bluuebunny/crossref_metadata_2025 huggingface dataset:
2-5THE DETERMINANT OF CENTRAL BLOOD PRESSURE IN TYPE 2 DIABETES PATIENTS
Authors: Khumaedi Anandhara Indriani , Nugroho Pringgodigdo , Purnamasari Dyah
Published: July 2020

Introduction:

Blood pressure (BP) control has been long known to have a role in reducing mortality and morbidity in type 2 diabetes (T2DM) patients. However, routine office BP measurement using brachial BP failed to represent true aortic BP reflected in target organs such as heart, kidney, and brain due to pulse pressure amplification and pulse wave reflection throughout the arterial tree. Several studies suggested that central BP might be a better predictor for cardiovascular (CV) risk than brachial BP in various populations. This study aimed to see the relationship between central systolic blood pressure (cSBP) with various demographic and diabetes-related parameters.

Methods:

This is a cross-sectional study involving 95 T2DM patients. Office blood pressure was measured using Omron® automatic sphygmomanometer. Meanwhile, central blood pressure was measured using SphygmoCor® XCEL. Diabetes-related parameters measured in this study are duration, A1C, and albumin-to-creatinine ratio (ACR). The analysis was conducted in all subjects, and in subgroup based on hypertensive status.

Result:

Among 95 T2DM patients were recruited; 70,5% of them are female. The mean age in this study was 48 years old (CI: 47,3 – 50,5); and mean BMI was 26 kg/m2 (CI: 25,6 – 27,3). Fifty-point-five percent of patients in this study were hypertensive. Central SBP were obviously, higher in patients with hypertension compared to non-hypertension (122,7 mmHg [CI: 93 – 191] vs 136,1 mmHg [CI: 131,4 – 140,8] respectively) and BP amplification (bSBP – cSBP) was more profound in hypertensive group (18,1 mmHg [CI:16,9 – 19,2]) compared to non-hypertensive group (14,5 mmHg [CI: 13,0 – 15,2]) respectively. Overall, a strong correlation found between bSBP and cSBP (R2 = 0,975). Multivariate analysis showed bSBP remained the only factor positively associated with cSBP. In subgroup analysis, bSBP showed strong correlation to cSBP both in hypertensive group and in non-hypertensive group (R2 = 0,987 and R2 = 0,977, respectively). In multivariate analysis, bSBP remained the only predictor of cSBP in hypertensive group, whereas in non-hypertensive group bSBP and female were predictors of cSBP. None of the diabetes-related parameters (duration, HbA1C, and ACR) are correlated with cSBP.

Result:

Agreement between cSBP and bSBP is very strong both in all subjects and in subgroup analysis. This might suggest that although cSBP proven superior than bSBP regarding CV risk predictor and target organ damage, high concordance correlation might suggest that these are still interchangeable, especially when central BP measurement is not convenient.
3-1INTRACRANIAL ARTERY STENOSIS PATTERN IN ISCHEMIC STROKE PATIENTS THROUGH TRANSCRANIAL DOPPLER(TCD) IN DR. M. DJAMIL HOSPITAL, PADANG
Authors: Sutia Dedi , Indra Syarif , Busra Meldayeni , K Yoga setia
Published: July 2020

Background:

Intracranial artery stenosis is one of significant risk factors in the occurrence of vascular disorders. Intracranial artery stenosis occurs in 33% −50% in stroke patients and 50% in transient ischemic attack patients. Transcranial doppler sonography (TCD) is one of the modalities that can detect intracranial stenosis with 79% sensitivity and 94% specificity. Transcranial doppler sonography can detect stenosis or occlusion of middle cerebral artery (MCA), bifurcatio of Internal Carotid Artery (ICA), anterior cerebral artery (ACA), vertebral arteries (VA), basilar artery (BA), and Posterior Cerebral artery (PCA). According to RSUP DR. M. Djamil medical record data that was obtained in 2018, 35.2% patients experienced intracranial arterial blood vessel disorders based on the results of TCD examination. This study aims to determine the characteristics of intracranial artery stenosis patterns in ischemic stroke patients through TCD examination in RSUP. Dr. M. Djamil Padang.

Method:

This study was an adescriptive study. The population was ischemic stroke patients in the Neurology Outpatient Clinic of DR. M. Djamil Hospital, Padang, who underwent TCD examination from January 1st to December 30th, 2019, with an evaluation of mean flow velocity (MFV).

Results:

In this study, there were 192 subjects; 57.29% of subjects were male. The most dominant age range was 51–60 years (30.21%). There were 55.73% of subjects with normal TCD results, 35.42% with intracranial artery stenosis, and 8.85% with general atherosclerosis. Based on the location, intracranial arteries stenosis was found most often in the Left Middle Cerebral Artery (26.47%), followed by Right Middle Cerebral Artery and Right Vertebral Artery (8.82%).

