bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Clinical Trials in Africa—An Untapped Opportunity: Recommendations From AORTIC 2019 Conference Special Interest Group in Clinical Trials
Authors: Ibraheem Abiola , Pillai Colin , Okoye Ifeoma , Smith J. Joshua , Reidy-Lagunes Diane , Macaulay Grace , Alatise Olusegun
Published: September 2021

Cancer is now a formidable health care burden in sub-Saharan Africa (SSA) due to lifestyle westernization and longer life expectancy. The exponential increase in cancer incidence coupled with high mortality rate is not comparable with that seen in westernized countries. To address global cancer disparity, globalization of cancer clinical trials to involve sub-Saharan Africa can serve as a platform where innovative targeted therapies can be made available to patients in the environ. In the 2019 African Organization for Research and Training in Cancer (AORTIC) conference held at Maputo, Mozambique, a group of clinical trialists spanning across multiple continents highlighted the opportunities in Africa for the conduct of cancer clinical trials. The secondary purpose of the meeting was to address the belief that Africa was incapable of conducting interventional cancer trials but showed the in-continent strengths, such as available capacities, trained local clinical trialists with clinical trial experiences, clinical trial consortia, local capabilities, mapping out logistics, ethical consideration, political will, real-time benefits of clinical trials to clinical practice, and future directions for trials.
Player Tracking Technology and Data for Injury Prevention in the National Football League
Authors: Ghasem Wesley , Valenzuela Joshua , Saxon Leslie A.
Published: September 2021

The recent partnership of NFL’s Next Gen Stats with Amazon Web Services has created a buzz among media and fans, yet the full scope and utility of digital biosensors has yet to be determined. We review current uses of Global Positioning System technology and digital biosensors in the NFL and discuss the future role of this technology in injury prevention. A complete literature review was conducted, along with review of the NFL web site and news outlet articles, to obtain a comprehensive assessment of all prior and current uses of biosensor technology in the NFL. Limited data exist on successful injury prevention and return to play, and utilization of this emerging technology has mostly been for fan experience. While ethical and legal challenges exist, the integration of digital biosensor and GPS technology in the NFL has enormous potential and is an invaluable tool in the comprehensive assessment of player health.
The Application Value of Magnetic Resonance Imaging (MRI)in the Clinical Diagnosis in Hospital Management
Authors: Chen Yan , Zhou Hong-Mei , Jiang Qijie
Published: September 2021

Background & Objective:  To evaluate the application value of dynamic enhanced magnetic resonance imaging (DCE-MRI) in the clinical diagnosis in hospital based on the fuzzy C-means clustering algorithm and conduct its cost-benefit analysis in practice.

Methods: This study was conducted from October 11th 2020 to November 25, 2020. Eighteen patients with lung cancer confirmed by pathology were collected and examined by DCE-MRI one day before and one month after surgery using a fuzzy C-means clustering algorithm. And then, taking Guang’an District People’s Hospital as an example, the present paper conducts the cost-benefit analysis with the utilization of net present value (NPV).

Results: After 1-month review, eleven patients with effective treatment, four numerical Ktrans, Kep, Ve, Vp compared with preoperative decreased, which Ktrans, Kep, the change of the Ve was statistically significant (P < 0.05), the Vp of decline has no statistical significance (P > 0.05), the experimental and ineffective group after an operation, compared to four numerical Ktrans and Vp difference was statistically significant (P < 0.05), the corresponding AUC (area under the curve) to 1 and 0.818, the sensitivity of 100% and 85.7%, a specific degree of 100% and 72.7%. The NPV analysis results showed that the hospital could achieve profit and loss balance in the third year after purchasing MRI equipment and then gradually obtain positive cash inflow.

Conclusion: The application of MRI in the Clinical Diagnosis helps hospital promote the therapeutic effect, thus having great practical value, and also contributes to increasing benefits in the long run.

Abbreviations: DCE-MRI: Dynamic enhanced magnetic resonance imaging. NPV: Net Present Value. RECIST: Reliable Tumor Evaluation Criteria. CR: Complete Response.

doi: https://doi.org/10.12669/pjms.37.6-WIT.4791

How to cite this:Chen Y, Zhou HM, Jiang QJ. The Application Value of Magnetic Resonance Imaging (MRI) in the Clinical Diagnosis in Hospital Management. Pak J Med Sci. 2021;37(6):1710-1713.   doi: https://doi.org/10.12669/pjms.37.6-WIT.4791

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Diagnosis and analysis of primary central nervous system lymphoma based on MRI segmentation algorithm
Authors: Lu Guanping , Li Ying , Liang Xinqiang , Zhao Zhengjun
Published: September 2021

Objective: This paper summarizes the MRI imaging findings of primary central nervous system lymphoma (PCNSL) in the posterior cranial fossa to improve the accuracy of PCNSL diagnosis in the posterior cranial fossa.

