bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of cardiovascular risk in adults with type 1 diabetes: poor concordance between the 2019 ESC risk classification and 10-year cardiovascular risk prediction according to the Steno Type 1 Risk Engine
Authors: Tecce Nicola , Masulli Maria , Lupoli Roberta , Della Pepa Giuseppe , Bozzetto Lutgarda , Palmisano Luisa , Rivellese Angela Albarosa , Riccardi Gabriele , Capaldo Brunella 
Published: October 2020

AbstractBackgroundPatients with type 1 diabetes (T1D) have higher mortality risk compared to the general population; this is largely due to increased rates of cardiovascular disease (CVD). As accurate CVD risk stratification is essential for an appropriate preventive strategy, we aimed to evaluate the concordance between 2019 European Society of Cardiology (ESC) CVD risk classification and the 10-year CVD risk prediction according to the Steno Type 1 Risk Engine (ST1RE) in adults with T1D.MethodsA cohort of 575 adults with T1D (272F/303M, mean age 36 ± 12 years) were studied. Patients were stratified in different CVD risk categories according to ESC criteria and the 10-year CVD risk prediction was estimated with ST1RE within each category.ResultsMen had higher BMI, WC, SBP than women, while no difference was found in HbA1c levels between genders. According to the ESC classification, 92.5% of patients aged < 35 years and 100% of patients ≥ 35 years were at very high/high risk. Conversely, using ST1RE to predict the 10-year CVD risk within each ESC category, among patients at very high risk according to ESC, almost all (99%) had a moderate CVD risk according to ST1RE if age < 35 years; among patients aged ≥35 years, the majority (59.1%) was at moderate risk and only 12% had a predicted very high risk by ST1RE. The presence of target organ damage or three o more CV risk factors, or early onset T1D of long duration (> 20 years) alone identified few patients (< 30%) among those aged ≥35 years, who were at very high risk according to ESC, in whom this condition was confirmed by ST1RE; conversely, the coexistence of two or more of these criteria identified about half of the patients at high/very high risk also according to this predicting algorithm. When only patients aged ≥ 50 years were considered, there was greater concordance between ESC classification and ST1RE prediction, since as many as 78% of those at high/very high risk according to ESC were confirmed as such also by ST1RE.ConclusionsUsing ESC criteria, a large proportion (45%) of T1D patients without CVD are classified at very high CVD risk; however, among them, none of those < 35 years and only 12% of those ≥ 35 years could be confirmed at very high CVD risk by the ST1RE predicting algorithm. More studies are needed to characterize the clinical and metabolic features of T1D patients that identify those at very high CVD risk, in whom a very aggressive cardioprotective treatment would be justified.
Rapid and easy-to-use ES cell manipulation device with a small groove near culturing wells
Authors: Funano Shun-ichi , Tone Daisuke , Ukai Hideki , Ueda Hiroki R. , Tanaka Yo 
Published: October 2020

Abstract
Objective
Production of genetically modified mice including Knock-out (KO) or Knock-in (KI) mice is necessary for organism-level phenotype analysis. Embryonic stem cell (ESC)-based technologies can produce many genetically modified mice with less time without crossing. However, a complicated manual operation is required to increase the number of ESC colonies. Here, the objective of this study was to design and demonstrate a new device to easily find colonies and carry them to microwells.

Results
We developed a polydimethylsiloxane-based device for easy manipulation and isolation of ESC colonies. By introducing ESC colonies into the groove placed near culturing microwells, users can easily find, pick up and carry ESC colonies to microwells. By hydrophilic treatment using bovine serum albumin, 2-μL droplets including colonies reached the microwell bottom. Operation time using this device was shortened for both beginners (2.3-fold) and experts (1.5-fold) compared to the conventional colony picking operation. Isolated ESC colonies were confirmed to have maintained pluripotency. This device is expected to promote research by shortening the isolation procedure for ESC colonies or other large cells (e.g. eggs or embryos) and shortening training time for beginners as a simple sorter.
Abscopal effect in pulmonary carcinoid tumor following ablative stereotactic body radiation therapy: a case report
Authors: Kareff Samuel A. , Lischalk Jonathan W. , Krochmal Rebecca , Kim Chul 
Published: October 2020