Conclusion:

Middle Cerebral Artery (MCA) is the most common location of intracranial arteries stenosis that was found in ischemic stroke patients and predominantly occurred in the left cerebral hemisphere.
3-4FUROSEMIDE USE AS POSTPARTUM MANAGEMENT IN WOMEN WITH HYPERTENSIVE DISORDER OF PREGNANCY: A SYSTEMATIC REVIEW
Authors: Ampri Irfan A. H. , Adham Rara M. , Leonardo  , Ivan Ignatius
Published: July 2020

Introduction:

Hypertensive disorders of pregnancy affect 10 % of pregnancy worldwide. It is also complicated maternal mortality and morbidity. Hypertensive disorders may persist after delivery in the puerperal period up to 12 weeks postpartum. The physiologic changes in pregnancy revert to normal in the postpartum period. Including the return of fluid from interstitial and extravascular compartments into intravascular. The use of diuretics is more fitting in the postpartum period and as an additional anti-hypertensive agent.

Methods:

We formulated a specific search strategy and used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). PubMed, Cochrane, Scopus, Science Direct, and Ebscohost are used as the literature Database. The criteria of the included studies are as follows: human study, randomized controlled trial; relevant patient characteristic; outcome assessment. Two independent authors assessed the quality of the study. This systematic review used the Cochrane Risk of Bias Tool 2.0.

Results:

Database searching provides a total of 58 studies. A total of 29 studies are duplicates. Six studies are included in the qualitative synthesis. One study does not show the results of the trial. A total of five studies are used. All studies are randomized controlled trials. One study reveals that there was a significant difference in systolic blood pressure, diastolic blood pressure, and mean arterial pressure between the treatment group and the control group. Another study reveals that the use of furosemide reduces the use of another antihypertensive therapy on the hospital and when discharged. Three studies show the insignificant result in reducing anti-hypertensive agents and blood pressure.

Conclusion:

Furosemide use as an anti-hypertensive agent on the postpartum setting is still unclear. Furosemide therapy may be useful in reducing the risk of complications in a patient with severe preeclampsia on postpartum settings such as eclampsia and pulmonary edema. Furosemide may reduce the amounts of anti-hypertensive agents used. Length of stay is the hospital may not be affected by the use of furosemide. The additional high-quality study should be conducted to elucidate furosemide use as a puerperal anti-hypertensive agent.
3-6EFFECTIVENESS OF DEMONSTRATION COUNSELING METHOD ON KNOWLEDGE LEVEL REGARDING COMPLIANCE WITH DIET ON HYPERTENSION PATIENTS IN PUSKESMAS SUNGAI KAKAP, KUBU RAYA REGENCY, WEST KALIMANTAN
Authors: Islami Aditya , Nasution Bakrie Bayquni , Mustika Angnes Dera , Sonia Gatria , Purba Nur Harini
Published: July 2020

Background:

Hypertension is still a high cause of death and illness. The results of the 2018 Riskesdas study showed that there was an increase in the number of hypertension that remained permanently from 2013 to 2018. Hypertension was still ranked first in the highest number of non-communicable diseases in Sungai Kakap. The most common conventional education patterns used in Primary Health Care Facilities in the form of lecture methods are still seen to be ineffective in influencing the level of public knowledge of salt needs and other nutritional content as well as eating patterns suitable for hypertensive patients.

Methods:

This research is a quasi-experimental research design of One Group Pretest Posttest, the results of which will be analyzed descriptively and analytically. Samples were taken by purposive sampling totaling 32 people divided into two groups: the test group was given conventional counseling material lecture method and the test group was given counseling material with a demonstration method. Primary data were obtained from pretest and posttest using a questionnaire in hypertensive patients in the working area of Puskesmas Sungai Kakap. Data were analyzed using the unpaired T-test.

Result:

The mean post-test in the conventional lecture method group was 69.37 ± 16.11, and there were no significant differences in the comparison between pre-test and post-test scores. The mean post-test results in the group with the demonstration method treatment were worth 85.00 ± 14.60, and there was a significant difference in the comparison between the pre-test and post-test scores in the group with the counseling treatment demonstration method where the post-test value was higher than the post-test. The mean post-test score of the group using the demonstration method was of higher significance statistically when compared to the group with the lecture method (Sig <0.05, 95% confidence level) with a value difference of 15.62.

Hypertension Diet Counseling with Demonstration Method is more effective compared to Conventional Counseling Lecture Method.
3-8IMPACT OF CHRONIC HYPERTENSION ON IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Padmaridho Fachri , Muzakkar Akhtar Fajar
Published: July 2020

Background:

Chronic hypertension is one of the cardiovascular risk factors in the development of atherosclerosis, the process responsible for causing Acute Coronary Syndrome (ACS). Chronic hypertension needs attention not only as a risk factor for the incidence of ACS but also as a factor that can worsen output of ACS, so that deserves to get a tailored approach in management and follow up.

Objective:

To determine the relation between Chronic Hypertension with In-hospital mortality in patients with Acute Coronary Syndrome (ACS)

Method:

This study is a cross-sectional study conducted at Makassar Cardiac Center at Wahidin Sudirohusodo Hospital. The subjects of this study were patients with Acute Coronary Syndrome (ACS) from June 2018 to May 2019 with a total sampling method of 707 patients obtained from ACS Registry Indonesia. Data were analyzed using the Chi-Square method.