Methods: This study retrospectively analyzed the MRI imaging manifestations of 15 PCNSL posterior cranial fossa cases confirmed by puncture or surgical pathology from June 2017 to May 2018, including their occurrence sites, the number of lesions, MRI plain and enhanced manifestations, and diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy. Imaging (MRS) performance.

Results: A total of 15 cases were enrolled, including 10 cases of single lesion and five cases of multiple lesions. The total number of lesions was 25, which were in the cerebellar hemisphere and cerebellar vermis, midbrain, fourth ventricle, and pontine cerebellum. The lesions were round, irregular, nodular, patchy, with low or medium signals on T1WI, equal or slightly higher signals on T2WI, and enhanced with 25 meningiomas-like gray matter signals. All of them were significantly strengthened. “Acupoint sign” and “umbilical depression sign” were seen in eight lesions. There were 17 massive and nodular enhancements, four striped enhancements, three patchy enhancements, and one circular enhancement. five cases of DWI showed homogeneous high signal, two cases showed uneven high signal, and 3 cases showed medium signal. The ADC value of tumor parenchyma in 10 patients was (0.62±0.095)×10-3mm2/s. MRS examination showed obvious Lip peak in two cases.

Conclusion: PCNSL in posterior cranial fossa has certain characteristics. DWI, ADC value and MRS are helpful to improve the correct diagnosis rate of PCNSL.

doi: https://doi.org/10.12669/pjms.37.6-WIT.4843

How to cite this:Lu G, Li Y, Liang X, Zhao Z. Diagnosis and analysis of primary central nervous system lymphoma based on MRI segmentation algorithm. Pak J Med Sci. 2021;37(6):1585-1589. doi: https://doi.org/10.12669/pjms.37.6-WIT.4843

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Adjunctive postoperative course of dexamethasone in chronic subdural hematoma: Effect on surgical outcome
Authors: Tariq Jibran , Bhatti Sajid Nazir
Published: September 2021

Objectives: To compare the effect of burrhole craniostomy with and without a postoperative course of dexamethasone on recurrence rate of chronic subdural hematoma (CSDH).

Methods: The study was conducted at the Department of Neurosurgery, Pakistan Institute of Medical Sciences, Islamabad, from September 2017 till May 2018. Adult patients diagnosed with CSDH and advised burrhole craniostomy were enrolled in this prospective randomized controlled trial. Participants were randomized into Group-1 (receiving two weeks dexamethasone), and Group-2 (no dexamethasone). Clinical assessment and Brain CT were done preoperatively, second postoperative day, sixth and twelfth postoperative week, with outcome assessed at twelfth postoperative week. Complications of treatment and recurrence rate were recorded.

Results: Ninety-two (n=92, 46 in each group) patients were enrolled. Improvement in neurological (95.7% vs 93.5%; P=0.646) and radiological outcome (95.7% vs 93.5%; P=0.646) was similar in both groups. Complication rate was higher in Group-1 but not significantly different (58.7% vs 43.5%; P=0.535). Most frequent complication was pneumocephalus, with mortality rate equal (n=one). Recurrence was observed in 2.2% (n=1/46) patients in Group-1 and 4.3% (n=2/46) in Group-2 (P=0.557), which was not statistically significant.

Conclusions: Neurological and radiological outcome, and mortality rates were similar in both groups. The recurrence rate was lower and complications slightly higher in Group-1 but these were not statistically significant.

doi: https://doi.org/10.12669/pjms.37.7.3374

How to cite this:Tariq J, Bhatti SN. Adjunctive postoperative course of dexamethasone in chronic subdural hematoma: Effect on surgical outcome. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.3374

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lymphopenia: A useful predictor of COVID-19 disease severity and mortality
Authors: Toori Kaleem Ullah , Qureshi Muhammad Arsalan , Chaudhry Asma
Published: September 2021

Objective: To detect association of lymphopenia with disease severity and mortality.

Methods: Total 874 COVID RT-PCR positive patients admitted to KRL Hospital Islamabad from April 2020 to August 2020 were included in this cross-sectional study. Lymphopenia was defined as <1100 cells/micro–L. WHO categories for disease severity were used. Demographic profile, absolute lymphocyte counts and co-morbidities were recorded. Pearson’s Chi Square test was used to see association between lymphopenia and disease severity as well as disease outcome. Regression analysis was used to see whether lymphopenia would predict disease severity. Comparison of means of absolute lymphocyte count in different disease categories was done by ANOVA. Tukey’s test range was then used to find the means different from each other. P-value ≤ 0.05 was considered statistically significant

Results: The mean age of patients was 40±12.3 years. Majority patients (73.9%) were asymptomatic. Lymphopenia was present in 6.9% of total patients. Significant association was found between lymphopenia and disease severity as well as lymphopenia and mortality (< 0.001). Lymphopenia was found to be a predictor of disease severity using regression analysis (< 0.001). Comparison of mean absolute lymphocyte count was significant among disease severity categories (< 0.001). On post-hoc analysis, difference in absolute lymphocyte count was significant moving from asymptomatic to mild and then moderate disease category. However no significant difference was seen in absolute lymphocyte count between moderate and severe categories.