AbstractBackgroundThe abscopal effect was described as early as the 1950s, when untreated tumors demonstrated a response after radiation therapy was delivered to an untreated, distant site. The mechanisms underlying this global response to otherwise localized therapy remain unknown, though there is increasing evidence that increased antigen expression following ablative radiotherapy may play a role.Case presentationWe report a case of a 69-year-old African American woman with a history of metastatic typical pulmonary carcinoid with multiple lung nodules who had a significant decrease in size of an untreated left upper lobe nodule after stereotactic body radiation therapy to an oligoprogressive left lower lobe lesion.ConclusionsTo our knowledge, this report describes the first case of an abscopal effect in a typical pulmonary carcinoid. Further research is needed regarding the mechanisms responsible for this finding and the role of combining radiation therapy and cancer immunotherapy in patients with pulmonary carcinoid tumors.
Rockfall hazard in the Imja Glacial Lake, eastern Nepal
Authors: Khatiwada Durga , Dahal Ranjan Kumar 
Published: October 2020

AbstractIn Nepal, rockfall related studies are rarely conducted and are limited to the landslide study along with few case studies on rockfall events. Rockfall problems in Nepal are more frequent in the Higher Himalayan region than Midland and Lesser Himalayan regions. In the glaciated valley and glacial lakes, rockfall and associated tsunami like huge wave are a recently initiated research. In this context, a glacial lake of the Himalaya, named as Imja Glacial Lake situated in eastern Nepal has been selected to understand the rockfall problems and their possible consequences. The lake was formed at the end part of the Imja glacier. The northern valley slope of Imja Glacier Lake, i.e. southern slope of the Island Peak has serious problem of rockfall into the lake. Rockfall simulation was performed during this research with field data. Three different Plots were defined for simulation of rockfall. Among them, Plot III seems to be the most hazardous since the detached boulders on the higher elevation can enter into the lake with the maximum velocity of 40 m/s with pre-impact energy more than 3500 kJ. This can develop a surge in the lake water that can break moraine dam. This leads to a serious threat to the downstream communities. Moreover, this research confirms that the rockfall hazard in the higher mountain region of Nepal is critical to creating flash floods due to tsunamis like surge in the lake water and breaching of the dam.
Baseline sensitivity and resistance risk assessment of Valsa mali to pyraclostrobin
Authors: Feng Hao , Wang Shuai , Liu Zhaoyang , Miao Jianqiang , Zhou Mingxia , Huang Lili 
Published: October 2020

AbstractPyraclostrobin, a quinone outside inhibitor (QoI) fungicide, has been registered to control apple tree Valsa canker (AVC) caused by Valsa mali in China. However, there is no data available regarding the resistance risk of V. mali to pyraclostrobin. In this study, the sensitivities of 120 V. mali isolates to pyraclostrobin were detected. The isolates were collected from apple orchards with no application of pyraclostrob at six provinces in China during 2013–2015, and showed similar sensitivity to pyraclostrobin. The EC50 values of these 120 V. mali isolates to pyraclostrobin ranged from 0.0014 to 0.0240 μg/mL, indicating an excellent inhibitory efficacy of pyraclostrobin to the pathogen. The EC50 values were distributed as a unimodal curve with a mean value of 0.0091 μg/mL, and the mean EC50 displayed correlation with geographic location. Meanwhile, three pyraclostrobin-resistant mutants (PR mutants) of V. mali were obtained using fungicide adaption method, with a resistance factor (RF) of 41.0, 56.8 and 22.0, respectively. The mutants showed a stable resistance to pyraclostrobin after 10 transfers on pyraclostrobin-free medium. Comparing with the corresponding parental isolates, the hyphal growth, mycelial dry weight and pathogenicity of PR mutants were significantly reduced, but the number of propagules showed no significant difference. More importantly, no cross-resistance of PR mutants to pyraclostrobin, tebuconazole, difenoconazole, imazalil and thiophanate-methyl was detected. In conclusion, V. mali showed a moderate risk to pyraclostrobin, and pyraclostrobin could be used as an alternative fungicide to control AVC in the field in China.
Analytic formulas for complete and incomplete first-order TEM moments below ground in a conductive half-space
Authors: Fullagar Peter K. , Schaa Ralf 
Published: October 2020