Results:

Patients with chronic hypertension had a significantly higher mortality rate (74.1%) compared to patients without chronic hypertension (p = 0.028). ACS patients with chronic hypertension had an increased risk of In-hospital mortality compared to those without, the odds ratio of 2.00 (p = 0.03)

Conclusion:

ACS patients with chronic hypertension are twice as likely to die at the hospital, so thus requiring a tailored approach in management and follow up for better outcomes.
4-2TAXANES-INDUCED CARDIOTOXICITY: A CASE REPORT IN BREAST CANCER PATIENT WITH PRE-EXISTING HYPERTENSION
Authors: Hartopo A.B. , Anggraeni V.Y. , Mumpuni H. , Jhundy B.W. , Hutajulu S.H.
Published: July 2020

Background:

Hypertension is one of the most common comorbidities reported in patients with malignancy. This population had a higher risk of developing cardiotoxicity. Taxanes is an important therapeutic agent for several malignancies, including breast cancers. Their applicability, however, is limited by cardiotoxicity. The optimal strategy to prevent and manage chemotherapy-related cardiotoxicity (CTRCT) has not yet implemented in clinical practices.

Case:

A 63 years old breast cancer female patient was planned to be treated with Taxanes for six cycles. On admission, there were no cardiovascular symptoms. The patient had a history of hypertension and no history of myocardial infarction or congestive heart failure (CHF). Baseline transthoracic echocardiogram demonstrated normal left ventricular ejection fraction (LVEF) 66%. She received calcium channel blocker for her hypertension during chemotherapy. After the second cycle, the patient experienced palpitation, and there were no other cardiovascular symptoms. Electrocardiogram showed Left Bundle Branch Block. Echocardiogram revealed LVEF 46% with anteroseptal and inferoseptal hypokinetic. She was suspected as CHF chemotherapy-induced. Taxane was stopped, and she was treated with angiotensin receptor blocker, beta-blocker, and loop diuretic. Two months after therapy, her LVEF revealed partial recovery with LVEF 60% and no reported symptoms.

Conclusion:

Prophylactic agents targeting pre-existing cardiac risk factor has not been implemented in clinical practice but may soon change. Early detection and prompt management appear crucial to reverse left ventricular dysfunction in cancer patients receiving taxanes, especially in patients with pre-existing hypertension.
4-3RENAL DENERVATION FOR RESISTANT HYPERTENSION POST-SIMPLICITY-3 HTN TRIAL: META-ANALYSIS AND SYSTEMATIC REVIEW
Authors: Santoso Jimmy O. , Panjaitan Harrison P.B.
Published: July 2020

Background:

Following the result from SIMPLICITY-3 trial that failed to show the benefit of renal denervation over sham control, the interest on renal denervation had fallen into hibernation. However, there were some authors indicated that SIMPLICITY-3 trial result seemed to have major problems regarding incomplete denervation that led experts to researched and carefully designed studies regarding renal denervation. Since then, there was three carefully-designed, sham-controlled studies published about the issue. However, there was no published meta-analysis on randomized trials after SIMPLICITY-3 era. We aimed to conduct a meta-analysis of RCTs to determine the effect of renal denervation in resistant hypertension.

Methods:

A search on MEDLINE and EMBASE was conducted in January 2020. Randomized clinical studies comparing renal denervation and sham-controlled trial published after SIMPLICITY-3 trial were included for this meta-analysis.

Study selection:

only fully published RCT and abstracts of RCT comparing renal denervation and sham control for resistant hypertension published after SIMPLICITY-3 trial was included. Studies which were duplicated and non-randomized were excluded.

Results:

The analysis included 149 patients from 3 trials with a duration of follow up of 2–6 months. The reduction in 24-h ambulatory SBP was significantly greater in the renal denervation group compared to the sham procedure (WMD −4.74 mmHg, 95% CI −6.5, −2.99; p < 0,001). There was also significant reduction in 24-h DBP (WMD −3.11 mmHg, 95% CI −3.98, −2.23; p < 0,001), office SBP (WMD −7.1 mmHg, 95% CI −9.12, −5.08; p < 0,001), and office DBP (WMD −4,63 mmHg, 95% CI −5.98, −3.28; p < 0,001).

Conclusion:

Following SIMPLICITY-3 trial, there were positive results regarding renal denervation on resistant hypertension. Renal denervation significantly reduced blood pressure compared to sham control. Our meta-analysis underscores the importance of conducting new well-designed studies to confirm our observed results.
4-5THE RISK OF HYPERTENSION IN ADULTS EXPOSED TO SECONDHAND SMOKE: A META-ANALYSIS
Authors: William Andy , Ningrum Indra Utami Mutiara , Panjaitan Harrison Bernard
Published: July 2020

Background:

Overwhelming evidence supports the conclusion that cigarette smoking is associated with various adverse cardiovascular events, including hypertension. In addition, exposure to secondhand smoke (SHS) can be just as dangerous because of the lack of filters. However, the effect of secondhand smoke exposure in increasing the risk of hypertension is still unclear.

Objective:

To investigate the risk of hypertension from secondhand smoke exposure among adults who never smoked.

Method:

Systematic search was conducted using MEDLINE and Science Direct for studies up to January 2020, which reported the risk of hypertension in adults exposed to secondhand smoke compared to those who did not. The risk of bias was assessed using the Newcastle-Ottawa Scale.