Conclusion: Results are compatible with worldwide studies and lymphopenia is valid as a marker of disease severity and mortality

doi: https://doi.org/10.12669/pjms.37.7.4085

How to cite this:Toori KU, Qureshi MA, Chaudhry A. Lymphopenia: A useful predictor of COVID-19 disease severity and mortality. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4085

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effects of HBeAg Status on cellular immune function of patients with Hepatitis B virus/Treponema Pallidum Co-infection
Authors: Luo Wei , Xin Hanxiao , Zhao Pengyun , Jiang Shasha
Published: September 2021

Objectives: This study was aimed at exploring the effects of hepatitis B envelope antigen (HBeAg) status on the cellular immune function of patients with hepatitis B virus/treponema pallidum (HBV/TP) co-infection.

Methods: The clinical data of 79 patients with HBV/TP co-infection admitted to our hospital from January 2019 to January 2020 were retrospectively analyzed. These patients were divided into two groups according to the different HBeAg statuses before the treatment: 41 HBeAg+ patients were included in the HBeAg+ group, while 38 HBeAg- patients were included in the HBeAg- group. The levels of HBV-DNA, T lymphocyte subsets represented by NK cells and cytokines associated with T cells in the peripheral blood (PB) of the patients were compared between both groups.

Results: The HBV-DNA levels in the HBeAg+ group were significantly higher than those in the HBeAg- group (P < 0.05). The levels of CD3+, CD4+, CD4+/CD8+ and natural killer (NK) cells in the HBeAg+ group were higher than those in the HBeAg- group (P < 0.05), while the levels of CD8+ cells were lower than those in the HBeAg- group (P < 0.05). Moreover, the levels of interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-β (TGF-β) in the HBeAg+ group were all significantly higher than those in the HBeAg- group (P < 0.05), but there was no significant difference in the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) between the HBeAg+ group and the HBeAg- group (P > 0.05).

Conclusion: HBeAg+ can increase the HBV-DNA levels in the PB of patients with HBV/TP co-infection, in turn triggering the body to initiate cellular immunity, increasing the levels of T lymphocyte subsets, and promote the secretion of cytokines.

doi: https://doi.org/10.12669/pjms.37.7.4253

How to cite this:Luo W, Xin H, Zhao P, Jiang S. Effects of HBeAg Status on cellular immune function of patients with Hepatitis B virus/Treponema Pallidum Co-infection. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4253

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Metabolomics datasets in the Born in Bradford cohort
Authors: Taylor Kurt , McBride Nancy , J Goulding Neil , Burrows Kimberley , Mason Dan , Pembrey Lucy , Yang Tiffany , Azad Rafaq , Wright John , A Lawlor Deborah
Published: September 2021

Metabolomics is the quantification of small molecules, commonly known as metabolites. Collectively, these metabolites and their interactions within a biological system are known as the metabolome. The metabolome is a unique area of study, capturing influences from both genotype and environment. The availability of high-throughput technologies for quantifying large numbers of metabolites, as well as lipids and lipoprotein particles, has enabled detailed investigation of human metabolism in large-scale epidemiological studies. The Born in Bradford (BiB) cohort includes 12,453 women who experienced 13,776 pregnancies recruited between 2007-2011, their partners and their offspring. In this data note, we describe the metabolomic data available in BiB, profiled during pregnancy, in cord blood and during early life in the offspring. These include two platforms of metabolomic profiling: nuclear magnetic resonance and mass spectrometry. The maternal measures, taken at 26-28 weeks’ gestation, can provide insight into the metabolome during pregnancy and how it relates to maternal and offspring health. The offspring cord blood measurements provide information on the fetal metabolome. These measures, alongside maternal pregnancy measures, can be used to explore how they may influence outcomes. The infant measures (taken around ages 12 and 24 months) provide a snapshot of the early life metabolome during a key phase of nutrition, environmental exposures, growth, and development. These metabolomic data can be examined alongside the BiB cohorts’ extensive phenotype data from questionnaires, medical, educational and social record linkage, and other ‘omics data.
Predicting Human Discretion to Adjust Algorithmic Prescription: A Large-Scale Field Experiment in Warehouse Operations
Authors: Sun Jiankun , Zhang Dennis J. , Hu Haoyuan , Van Mieghem Jan A.
Published: September 2021

Conventional optimization algorithms that prescribe order packing instructions (which items to pack in which sequence in which box) focus on box volume utilization yet tend to overlook human behavioral deviations. We observe that packing workers at the warehouses of the Alibaba Group deviate from algorithmic prescriptions for 5.8% of packages, and these deviations increase packing time and reduce operational efficiency. We posit two mechanisms and demonstrate that they result in two types of deviations: (1) information deviations stem from workers having more information and in turn better solutions than the algorithm; and (2) complexity deviations result from workers’ aversion, inability, or discretion to precisely implement algorithmic prescriptions. We propose a new “human-centric bin packing algorithm” that anticipates and incorporates human deviations to reduce deviations and improve performance. It predicts when workers are more likely to switch to larger boxes using machine learning techniques and then proactively adjusts the algorithmic prescriptions of those “targeted packages.” We conducted a large-scale randomized field experiment with the Alibaba Group. Orders were randomly assigned to either the new algorithm (treatment group) or Alibaba’s original algorithm (control group). Our field experiment results show that our new algorithm lowers the rate of switching to larger boxes from 29.5% to 23.8% for targeted packages and reduces the average packing time of targeted packages by 4.5%. This idea of incorporating human deviations to improve optimization algorithms could also be generalized to other processes in logistics and operations.