In the resistive limit, discrete conductors give rise to magnetic dipole fields. Magnetostatic modeling of time integrals, or moments, of transient electromagnetic (TEM) data therefore offers a means for fast approximate 3D modeling and inversion of TEM data sets. In our approximate inversion scheme, the net TEM moment response is represented as the combination of discrete conductor and uniform host responses. The inversion algorithm first estimates a homogeneous host conductivity, and then it subtracts the host response and fits the residual moment data by adjusting the conductivities of cells comprising a 3D rectangular mesh. To expedite calculation of the host response, we have derived analytic formulas for first-order TEM moments produced on and under the ground by a horizontal electric dipole on the surface of a homogeneous conductive half-space. We present analytic expressions for idealized all-time “complete” moments, or resistive limits, as well as for realizable finite-time “incomplete” moments. The moments produced by an arbitrary horizontal polygonal loop are determined by combining contributions from appropriately oriented electric dipoles. Downhole TEM moments computed with the new expressions reveal substantial differences between incomplete and complete moments when early time data are excluded and between step and impulse response incomplete moments. The role of the formulas in the first stage of our moment-based 3D inversion scheme is illustrated via analysis of downhole TEM data recorded at Santander, Peru. The host conductivity of best fit for early time B-field moments is 2.40 mS/m, consistent with apparent conductivities derived from ground TEM data recorded in the same area.
Meta-Analysis of PD-L1 Expression As a Predictor of Survival After Checkpoint Blockade
Authors: Arfè Andrea , Fell Geoffrey , Alexander Brian , Awad Mark M. , Rodig Scott J. , Trippa Lorenzo , Schoenfeld Jonathan D. 
Published: October 2020

PURPOSE Programmed cell death receptor ligand 1 (PD-L1) expression is the most studied biomarker to predict the efficacy of immune checkpoint inhibitors (ICIs), but its clinical significance is controversial. We estimated the distribution of PD-L1 expression scores (ie, tumor proportion score or combined proportion score) and the relationship between PD-L1 levels and ICIs’ impact on overall survival (OS). METHODS We reconstructed, pooled, and analyzed individual-level data on 7,617 patients with cancer from 14 randomized clinical trials. The effects of ICIs were quantified using differences in 24-month restricted mean survival times (ΔRMSTs; ie, the increase in life expectancy truncated at 2 years associated with ICI therapy). In a simulation study, we compared standard randomized clinical trial designs with a trial design that leverages meta-analytic results like ours. RESULTS Approximately 93% of patients had a PD-L1 expression ≤ 5% (66% of patients) or > 50% (27% of patients). OS improves with ICIs regardless of PD-L1 expression level, which predicts the benefits’ magnitude. For patients with non–small-cell lung cancer (NSCLC), ΔRMSTs ranged from 1.4 months (95% probability interval [PI], 0.7 to 2.2 months) for PD-L1 expression ≤ 1% to 4.1 months (95% PI, 3.2 to 5.2 months) for PD-L1 expression > 80%. For patients with non-NSCLC tumors, ΔRMSTs ranged from 0.8 months (95% PI, −0.1 to 1.7 months) to 2.3 months (95% PI, 1.3 to 4.4 months), again for PD-L1 expression levels of ≤ 1% and > 80%, respectively. Simulations suggested that designs tailored to meta-analytic results can detect the effects of ICIs in PD-L1 subgroups with higher probability (> 15%) than standard designs. CONCLUSION The practice of dichotomizing the range of PD-L1 expression scores is inadequate for patient stratification. Meta-analytic estimates of the distribution of PD-L1 scores and subgroup-specific treatment effects can improve the designs of future trials of ICIs.
FSHB  Transcription is Regulated by a Novel 5′ Distal Enhancer With a Fertility-Associated Single Nucleotide Polymorphism
Authors: Bohaczuk Stephanie C , Thackray Varykina G , Shen Jia , Skowronska-Krawczyk Dorota , Mellon Pamela L 
Published: October 2020

