasistatic finite difference time domain calculations. Due to the significant absorbance of DNA bases for photon energies higher than 4 eV, biocompatibility, and stability, we use Zinc-Oxide (ZnO) QD as a donor in the FRET mechanism. The most sensitivity for the proposed method to DNA is achieved for the Hoechst fluorescent-dye acceptor and 1 nm ZnO-QD. Results show that the insertion of each type of DNA nucleobases between the donor and acceptor changes the frequency of the emitted light from the acceptor molecule between 0.25 to 1.6 eV. The noise analysis shows that the method can determine any unknown DNA nucleobases if the signal-to-noise ratio is larger than 5 dB. The proposed concept and excellent results shed light on a new promising class of DNA sequencers.
High-precision lithography thick-mask model based on a decomposition machine learning method
Authors: Li Ziqi , Dong Lisong , Jing Xuyu , Ma Xu , Wei Yayi
Published: April 2022

The thick-mask model had been used to simulate the diffraction behavior of the three-dimensional photomask in optical lithography system. By exploring the edge interference effect that appears in the diffraction near-field (DNF), an improved thick-mask model with high precision is proposed. The diffraction transfer matrix (DTM) is introduced to represent the transformation from the layout pattern to the corresponding DNF. In this method, the DTM is learned from a training library including the rigorous DNF of some representative mask clips. Given a thick-mask pattern, it is firstly decomposed into a set of segments around the sampling points at corners and edges. Then, the local DNF of each segment is calculated based on the corresponding DTM. Finally, all the local DNF segments are synthesized together to simulate the entire thick-mask DNF. The results show that the proposed method can significantly improve the simulation accuracy compared to the traditional filter-based method, meanwhile retaining a high computation speed.