This paper was accepted by Charles Corbett, operations management.
Effects of lidar and radar resolution on DNN-based vehicle detection
Authors: Orr Itai , Damari Harel , Halachmi Meir , Raifel Mark , Twizer Kfir , Cohen Moshik , Zalevsky Zeev
Published: September 2021

Vehicle detection plays a critical role in autonomous driving, where two central sensing modalities are lidar and radar. Although many deep neural network (DNN)-based methods have been proposed to solve this task, a systematic and methodological examination on the influence of the data on those methods is still missing. In this work, we examine the effects of resolution on the performance of vehicle detection for both lidar and radar sensors. We propose subsampling methods that can improve the performance and efficiency of DNN-based solutions and offer an alternative approach to traditional sensor-design trade-offs.
Alignment tolerance analysis for divided-pulse nonlinear compression
Authors: Jenkins G. W. , Feng C. , Bromage J.
Published: September 2021

We present an analytic model that describes the output pulse after
Kerr-based spectral broadening with divided-pulse nonlinear
compression that includes errors in unequal pulse division,
birefringent plate retardance, and thermal drift. The model shows that
alignment tolerances become impractically tight at high levels of
nonlinearity and that the angle of incidence on the birefringent
plates can be utilized as a compensator to loosen those tolerances. We
present experimental verification of the model, which is expected to
be a fast and flexible tool to design future divided-pulse nonlinear
compression systems.
Non-back-reflecting polygon scanner with applications in surface cleaning
Authors: Hoang Ha-My , Choi Soojin , Park ChangKyoo , Choi Jiyeon , Ahn Sang Hoon , Noh JiWhan
Published: September 2021

Polygon mirror scanners are attracting considerable interest owing to their rapid speed and large scanning area. Here, we focused on the back-reflection effect of the polygon scanner. A new polygon scanner system was designed based on a geometric analysis. The final equations for the design express the position of the laser beam source having the largest scanning length without the reflected beam traveling back to the fiber. The proposed system performed a raster scan on an area. Additionally, a paint stripping experiment was conducted to demonstrate the potential use of our scanner in commercial laser cleaning applications.
Dynamic non-line-of-sight imaging system based on the optimization of point spread functions
Authors: Pei Chengquan , Zhang Anke , Deng Yue , Xu Feihu , Wu Jiamin , Li David U-Lei , Qiao Hui , Fang Lu , Dai Qionghai
Published: September 2021

Non-line-of-sight (NLOS) imaging reveals hidden objects reflected from diffusing surfaces or behind scattering media. NLOS reconstruction is usually achieved by computational deconvolution of time-resolved transient data from a scanning single-photon avalanche diode (SPAD) detection system. However, using such a system requires a lengthy acquisition, impossible for capturing dynamic NLOS scenes. We propose to use a novel SPAD array and an optimization-based computational method to achieve NLOS reconstruction of 20 frames per second (fps). The imaging system's high efficiency drastically reduces the acquisition time for each frame. The forward projection optimization method robustly reconstructs NLOS scenes from low SNR data collected by the SPAD array. Experiments were conducted over a wide range of dynamic scenes in comparison with confocal and phase-field methods. Under the same exposure time, the proposed algorithm shows superior performances among state-of-the-art methods. To better analyze and validate our system, we also used simulated scenes to validate the advantages through quantitative benchmarks such as PSNR, SSIM and total variation analysis. Our system is anticipated to have the potential to achieve video-rate NLOS imaging.
Direct bandwidth measurement of multimode waveguides based on an optical sampling technique
Authors: Shi Ying , Xu Bingxin , Ma Lin , Xiong Junjie , Fan Xinyu , Zhuang Yudi , He Zuyuan
Published: September 2021

We demonstrate direct bandwidth measurement of 11-cm-long multimode polymer waveguides based on an optical sampling technique for the first time, to our knowledge. The pulse shape can be recovered after transmission due to the advantages such as high bandwidth and high refresh rate of optical sampling technology. A reduction in averaged bandwidth (bandwidth-length product) from 241 GHz (27 GHz·m) to 180 GHz (20 GHz·m) of straight waveguides is observed when using mode scramblers to fully stimulate the higher-order modes. The effects such as bending and crossing structure of the waveguides on the bandwidth are also investigated. The proposed method is effective for measuring the bandwidth and dispersion of meter- and centimeter-long waveguides, fibers, and optical devices.
Investigation of ablation efficiency during the pulsed laser ablation of a zinc metal target in a distilled water environment
Authors: Khodaverdi Mohammad Rasoul , Irani Elnaz
Published: September 2021