Results:

A total of 8 studies were included in the main analysis. The total number of subjects across all studies was 5,059,347 subjects. The pooled unadjusted results showed that exposure to SHS was not associated with the risk of hypertension (pooled OR = 1.21; 95% CI: 0.91 – 0.61). However, the pooled adjusted OR did show an increased risk of hypertension among subjects exposed to SHS (pooled aOR = 1.25; 95% CI 1.12–1.40). Subgroup analysis showed a more definite risk in the female population (pooled aOR = 1.28; 95% CI 1.13–1.45).

Conclusion:

When adjustment for potential confounders was made, exposure to SHS was associated with a higher risk of developing hypertension. Therefore, exposure to SHS has a significant public health implication for the prevention of hypertension.
Posteromedial Approach to Tibial Plateau Fracture Nonunion
Authors: Shields Charlotte N. , Eftekhary Nima , Egol Kenneth A.
Published: July 2020

Tibial plateau fractures can involve planes that require reduction and stabilization from a posterior approach. This includes posteromedial, posterolateral, and posterior column shear type injuries. This video outlines the prone posteromedial approach to the tibial plateau for posterior column fracture exposure, reduction, and fixation.
Operative Fixation of a Displaced Midshaft Clavicle Fracture
Authors: Campbell David H. , McKee Michael D.
Published: July 2020

Midshaft clavicle fractures are frequently encountered orthopaedic injuries. Significant displacement portends a higher likelihood of nonunion and symptomatic malunion after nonoperative treatment. Surgical fixation has been shown to reduce the rate of these adverse outcomes. However, the benefit of surgery is narrowly defined and the decision to offer operative treatment involves a careful analysis of patient clinical factors, expectations, and concomitant injuries. In North America, fixation is most commonly performed with a precontoured plate and screw construct. Frequently, fracture patterns are amenable to direct reduction and primary bone healing, but the plate may also be used as a bridging construct for comminuted fractures. This video demonstrates the superior approach to clavicular plating. We detail the exposure, reduction, and fixation using lag screws and stabilization with a plate and screw construct.
Tibial Intramedullary Nail From a Suprapatellar Approach in a Semi-Extended Position
Authors: Darnley James E. , Petersen Kyle A. , Siesel Craig , Gelman Scott , Miller Eric T.
Published: July 2020

An intramedullary nail is a common and reliable treatment option for diaphyseal tibial fractures. One such approach for this technique is suprapatellar. This video shows the surgical technique of a tibial nail through a suprapatellar approach in a semi-extended position in a 22-year-old man with a distal third tibial shaft fracture.
Grossing Breast Cancer Specimens: A Comprehensive Review
Authors: Agarwal Apeksha N. , Ritter Jacob , Dornbluth Nella C. , Mais Daniel D. , Nazarullah Alia N.
Published: July 2020

Grossing breast specimens presents a unique challenge in the anatomic pathology laboratory, because the approach varies with the type of specimen received, the preoperative diagnosis, and the administration of neoadjuvant therapy. Furthermore, careful attention to preanalytic variables, such as time of fixation, is required. The specimen often lacks orienting anatomic landmarks, and accurately documenting margins in 3 dimensions requires a deliberate approach that is easily understood for future reference. This article will provide a comprehensive source for grossing commonly received breast specimens, ranging from surgical biopsies to modified radical mastectomies and will describe the proper care of preanalytical measures to avoid compromise of biomarkers, methods to ensure adequate sampling of tissue for diagnosis, and assessment of tumor burden following neoadjuvant treatment.
Favorable Outcomes of Liver Transplantation from Controlled Circulatory Death Donors Using Normothermic Regional Perfusion Compared to Brain Death Donors
Authors: Savier Eric , Lim Chetana , Rayar Michel , Orlando Francesco , Boudjema Karim , Mohkam Kayvan , Lesurtel Mickael , Mabrut Jean Yves , Pittau Gabriella , Begdadi Nassiba , Cherqui Daniel , Adam René , Dondero Federica , Sepulveda Ailton , Soubrane Olivier , Bucur Petru , Barbier Louise , Salame Ephrem , Jasseron Carine , Antoine Corinne , Riou Bruno , Scatton Olivier
Published: July 2020

Background.

Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT.

Methods.

This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT.

Results.

A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1–4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68).

Conclusions.