Abstract
The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, signal the gonads to regulate male and female fertility. FSH is critical for female fertility as it regulates oocyte maturation, ovulation, and hormone synthesis. Multiple genome-wide association studies (GWAS) link a 130 Kb locus at 11p14.1, which encompasses the FSH beta-subunit (FSHB) gene, with fertility-related traits that include polycystic ovary syndrome, age of natural menopause, and dizygotic twinning. The most statistically significant single nucleotide polymorphism from several GWAS studies (rs11031006) resides within a highly conserved 450 bp region 26 Kb upstream of the human FSHB gene. Given that sequence conservation suggests an important biological function, we hypothesized that the region could regulate FSHB transcription. In luciferase assays, the conserved region enhanced FSHB transcription and gel shifts identified a binding site for Steroidogenic factor 1 (SF1) contributing to its function. Analysis of mouse pituitary single-cell ATAC-seq demonstrated open chromatin at the conserved region exclusive to a gonadotrope cell-type cluster. Additionally, enhancer-associated histone markers were identified by immunoprecipitation of chromatin from mouse whole pituitary and an immortalized mouse gonadotrope-derived LβT2 cell line at the conserved region. Furthermore, we found that the rs11031006 minor allele upregulated FSHB transcription via increased SF1 binding to the enhancer. All together, these results identify a novel upstream regulator of FSHB transcription and indicate that rs11031006 can modulate FSH levels.
Anaesthetic management of patients undergoing deep brain simulation: A retrospective review of 8 cases from a tertiary care center of Pakistan
Authors: Ahmed Usama , Shafiq Faraz , Kumar Dileep , Ahsan Khalid , Ghaffar Waleed Bin , Bari Ehsan 
Published: October 2020

Objectives: To review anaesthesia related outcome, perioperative complications and overall length of stay (LOS) in hospital for patients who had deep brain stimulation (DBS).
Methods: The study was retrospective review of patients medical records diagnosed with Parkinson disease (PD) and underwent DBS at The Aga Khan University Hospital, Karachi from 2017-2019. Data was reviewed from file notes and patient chart and recorded on predesigned Performa. Frequency and percentages were used to present the data.
Results: All patients were anaesthetized using Sleep-Awake-Sleep technique (SAS). Dexmedetomidine was mainly used for conscious sedation. Bispectral index monitor (BIS) was used to monitor the depth of sedation, and kept between 70-85 during sedative phase. All patients had successful intraoperative neurological monitoring, stimulation, and placement of electrodes. Total duration of anesthesia varied significantly in between the patients. Maximum duration was 600 minutes. None of our patient had any intraoperative event related to anaesthetic management. Overall five patients had some adverse events during ward stay. Mean LOS in hospital was four days.
Conclusion: Anaesthetic management of DBS is well-tolerated. It requires dedicated team. The SAS technique is excellent for intraoperative neurophysiological monitoring. Careful selection of sedative agents and monitoring depth of anaesthesia using BIS would be beneficial in terms of improving related outcomes.
doi: https://doi.org/10.12669/pjms.36.7.2870
How to cite this:Ahmed U, Shafiq F, Kumar D, Ahsan K, Ghaffar W, Bari E. Anaesthetic management of patients undergoing deep brain simulation: A retrospective review of 8 cases from a tertiary care center of Pakistan. Pak J Med Sci. 2020;36(7):1737-1741. doi: https://doi.org/10.12669/pjms.36.7.2870
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.
Developing excellence in biostatistics leadership, training and science in Africa: How the Sub-Saharan Africa Consortium for Advanced Biostatistics (SSACAB) training unites expertise to deliver excellence
Authors: Chirwa Tobias F. , Matsena Zingoni Zvifadzo , Munyewende Pascalia , Manda Samuel O. , Mwambi Henry , Kandala Ngianga-Bakwin , Kinyanjui Samson , Young Taryn , Musenge Eustasius , Simbeye Jupiter , Musonda Patrick , Mahande Michael Johnson , Weke Patrick , Onyango Nelson Owuor , Kazembe Lawrence , Tumwesigye Nazarius Mboma , Zuma Khangelani , Yende-Zuma Nonhlanhla , Omanyondo  Ohambe Marie-Claire , Kweku Emmanuel Nakua , Maposa Innocent , Ayele Birhanu , Achia Thomas , Machekano Rhoderick , Thabane Lehana , Levin Jonathan , Eijkemans Marinus J.C. , Carpenter James , Chasela Charles , Klipstein-Grobusch Kerstin , Todd Jim 
Published: October 2020