In this study, the effect of Nd:YAG laser energy with a 9 ns time duration as one of the important parameters on the laser ablation of a zinc metal target in a distilled water environment has been investigated both experimentally and theoretically. The influence of plasma shielding on the ablation rate for 100–600 mJ energies is also considered. After investigating XRD, SEM, and UV-Vis results of each sample, it is determined that synthesized nanostructures are ZnO nanoparticles, and also the morphologies of the synthesized nanostructures are formed in two forms of hexagonal crystals and amorphous nanosheets. By increasing the laser energy to 400 mJ, the ablation rate on the zinc target increases. However, with increasing energy up to 600 mJ, the plasma shielding effect is evident and the ablation rate is reduced. Also, the theoretical two-fluid heat transfer model of nanosecond pulsed laser ablation is developed to visualize the evolution of temperature distributions, crater profile, and ablation depth.
Evaluating the effectiveness of ensemble voting in improving the accuracy of consensus signals produced by various DTWA algorithms from step-current signals generated during nanopore sequencing
Authors: Smith Michael , Chan Rachel , Khurram Maaz , Gordon Paul M. K.
Published: September 2021

Nanopore sequencing device analysis systems simultaneously generate multiple picoamperage current signals representing the passage of DNA or RNA nucleotides ratcheted through a biomolecule nanopore array by motor proteins. Squiggles are a noisy and time-distorted representation of an underlying nucleotide sequence, “gold standard model”, due to experimental and algorithmic artefacts. Other research fields use dynamic time warped-space averaging(DTWA)algorithms to produce a consensus signal from multiple time-warped sources while preserving key features distorted by standard, linear-averaging approaches. We compared the ability ofDTWBarycentre averaging (DBA), minimize mean (MM) and stochastic sub-gradient descent (SSG) DTWAalgorithms to generate a consensus signal from squiggle-space ensembles of RNA moleculesEnolase,Sequin R1-71-1andSequin R2-55-3without knowledge of their associated gold standard model. We propose techniques to identify the leader and distorted squiggle features prior toDTWAconsensus generation. New visualization and warping-path metrics are introduced to compare consensus signals and the best estimate of the “true” consensus, the study’s gold standard model. TheDBAconsensus was the best match to the gold standard for bothSequinstudies but was outperformed in theEnolasestudy. Given an underlying common characteristic across a squiggle ensemble, we objectively evaluate a novel “voting scheme” that improves the local similarity between the consensus signal and a given fraction of the squiggle ensemble. While the gold standard is not used during voting, the increase in the match of the final voted-on consensus to the underlyingEnolaseandSequingold standard sequences provides an indirect success measure for the proposed voting procedure in two ways: First is the decreased least squares warped distance between the final consensus and the gold model, and second, the voting generates a final consensus length closer to the known underlying RNA biomolecule length. The results suggest considerable potential in marrying squiggle analysis andvoted-on DTWAconsensus signals to provide low-noise, low-distortion signals. This will lead to improved accuracy in detecting nucleotides and their deviation model due to chemical modifications (a.k.a. epigenetic information). The proposed combination of ensemble voting andDTWAhas application in other research fields involving time-distorted, high entropy signals.
Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans
Authors: Li Cheng-Lin , Pu Mintie , Wang Wenke , Chaturbedi Amaresh , Emerson Felicity J. , Lee Siu Sylvia
Published: September 2021

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 inC.elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed “aging-specific repressive regions” (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in theC.elegansgenome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging inC.elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.
Multilevel factor analysis of flipped classroom in dental education: A 3-year randomized controlled trial
Authors: Wang Zuo , Kohno Eiko Yoshida , Fueki Kenji , Ueno Takeshi , Inamochi Yuka , Takada Kazuki , Wakabayashi Noriyuki
Published: September 2021

Purpose

Previous studies have rarely attempted to test the confounding factors that may affect learning outcomes of the flipped classroom. The purpose of this study was to assess how flipped classrooms affect the acquisition of knowledge in clinical dental education based on multilevel factor analysis.

Method

The authors conducted a 3-year (2017, 2018, and 2019) randomized controlled trial in a series of introductory prosthodontics courses in dental education. A total of 137 participants were randomly assigned to flipped classroom (n = 70, 51%) or lecture (n = 67, 49%) formats. The flipped group was instructed to self-learn knowledge-based content through online preparation materials, including videos and text, while the lecture group was given text only. Both groups were provided with the same study content and opportunities for different styles of learning. The session attendance rate and number of times the materials were accessed were monitored. Individual and team readiness assurance tests (IRAT/TRAT) were conducted to evaluate knowledge acquisition. A multilevel linear regression analysis was conducted on both instructional styles (flipped vs. lecture) as an intervention factor, and confounding factors that could affect the outcomes were implemented.