This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.
Pulse-Controlled Amplification – a new powerful tool for front-line diagnostics
Authors: Müller Katharina , Daßen Sarah , Holowachuk Scott , Zwirglmaier Katrin , Stehr Joachim , Buersgens Federico , Ullerich Lars , Stoecker Kilian
Published: July 2020

Molecular diagnostics has become essential in the identification of many infectious diseases, and the detection of nucleic acids often serves as the gold standard technique for most infectious agents. However, established techniques like polymerase chain reaction (PCR) are time-consuming laboratory-bound techniques. Here we present an alternative method for the rapid identification of infectious agents using pulse-controlled amplification (PCA). PCA is a next generation nucleic acid amplification technology that uses rapid energy pulses to heat microcyclers (micro-scale metal heating elements embedded directly in the amplification reaction) for a few microseconds, thus only heating a small fraction of the reaction volume. The heated microcyclers cool off nearly instantaneously, resulting in ultra-fast heating and cooling cycles during which classic amplification of a target sequence takes place. This reduces the overall amplification time by a factor of up to 10, enabling a sample-to-result workflow in just 15 minutes, while running on a small and portable prototype device. We could demonstrate the efficacy of this technology in two assays, one for a nosocomial context targeting MecA conferred antibiotic resistance, and one for a biothreat scenario targeting Yersinia pestis. The observed limits of detection were 10 copies per reaction (purified DNA) for MecA in a methicillin resistant Staphylococcus aureus and 434 copies per reaction (purified DNA) or 9.8 cells per reaction (crude sample) of Yersinia pestis. Thus, PCA offers a decentralization of molecular diagnostics and is applicable whenever rapid, on-site detection of infectious agents is needed.
Foundational research and NIH funding enabling Emergency Use Authorization of remdesivir for COVID-19
Authors: Cleary Ekaterina Galkina , Jackson Matthew J. , Folchman-Wagner Zoë , Ledley Fred D.
Published: July 2020

Emergency Use Authorization for remdesivir months after discovery of COVID-19 is unprecedented. Typically, decades of research and public-sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to remdesivir’s biological target, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research 2000–2019. There were 6,567 RdRp-related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project Years with Costs of $1,875 million. NIH support for NcAn research comprised 4,607 Project Years with Costs of $4,612 million. Research Project grants accounted for 63% and 48% of Project Years for RdRp and NcAn respectively, but only 19% and 12% of Project Costs. Analytical modeling of research maturation estimates that RdRp and NcAn research passed an established maturity threshold in 2008 and 1994 respectively. Of 97 investigational compounds targeting RdRp since 1989, the three authorized for use entered clinical trials after both thresholds. This work demonstrates the scale of foundational research on the biological target and parent chemical structure of remdesivir that supported its discovery and development for COVID-19. This work identifies $6.5 billion in NIH funding for research leading to remdesivir, underscoring the role of public sector investments in basic research and research infrastructure that underlie new drugs and the response to emergent disease.

SIGNIFICANCE STATEMENT

Emergency Use Authorization of remdesivir for treating COVID-19 four months after discovery of this virus was enabled by decades of research on the drug’s biological target as well as other medicines with related chemical structures. The NIH contributed 6,800 years of grant funding to this research, totaling $6.5 billion (2000–2019), including funding for both investigator-initiated research and research infrastructure. Of this, $46.5 million was for research directly related to remdesivir. This analysis demonstrates the importance of a robust body of foundational research in responding rapidly to emergent diseases, and the substantial NIH contribution to this research. It also underscores the scale and significance of the public-sector investments that enable new drug discovery and development.
Daily viral kinetics and innate and adaptive immune responses assessment in COVID-19: a case series
Authors: Vetter Pauline , Eberhardt Christiane , Meyer Benjamin , Martinez Murillo Paola Andrea , Torriani Giulia , Pigny Fiona , Lemeille Sylvain , Cordey Samuel , Laubscher Florian , Vu Diem-Lan , Calame Adrien , Schibler Manuel , Jacquerioz Frederique , Rohner Géraldine Blanchard , Siegrist Claire-Anne , Kaiser Laurent , Didierlaurent Arnaud M , Eckerle Isabella
Published: July 2020

Background

Viral shedding patterns and its correlation with the immune responses of mildly symptomatic COVID-19 patients are still poorly characterized.

Methods

We enrolled the first five COVID-19 patients quarantined in our institution; none received immunomodulatory treatment. We monitored shedding of viral RNA and infectious virus by RT-PCR and cell culture from the upper respiratory tract, and characterized the kinetics of systemic innate and adaptive immune responses.

Results

Despite mild clinical disease, high viral loads and shedding of infectious virus were observed from the respiratory tract, with isolation of infectious virus and prolonged positivity by PCR up to day 7 and 19 post onset of symptoms, respectively. Robust innate responses characterized by an increase in activated CD14+CD16+ monocytes and cytokine responses were observed as early as 2 days after symptoms onset. Cellular and humoral SARS-CoV-2 specific adaptive responses were detectable in all patients.

Conclusion

Infectious virus shedding was limited to the first week of symptom onset in mild cases. A strong innate response, characterized by the mobilization of activated monocytes during the first days of infection, as well as SARS-CoV-2 specific antibodies were detectable, even in patients with mild disease.