The increase in health research in sub-Saharan Africa (SSA) has generated large amounts of data and led to a high demand for biostatisticians to analyse these data locally and quickly. Donor-funded initiatives exist to address the dearth in statistical capacity, but few initiatives have been led by African institutions. The Sub-Saharan African Consortium for Advanced Biostatistics (SSACAB) aims to improve biostatistical capacity in Africa according to the needs identified by African institutions, through (collaborative) masters and doctoral training in biostatistics. We describe the SSACAB Consortium, which comprises 11 universities and four research institutions- supported by four European universities. SSACAB builds on existing resources to strengthen biostatistics for health research with a focus on supporting biostatisticians to become research leaders; building a critical mass of biostatisticians, and networking institutions and biostatisticians across SSA. In 2015 only four institutions had established Masters programmes in biostatistics and SSACAB supported the remaining institutions to develop Masters programmes. In 2019 the University of the Witwatersrand became the first African institution to gain Royal Statistical Society accreditation for a Biostatistics MSc programme. A total of 150 fellows have been awarded scholarships to date of which 123 are Masters fellowships (41 female) of which with 58 have already graduated. Graduates have been employed in African academic (19) and research (15) institutions and 10 have enrolled for PhD studies. A total of 27 (10 female) PhD fellowships have been awarded; 4 of them are due to graduate by 2020. To date, SSACAB Masters and PhD students have published 17 and 31 peer-reviewed articles, respectively. SSACAB has also facilitated well-attended conferences, face-to-face and online short courses. Pooling the limited biostatistics resources in SSA, and combining with co-funding from external partners is an effective strategy for the development and teaching of advanced biostatistics methods, supervision and mentoring of PhD candidates.
Development of the Video Analysis Scale of Engagement (VASE) for people with advanced dementia
Authors: Daniel Lai L.L. , Crutch Sebastian J. , West Julian , Harding Emma , Brotherhood Emilie V. , Takhar Rohan , Firth Nicholas , Camic Paul M. 
Published: October 2020

Background: The current study sought to develop a valid, reliable and unobtrusive tablet computer-based observational measure to assess engagement of people with advanced dementia. The Video Analysis Scale of Engagement (VASE) was designed to enable the rating of moment-by-moment changes in engagement during an activity, which would be useful for both future research and current residential care.Methods: An initial version of the VASE was tested. Face validity and content validity were assessed to validate an operational definition of engagement and develop an acceptable protocol for the scale. Thirty-seven non-professional and professional volunteers were recruited to view and rate level of engagement in music activities using the VASE.Results: An inter-class coefficient (ICC) test gave a high level of rating agreement across professionals and non-professionals. However, the ICC results of within-professionals were mixed. Linear mixed modelling suggested that the types of interventions (active or passive music listening), the particular intervention session being rated, time period of video and the age of raters could affect the ratings.Conclusions: Results suggested that raters used the VASE in a dynamic fashion and that the measure was able to distinguish between interventions. Further investigation and adjustments are warranted for this to be considered a valid and reliable scale in the measurement of engagement of people with advanced dementia in a residential care setting.
Modeling of pedagogical support for self-development of adolescents in additional education in the context of the methodology of the reflexive-value approach
Authors: Ivanova Irina 
Published: October 2020

The change in the social and educational situation in the country has actualized the development of subject-oriented models of pedagogical support for students, the search for effective ways to create conditions for the self-development of students. In modern school programs, as well as in educational programs of additional education for children, there are practically no special classes devoted to the construction and implementation of self-development projects by adolescents. The article proposes a model of pedagogical support for self-development of adolescents in additional education, methodologically based on the reflexive-value approach developed by the author within the framework of the scientific school of M.I. Rozhkov, and technologically based on the compilation and implementation of individual self-development projects by adolescents. The presented model can be considered as a pedagogical product and educational resource that allows solving a whole range of problems based on the personal and social needs of both adolescents themselves and society as a whole. The implementation of the presented model presupposes building the educational process in the additional education of children with a focus on the self-development of students, while accompaniment is considered as a special type of pedagogical interaction aimed at stimulating pupils' awareness of the meaning of their own life and its value components and building on their basis a project of their own life.
Acknowledgments: The reported study was funded by RFBR, project number 20-013-00616.