Results

The average number of online accesses was 2.5 times per session in the flipped group and 1.2 in the lecture group, with a significant difference (p < .05). The average IRAT score was significantly higher in the flipped than in the lecture group (effect size [ES] 0.58, p < .001). The number of online accesses was significantly and positively correlated with IRAT scores (0.6 [0.4, 0.8]). The instructional style was significantly and positively correlated with TRAT scores (coefficient [95% confidence interval]: 4.6 [2.0, 7.3]), but it was not correlated with IRAT (4.3 [-0.45, 9.0]).

Conclusions

The flipped classroom was more effective than the lecture format regarding knowledge acquisition; however, the decisive factor was not the instructional style but the number of individual learning occasions. The employment of the flipped classroom was the decisive factor for team-based learning outcomes.
Voltage-dependent plasticity of spin-polarized conductance in phenyl-based single-molecule magnetic tunnel junctions
Authors: Madadi Asl Mojtaba , Ramezani Akbarabadi Saeideh
Published: September 2021

Synaptic strengths between neurons in brain networks are highly adaptive due to synaptic plasticity. Spike-timing-dependent plasticity (STDP) is a form of synaptic plasticity induced by temporal correlations between the firing activity of neurons. The development of experimental techniques in recent years enabled the realization of brain-inspired neuromorphic devices. Particularly, magnetic tunnel junctions (MTJs) provide a suitable means for the implementation of learning processes in molecular junctions. Here, we first considered a two-neuron motif subjected to STDP. By employing theoretical analysis and computer simulations we showed that the dynamics and emergent structure of the motif can be predicted by introducing an effective two-neuron synaptic conductance. Then, we considered a phenyl-based single-molecule MTJ connected to two ferromagnetic (FM) cobalt electrodes and investigated its electrical properties using the non-equilibrium Green’s function (NEGF) formalism. Similar to the two-neuron motif, we introduced an effective spin-polarized conductance in the MTJ. Depending on the polarity, frequency and strength of the bias voltage applied to the MTJ, the system can learn input signals by adaptive changes of the effective conductance. Interestingly, this voltage-dependent plasticity is an intrinsic property of the MTJ where its behavior is reminiscent of the classical temporally asymmetric STDP. Furthermore, the shape of voltage-dependent plasticity in the MTJ is determined by the molecule-electrode coupling strength or the length of the molecule. Our results may be relevant for the development of single-molecule devices that capture the adaptive properties of synapses in the brain.
Duration of intervals in the care seeking pathway for lung cancer in Bangladesh: A journey from symptoms triggering consultation to receipt of treatment
Authors: Ansar Adnan , Lewis Virginia , McDonald Christine Faye , Liu Chaojie , Rahman Muhammad Aziz
Published: September 2021

Timeliness in seeking care is critical for lung cancer patients’ survival and better prognosis. The care seeking trajectory of patients with lung cancer in Bangladesh has not been explored, despite the differences in health systems and structures compared to high income countries. This study investigated the symptoms triggering healthcare seeking, preferred healthcare providers (including informal healthcare providers such as pharmacy retailers, village doctors, and “traditional healers”), and the duration of intervals in the lung cancer care pathway of patients in Bangladesh. A cross-sectional study was conducted in three tertiary care hospitals in Bangladesh among diagnosed lung cancer patients through face-to-face interview and medical record review. Time intervals from onset of symptom and care seeking events were calculated and compared between those who sought initial care from different providers using Wilcoxon rank sum tests. Among 418 study participants, the majority (90%) of whom were males, with a mean age of 57 ±9.86 years, cough and chest pain were the most common (23%) combination of symptoms triggering healthcare seeking. About two-thirds of the total respondents (60%) went to informal healthcare providers as their first point of contact. Living in rural areas, lower levels of education and lower income were associated with seeking care from such providers. The median duration between onset of symptom to confirmation of diagnosis was 121 days, between confirmation of diagnosis and initiation of treatment was 22 days, and between onset of symptom and initiation of treatment was 151 days. Pre-diagnosis durations were longer for those who had sought initial care from an informal provider (p<0.05). Time to first contact with a health provider was shorter in this study compared to other developed and developing countries but utilizing informal healthcare providers caused delays in diagnosis and initiation of treatment. Encouraging people to seek care from a formal healthcare provider may reduce the overall duration of the care seeking pathway.
Efficacy and radiographic analysis of oblique lumbar interbody fusion in treating adult spinal deformity
Authors: Jo Dae-Jean , Seo Eun-Min
Published: September 2021