We describe viral and immune profiles of the first five SARS-CoV-2 patients in our institution, showing high viral loads and infectious viral shedding in early acute disease. Mild patients mount an innate response sufficient for viral control and specific immunity.
Atmosome: The Personal Atmospheric Exposome
Authors: Bhimaraju Hari , Pandey Vaibhav , Nag Nitish , Jain Ramesh
Published: July 2020

Modern health research is increasingly separated into various “omics” fields. Omics provides a quantified approach to the total collective information about the various realms of biology. One aspect of omics called the exposome relates to the collective exposures an individual is placed in throughout their life. A subset of this exposome, is the atmospheric exposome, which we name as the “atmosome”. Air surrounds individuals from the moment they are born till they take their last breath. The atmosphere is constantly changing, given our location and surroundings are always dynamic throughout life. The atmosphere inevitably plays a massive role in our health such as impact on DNA damage, metabolism, skin integrity, and lung health. In this work, we discuss the significance of the atmosome in personalized health and present our atmosome sensing system. We developed and analyzed data from our IoT, microcontroller-based system which collects real-time individual air quality data and posts it to a cloud server for immediate access. Our experimental results demonstrate the accuracy of the data we collected and the avenues our system creates for direct lifestyle to environment correlations. Quantifying the individual atmosome is a next step in advancing personalized health and medical research. Our two main goals in this paper are to present the atmosome as a concept and to explain how to track it using low-cost electronics.
Three Dimensional Multi-gene Expression Maps Reveal Cell Fate Changes Associated with Laterality Reversal of Zebrafish Habenula
Authors: Wang Guo-Tzau , Pan He-Yen , Lang Wei-Han , Yu Yuan-Ding , Hsieh Chang-Huain , Kuan Yung-Shu
Published: July 2020

The conserved bilateral habenular nuclei (HA) in vertebrate diencephalon develop into compartmentalized structures containing neurons derived from different cell lineages. Despite extensive studies demonstrated that zebrafish larval HA display distinct left-right (L-R) asymmetry in gene expression and connectivity, the spatial gene expression domains were mainly obtained from two-dimensional (2D) snapshots of colorimetric RNAin situhybridization staining which could not properly reflect different HA neuronal lineages constructed in three-dimension (3D). Combing the tyramide-based fluorescent mRNAin situhybridization, confocal microscopy and customized imaging processing procedures, we have created spatial distribution maps of four genes for 4 day old zebrafish and in sibling fish whose L-R asymmetry was spontaneously reversed. 3D volumetric analyses showed that ratios ofcpd2, lov, ronandnrp1aexpression in L-R reversed HA were reversed according to the parapineal positions. However, the quantitative changes of gene expression in reversed larval brains do not mirror the gene expression level in the obverse larval brains. There were a total 87.78% increase oflov+nrp1a+and a total 12.45% decrease oflov+ron+double-positive neurons when the L-R asymmetry of HA was reversed. Thus, our volumetric analyses of the 3D maps indicate that changes of HA neuronal cell fates are associated with the reversal of HA laterality. These changes likely account for the behavior changes associated with HA laterality alterations.
A model of traumatic brain injury using human iPSC-derived cortical brain organoids
Authors: Lai Jesse D. , Berlind Joshua E. , Fricklas Gabriella , Maria Naomi Sta , Jacobs Russell , Yu Violeta , Ichida Justin K.
Published: July 2020

Traumatic brain injury confers a significant and growing public health burden and represents a major environmental risk factor for dementia. Previous efforts to model traumatic brain injury and elucidate pathologic mechanisms have been hindered by complex interactions between multiple cell types, biophysical, and degenerative properties of the human brain. Here, we use high-intensity focused ultrasound to induce mechanical injury in 3D human pluripotent stem cell-derived cortical organoids to mimic traumatic brain injuryin vitro. Our results show that mechanically injured organoids recapitulate key hallmarks of traumatic brain injury, phosphorylation of tau and TDP-43, neurodegeneration, and transcriptional programs indicative of energy deficits. We present high-intensity focused ultrasound as a novel, reproducible model of traumatic brain injury in cortical organoids with potential for scalable and temporally-defined mechanistic studies.
Validation and Long-Term Follow Up of CD33 Off-Targets Predicted In Vitro and In Silico Using Error-Corrected Sequencing in Rhesus Macaques
Authors: AlJanahi Aisha A. , Lazzarotto Cicera R. , Chen Shirley , Shin Tae-Hoon , Cordes Stefan , Jabara Isabel , Zhou Yifan , Young David , Lee Byung-Chul , Yu Kyung-Rok , Li Yuesheng , Toms Bradley , Tunc Ilker , Hong So Gun , Truitt Lauren L. , Klermund Julia , Kim Miriam Y. , Cathomen Toni , Gill Saar , Tsai Shengdar Q. , Dunbar Cynthia E.
Published: July 2020

The programmable nuclease technology CRISPR/Cas9 has revolutionized gene editing in the last decade. Due to the risk of off-target editing, accurate and sensitive methods for off-target characterization are crucial prior to applying CRISPR/Cas9 therapeutically. Here, we utilized a rhesus macaque model to ask whether CIRCLE-Seq (CS), anin vitrooff-target prediction method, more accurately identifies off-targets compared toin silicoprediction (ISP) based solely on genomic sequence comparisons. We use AmpliSeq HD error-corrected sequencing to validate off-target sites predicted by CIRCLE-Seq and ISP for guide RNAs designed againstTET2andCD33genes. A gRNA targeting TET2 designed using modern algorithms and predicted to have low off-target risk by both ISP and CIRCLE-Seq created no detectable mutations at off-target sites in hematopoietic cells following transplantation, even when applying highly sensitive error-corrected sequencing. In contrast, aCD33gRNA designed using less robust algorithms with over 10-fold more off-targets sites predicted by both ISP and CIRCLE-Seq, however there was poor correlation between the sites predicted by the two methods. When almost 500 sites identified by each method were searched for in hematopoietic cells following transplantation, 19 detectable mutations in off-target sites were detected via error-corrected sequencing. Of these 19 sites, 8 sites were predicted in the top 500 sites by both methods, 8 by CIRCLE-Seq only, and 3 by ISP only. Cells with off-target editing exhibited no expansion or abnormal behaviorin vivoin animals followed for up to 2 years. In conclusion, neither methodology predicted all sites, and a combination of careful gRNA design, followed by screening for predicted off-target sites in target cells by multiple methods may be required for optimizing safety of clinical development.
Decoding 3D spatial location across saccades in human visual cortex
Authors: Zhang Xiaoli , Jones Christopher M , Golomb Julie D
Published: July 2020

Visual signals are initially processed as two-dimensional images on our retina, but we live in a 3D world. Depth information needs to be reconstructed from the 2D retinal images, using cues such as binocular disparity. But in daily life, we also make frequent, rapid eye movements, which alter the 2D retinal input. How do we achieve stable 3D perception across saccades? Using fMRI pattern analysis, we investigated how 3D spatial representations in human visual cortex are influenced by saccades. Participants viewed stimuli in four possible 3D locations, defined by 2D vertical position (above or below screen center) and depth position (in front of or behind central screen plane). We compared the amount of 2D and depth information in visual cortical regions during no-saccade blocks (stationary fixation) with that during saccade blocks (series of guided saccades). On no-saccade blocks, decoding of stimulus location was highlydependenton fixation position: in later visual areas we could decode both vertical and depth information across blocks that shared the same fixation position (as previously reported), but little vertical or depth information could be decoded across blocks withdifferentfixation positions. Strikingly, the neural similarity patterns appearedtolerantto changes in fixation position during saccade blocks: despite the saccade-induced retinal and fixation changes, we could reliably decode both vertical and depth information. The findings suggest that representations of 3D spatial locations may become more tolerant of fixation positions during dynamic saccades, perhaps due to active remapping which may encourage more stable representations of the world.

Significance

This study investigates two fundamental challenges for visual perception: how to preserve spatial information across frequent eye movements, and how to integrate binocular depth location with 2D location to form coherent 3D percepts. Aspects of these challenges have been studied in isolation, but surprisingly no studies have investigated them jointly to ask how 3D spatial representations in human visual cortex are influenced by saccades. Our fMRI pattern analysis findings highlight a potentially critical role of active, dynamic saccades on stabilizing 3D spatial representations in the brain, revealing that representations of 3D space may be modulated by eye position during sustained fixation, but could become tolerant of changes in eye position during active, dynamic saccades.
Crystal forms and phase transformation of 1,5-pentanediamine-terephthalate: a bio-based nylon 5T monomer
Authors: Li Zihan , Yang Pengpeng , Liu Haodong , Liu Jun , Zhu Sha , Li Xiaojie , Zhuang Wei , Wu Jinglan , Ying Hanjie
Published: July 2020

Nylon 5T is one of the bio-based nylons, its raw material 1,5-pentanediamine is derived from biomass resources and produced by biological methods. 1,5-pentanediamine-terephthalate (PDA-TPA) is the monomeric salt for nylon 5T polymerization, and its own product quality has a significant impact on the performance of nylon 5T. PDA-TPA was prepared by anti-solvent crystallization in this study. It exists in two solid forms, a monohydrate [form (I)] and an anhydrous phase [form (II)]. The transition temperature of the two phases was around 65°C in the given ethanol–water binary (7:1) mixture. The characterization of monohydrate and anhydrate phases regarding structures and stabilities was carefully carried out using powder X-ray diffraction, single crystal X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy and Fourier transform infrared spectroscopy. The relationship between the molecular interactions of monohydrate and anhydrate phases under different packing architectures and their thermal behaviours was analysed and established. In addition, the relationships between the structures and thermal behaviours for the two solid forms were analysed and established. In addition, the effect of solvent on phase conversion, the relationships between the temperature and water activity, as well as the relative stability of monohydrate and anhydrate phases under different thermodynamic conditions, were investigated by solid–solid transformation and solvent-mediated transformation experiments. It was obvious that the transition temperature of monohydrate and anhydrate phases of PDA-TPA was significantly influenced by water activity, and the larger the value of water activity is, the higher is the transition temperature. These studies give insight into the transformation of nylon 5T monomer salt and contribute to the control of target crystal preparation.
Variation of cation distribution with temperature and its consequences on thermal expansion for Ca3Eu2(BO3)4
Authors: Kosyl Katarzyna M. , Paszkowicz Wojciech , Shekhovtsov Alexey N. , Kosmyna Miron B. , Antonowicz Jerzy , Olczak Adam , Fitch Andrew N.
Published: July 2020