Adult spinal deformity (ASD) is usually rigid and requires a combined anterior–posterior approach for deformity correction. Anterior lumbar interbody fusion (ALIF) allows direct access to the disc space and placement of a large interbody graft. A larger interbody graft facilitates correction of ASD. However, an anterior approach carries significant risks. Lateral lumbar interbody fusion (LLIF) through a minimally invasive approach has recently been used for ASD. The present study was performed to evaluate the effectiveness of oblique lumbar interbody fusion (OLIF) in the treatment of ASD. We performed a retrospective study utilizing the data of 74 patients with ASD. The inclusion criteria were lumbar coronal Cobb angle > 20°, pelvic incidence (PI)–lumbar lordosis (LL) mismatch > 10°, and minimum follow–up of 2 years. Patients were divided into two groups: ALIF combined with posterior spinal fixation (ALIF+PSF) (n = 38) and OLIF combined with posterior spinal fixation (OLIF+PSF) (n = 36). The perioperative spinal deformity radiographic parameters, complications, and health-related quality of life (HRQoL) outcomes were assessed and compared between the two groups. The preoperative sagittal vertical axis (SVA), LL, PI–LL mismatch, and lumbar Cobb angles were similar between the two groups. Patients in the OLIF+PSF group had a slightly higher mean number of interbody fusion levels than those in the ALIF+PSF group. At the final follow–up, all radiographic parameters and HRQoL scores were similar between the two groups. However, the rates of perioperative complications were higher in the ALIF+PSF than OLIF+PSF group. The ALIF+PSF and OLIF+PSF groups showed similar radiographic and HRQoL outcomes. These observations suggest that OLIF is a safe and reliable surgical treatment option for ASD.
Important roles of the human leukocyte antigen class I and II molecules and their associated genes in the autoimmune coagulation factor XIII deficiency via whole-exome sequencing analysis
Authors: Osaki Tsukasa , Souri Masayoshi , Ichinose Akitada
Published: September 2021

Autoimmune coagulation factor XIII deficiency is a bleeding disorder caused by the formation of autoantibodies against the coagulation factor XIII (FXIII); however, the molecular mechanism underlying this process is unknown. Therefore, in the present study, we aimed to elucidate this mechanism by performing whole-exome sequencing analysis of 20 cases of autoimmune FXIII deficiency. We identified approximately 21,788–23,916 variants in each case. In addition to their ability to activate T cells, present antigens, and immune tolerance, the candidate alleles were further narrowed down according to their allelic frequencies and the magnitude of damage caused by the substitution of amino acids. After selecting 44 candidate alleles, we investigated whether they were associated with the FXIII inhibitory titers and/or the anti-FXIII autoantibodies. We found that two polymorphisms whose variant allele frequencies were significantly lower in the patients tended to decrease FXIII inhibitory titers as the number of variant alleles increased. We also found that five polymorphisms whose variant allele frequencies were significantly higher in the patients tended to increase the levels of the anti-FXIII autoantibodies as the number of variant alleles increased. All of these polymorphisms were found in the human leukocyte antigen (HLA) class I and II molecules and their associated genes. In particular, the HLA class II molecule and its associated genes were found to be involved in the presentation of foreign antigens as well as the negative regulation of the proliferation of T-cells and the release of cytokines. Polymorphisms in the HLA class II molecules and the cytotoxic T lymphocyte antigen 4 have been reported to be associated with the development of autoantibodies in acquired hemophilia A. Therefore, we hypothesized that these polymorphisms may be associated with the development of autoantibodies in autoimmune FXIII deficiency.
Real-life use of tocilizumab with or without corticosteroid in hospitalized patients with moderate-to-severe COVID-19 pneumonia: A retrospective cohort study
Authors: Russo Gianluca , Solimini Angelo , Zuccalà Paola , Zingaropoli Maria Antonella , Carraro Anna , Pasculli Patrizia , Perri Valentina , Marocco Raffaella , Kertusha Blerta , Del Borgo Cosmo , Del Giudice Emanuela , Fondaco Laura , Tieghi Tiziana , D’Agostino Claudia , Oliva Alessandra , Vullo Vincenzo , Ciardi Maria Rosa , Mastroianni Claudio Maria , Lichtner Miriam
Published: September 2021

Objective

To evaluate the effectiveness of Tocilizumab (with or without corticosteroids) in a real-life context among moderate-to-severe COVID-19 patients hospitalized at the Infectious Diseases ward of two hospitals in Lazio region, Italy, during the first wave of SARS-CoV-2 pandemic.

Method

We conducted a retrospective cohort study among moderate-to-severe COVID-19 pneumonia to assess the influence of tocilizumab (with or without corticosteroids) on: 1) primary composite outcome: risk for death/invasive mechanical ventilation/ICU-transfer at 14 days from hospital admission; 2) secondary outcome: COVID-related death only. Both outcomes were also assessed at 28 days and restricted to baseline more severe cases. We also evaluated the safety of tocilizumab.

Results

Overall, 412 patients were recruited, being affected by mild (6.8%), moderate (66.3%) or severe (26.9%) COVID-19 at baseline. The median participant’ age was 63 years, 56.5% were men, the sum of comorbidities was 1.34 (±1.44), and the median time from symptom onset to hospital admission was 7 [3–10] days. Patients were subdivided in 4 treatment groups: standard of care (SoC) only (n = 172), SoC plus corticosteroid (n = 65), SoC plus tocilizumab (n = 50), SoC plus tocilizumab and corticosteroid (n = 125). Twenty-six (6.3%) patients underwent intubation, and 37 (9%) COVID-related deaths were recorded. After adjusting for several factors, multivariate analysis showed that tocilizumab (with or without corticosteroids) was associated to improved primary and secondary outcomes at 14 days, and at 28-days only when tocilizumab administered without corticosteroid. Among more severe cases the protective effect of tocilizumab (± corticosteroids) was observed at both time-points. No safety concerns were recorded.