The structure of calcium europium orthoborate, Ca3Eu2(BO3)4, was determined using high-resolution powder X-ray diffraction data collected at the ID22 beamline (ESRF) under ambient conditions, as well as at high temperature. Rietveld refinement allowed determination of the lattice constants and structural details, including the Ca/Eu ratios at the three cationic sites and their evolution with temperature. Clear thermal expansion anisotropy was found, and slope changes of lattice-constant dependencies on temperature were observed at 923 K. Above this temperature the changes in occupation of the Ca/Eu sites occur, exhibiting a tendency towards a more uniform Eu distribution over the three Ca/Eu sites. Possible structural origins of the observed thermal expansion anisotropy are discussed.
The relationship between Hirshfeld potential and cytotoxic activity: a study along a series of flavonoid and chromanone derivatives
Authors: Małecka Magdalena , Kusz Joachim , Eriksson Lars , Adamus-Grabicka Angelika , Budzisz Elżbieta
Published: July 2020

The present study examines a series of six biologically-active flavonoid and chromanone derivatives by X-ray crystal structure analysis: (E)-3-benzylidene-2-phenylchroman-4-one, C22H16O2, I, (E)-3-(4-methylbenzylidene)-2-phenylchroman-4-one, C23H18O2, II, (E)-3-(3-methylbenzylidene)-2-phenylchroman-4-one, C23H18O2, III, (E)-3-(4-methoxybenzylidene)-2-phenylchroman-4-one, C23H18O3, IV, (E)-3-benzylidenechroman-4-one, C16H12O2, V, and (E)-3-(4-methoxybenzylidene)chroman-4-one, C17H14O3, VI. The cytotoxic activities of the presented crystal structures have been determined, together with their intermolecular interaction preferences and Hirshfeld surface characteristics. An inverse relationship was found between the contribution of C...C close contacts to the Hirshfeld surface and cytotoxic activity against the WM-115 cancer line. Dependence was also observed between the logP value and the percentage contribution of C...H contacts to the Hirshfeld surface.
An overview of the existing problems faced by Pakistani women in agriculture: conclusion and recommendation
Authors: Muhammad Faheem , Hassan Muhammad Azher , Mehmood Tariq
Published: July 2020

Purpose

The purpose of this paper is an attempt to cover available literature on natural resource management, which reflects the involvement of Pakistan communities living in different regions for sustainable management in agriculture, forestry and livestock sectors differentiated by women. In addition, it was also highlighted about the lack of access to productive resources for rural women farmers. The conclusion was drawn and key recommendation were suggested.

Design/methodology/approach

It is authors real-life experiences or observations in a given field to support colleagues in a variety of ways including advising, establishing best practices and noting trends.

Findings

It was concluded that there are no opportunities such as training of most advanced launched technologies for the sake of better crop production, dairy and fisheries sector sustainable development, as well as the availability of microfinance to support the women farmers in Pakistan rural areas to make them self-dependent.

Originality/value

The opinions and key recommendations are genuine and useful, which should be adopted for the more bright future of women farmers, especially in Pakistan’s rural area.
Is there transgender bias in the courtroom?
Authors: Honorée André L. , Juban Rusty
Published: July 2020

Purpose

This study examines whether various judicial demographic and political characteristics have an influence on case outcomes in transgender employment discrimination cases. Specifically, it assesses whether the race, sex or political party of federal judges result in significantly different employment case outcomes for transgender employees in the US district courts.

Design/methodology/approach

Utilizing a legal database of all federal employment discrimination cases over the past five decades, the study ultimately identified 97 cases with transgender plaintiffs. Chi-square and frequency analyses were employed to test the hypotheses regarding the effect of race, sex and political party of federal judges on transgender employment case outcomes.

Findings

The results intimate that both the political party and sex of the judge have an effect on case outcomes. Specifically, the transgender plaintiffs in employment discrimination cases have a greater chance for success when such cases are presided before Democratic and female judges.

Practical implications

The study's findings of significant differences in case outcomes suggest that characteristics of judges should be taken into account by potential plaintiffs and defendants, as they consider if/how to proceed with their cases.

Social implications

Such research focuses more attention on the fair and equal treatment principle of the American judicial system due to the significant differences found in case outcomes as a result of judges' characteristics.

Originality/value

No research till date has examined the outcomes of transgender employment discrimination cases in the US despite national surveys indicating the pervasiveness and severity of such discrimination.
Canada’s emerging foresight landscape: observations and lessons
Authors: Wilner Alex , Roy Martin
Published: July 2020

Purpose

The purpose of this paper is twofold: to introduce scholars and practitioners of foresight to the emerging Canadian foresight ecosystem, and to provide lessons learned on developing policy foresight from the Government of Canada context.

Design/methodology/approach

The paper provides a series of lessons based in part on informal and indirect observations and engagement with established Canadian foresight entities, including Policy Horizons Canada, and numerous newly established foresight initiatives at Global Affairs Canada, Standards Council of Canada and the Canadian Forest Service.

Findings

The paper finds that Canada’s newly emerging foresight units and initiatives face structural, institutional and organizational challenges to their long-term success, including in concretely measuring foresight outcome (rather than simply output) in policy making.

Originality/value

The paper provides a unique and empirically driven perspective of the foresight ecosystem that has emerged within the Canadian federal public service since 2015. Lessons are culled from this emerging network of Canadian foresight practitioners for international application.