Conclusion

Although contrasting results from randomized clinical trials to date, in our experience tocilizumab was a safe and efficacious therapeutic option for patients with moderate-to-severe COVID-19 pneumonia. Its efficacy was improved by the concomitant administration of corticosteroids in patients affected by severe-COVID-19 pneumonia at baseline.
Genetic association of anthropometric traits with type 2 diabetes in ethnically endogamous Sindhi families
Authors: Mamtani Manju , Jaisinghani Manisha T. , Jaiswal Sujeet G. , Pipal Kanchan V. , Patel Ashwini A. , Kulkarni Hemant
Published: September 2021

Background

Ethnically endogamous populations can shed light on the genetics of type 2 diabetes. Such studies are lacking in India. We conducted this study to determine the genetic and environmental contributions of anthropometric traits to type 2 diabetes risk in the Sindhi families in central India.

Methods

We conducted a family study in Indian Sindhi families with at least one case of type 2 diabetes. Variance components methods were used to quantify the genetic association of 18 anthropometric traits with eight type 2 diabetes related traits. Univariate and bivariate polygenic models were used to determine the heritability, genetic and environmental correlation of anthropometric traits with type 2 diabetes related traits.

Results

We included 1,152 individuals from 112 phenotyped families. The ascertainment-bias corrected prevalence of type 2 diabetes was 35%. Waist circumference, hip circumference and the biceps, triceps, subscapular and medial calf skinfold thicknesses were polygenically and significantly associated with type 2 diabetes. The range of heritability of the anthropometric traits and type 2 diabetes related traits was 0.27–0.73 and 0.00–0.39, respectively. Heritability of type 2 diabetes as a discrete trait was 0.35. Heritability curves demonstrated a substantial local influence of type 2 diabetes related traits. Bivariate trait analyses showed that biceps and abdominal skinfold thickness and all waist-containing indexes were strongly genetically correlated with type 2 diabetes.

Conclusions

In this first study of Sindhi families, we found evidence for genetic and environmental concordance of anthropometric traits with type 2 diabetes. Future studies need to probe into the genetics of type 2 diabetes in this population.
‘A polyphonic tale’: Arendt, Cavarero and storytelling in Sarah Polley’s Stories We Tell (2012)
Authors: Angeli Silvia
Published: September 2021

This article proposes a reading of Sarah Polley’s Stories We Tell (2012) through the work of Hannah Arendt and Adriana Cavarero. Far from being a simple homage to her late mother Diane, Polley’s film is a ‘polyphonic tale’, a complex and multi-layered
narrative which allows for an exploration of the many functions of (cinematic) storytelling. Highlighting the close link between relating narratives and personal identity, the film sheds light on both the innate desire for biography that characterizes us as human beings and the complex and
dynamic relationship between storytellers and listeners. The way we tell stories affects the narrator(s), their audience and the fabric of the story itself in a process that ensures both continuity and change. Referring to Arendt’s notion of political storytelling, I conclude by suggesting
that Stories We Tell, like the Greek polis, functions as an ‘organized remembrance’, a community whose purpose is to preserve fragile human deeds and words from oblivion.
El retorno de las mujeres cosmológicas y originarias: el protagonismo de las mujeres indígenas en los centros de poder políticos y sociales en Brasil y en el mundo
Authors: Multini Belchior Maria Clara , Regina Rossi Célia
Published: September 2021

El artículo se compone de un marco teórico unido al relato de una experiencia en el campo de la fotografía, y tiene como objetivo reflexionar y provocar sobre la mujer indígena brasileña y su representación contemporánea. Investigando sus pautas de lucha durante la 1ª Marcha de las Mujeres Indígenas Territorio: nuestro cuerpo, nuestro espíritu, celebrada en Brasilia - Distrito Federal el 13 de agosto de 2019. Cuestionamos la mirada colonizadora sobre sus cuerpos e identidades, su visión del mundo, su forma de vida. Buscamos reflexionar sobre pautas importantes en las esferas política, económica y social y de qué forma la práctica y organización de estas mujeres coinciden con la emergencia de nuevas construcciones en el ámbito del poder. ¿Quiénes son estas mujeres cosmológicas y originarias, que regresan a sus lugares sagrados y han resistido durante más de cinco siglos en Brasil? La experiencia forma parte de un campo de observación y recogida de fotos que constituye el Trabajo Fin de Máster que estudia la representación de mujeres indígenas brasileñas contemporáneas, buscando la comprensión y traducción de su fuerza y ​​tradición a través de la visibilidad material proporcionada por la fotografía y métodos consistentes de análisis fotográfico, que cubren toda la complejidad que puede existir en la traducción de una mujer indígena.