bluuebunny/crossref_metadata_2025 huggingface dataset:
6. COMPARISON OF PATIENT EDUCATION USING NATIVE LANGUAGE AND BAHASA TO TREATMENT COMPLIANCE FOR HYPERTENSIVE PATIENTS IN NORTH TIWORO DISTRICT
Authors: Johan Alvin , Natalia Audrey
Published: May 2021

Background:

Hypertension treatment compliance at the primary care level in Indonesia was around 58%. The language barrier was known to be a potential factor of hypertension treatment non-compliance.

Objective:

To determine whether educating about hypertension to the patients in their native language will improve treatment compliance than educating in Bahasa.

Method:

This was a prospective cohort study. The research was conducted in Tondasi Health Care Center from March 2019 until April 2020. Inclusion criteria were patients with newly diagnosed hypertension and can communicate in Bahasa. The patient was excluded if he/she was reported dead during this study's follow-up period. Good treatment compliance is defined by a follow-up visit to the health care center on the follow-up date that was previously agreed upon with the patients. The data was analyzed using the test of two proportions with a chi-square test of homogeneity on SPSS 24 software.

Result:

We included a total number of 80 hypertensive patients in this study. Education regarding hypertension emphasizing the importance of routine control was given verbally in the patient's native language by a translator to 40 patients. The same education material was given verbally in the Bahasa to the other 40 patients. No patient was excluded from this study. In the native language education group, 22 patients (55%) had a good treatment compliance compared to 12 patients (30%) in the Bahasa education group, a statistically significant difference in the proportion of 0.25, p = 0.024.

Conclusion:

Educating patients in their native language results in better hypertension treatment compliance.
11. PREVALENCE OF HYPERTENSIVE HEART DISEASE COMPARED TO CORONARY ARTERY DISEASE BASED ON ECHOCARDIOGRAPHY FINDINGS IN BANDUNG REGIONAL PUBLIC HOSPITAL FROM SEPTEMBER 2020-DECEMBER 2020
Authors: Cahyono Alvin Eliata , Rostiati Dini
Published: May 2021

Background:

Hypertension was defined as SBP 140 mmHg and/or DBP 90 mmHg. The prevalence according to Indonesia Family Life Survey-5, among males and females were 31.0% and 35.4%. Hypertension could cause cardiac manifestations, including Hypertensive Heart Disease (HHD) and Coronary Artery Disease (CAD). HHD was a heart response to the afterload burden on the left ventricle caused by the progression of arterial pressure and total peripheral resistance, characterized by increased left ventricular mass associated with left ventricular hypertrophy (LVH), which was recommended echocardiography by ESH/ESC 2013 Guideline. This research was conducted to find out the prevalence of HHD compared to CAD based on echocardiography in Bandung Regional Public Hospital.

Methods:

This is a descriptive study. We conducted a search of echocardiograph from all inpatients and outpatients that came first time to the cardiology clinic, from September 2020-December 2020. The patients included all gender and age. Data collected included Posterior Wall (PW) thickness, Inter Ventricular Septum (IVS) thickness and Left Ventricle Ejection Fraction (LVEF). LVH was defined if the PW or IVS thickness was greater than 11 mm as measured by M-mode echocardiography. LVH with LVEF >55% was interpreted as HHD.

Results:

A total of 205 patients were analyzed. There were 75 (36.58%) diagnosed with HHD, 81 (39.52%) diagnosed with CAD, and 49 (23.90%) diagnosed with others. From 75 patients with HHD, 36 (48%) were males and 39 (52%) were females.

Conclusion:

The prevalence of HHD was 36.58%, with 48% males and 52% females. This study matched with the IFLS-5 findings.
13. GARLIC EFFECT ON REDUCE BLOOD PRESSURE AND CHOLESTEROL IN PATIENTS WITH AND WITHOUT HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Mulawarman Rido , Trifitriana Monica , Felani Muhammad Rizky , Mulawarman  , Tondas Alexander Edo
Published: May 2021

Background:

Garlic has been linked to improved cardiovascular health. Garlic has been suggested to lower blood pressure, plasma lipids as well as an antiplatelet effect and other cardiovascular markers.

Objective:

We aim to assess the latest evidence on the effect of garlic on blood pressure and cholesterol in patients with and without hypertension through systematic review and meta-analysis.

Method:

We performed a comprehensive search on topics that assesses garlic outcomes in patients with and without hypertension from inception up until December 2020.

Results:

There were a total of 503 patients from 12 controlled trial studies. Pooled systolic blood pressure was lower in garlic group (mean difference -3.62 [-5.43, -1.80], p = <0.000001; I
2: 85%, p < 0.0001). Meta-analysis showed that diastolic blood pressure was lower in garlic group (mean difference -1.40 [-2.72, -0.08], p = <0.00001; I
2: 86%, p = 0.04) on follow-up. Total cholesterol was also lower in garlic group (mean difference -17.17 [-28.57, -5.78], p < 0.00001; I
2: 86%, p = 0.003). Level of heart rate was similar in garlic and placebo group.

Conclusion:

This meta-analysis suggests that garlic is associated with reducing blood pressure and cholesterol in patients with and without hypertension. Future long-term trials are needed to elucidate the impact of garlic on cardiovascular morbidity and mortality.
40. THE RELATION BETWEEN INTERDIALYTIC WEIGHT GAIN AND INTRADIALYTIC HYPERTENSION IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH ROUTINE HEMODIALYSIS IN PROF. DR. R.D. KANDOU GENERAL HOSPITAL MANADO
Authors: Natalia Cynthia , Sugeng Cerelia , Umboh Octavianus , Palar Stella
Published: May 2021

Background:

Chronic kidney disease (CKD) is a pathological process hallmarked by progressive decline of kidney function and most likely end up in kidney failure state. Hemodialysis (HD) is one of the main therapy for CKD, where the goal is to replace renal function in maintaining fluid and acid-base-electrolyte balance, excreting metabolism waste and controlling blood pressure. Intradialytic hypertension (IDH) is a possible complication during HD. Interdialytic Weight Gain (IDWG) is a risk factor of IDH.

Objective:

To acknowledge relation between IDWG and IDH incidence in CKD patients.

Method:

This is analytic observational cross sectional study that was carried out from November–December 2020. Patients with CKD aged ≥18 years old and had routine HD twice a week for at least 3 months. IDWG = [(current pre dialysis weight – previous post dialysis weight)/dry weight × 100%]. Dry weight was defined by body weight without clinical sign of fluid retention. IDWG were categorized into 3 groups: <3% (group I); 3.1–3.9% (group II); >3.9% (group III). IDH was defined by increasing in systolic blood pressure >10 mmHg after at least 4 of 6 consecutive HD sessions. Blood pressure was measured 30 minutes before and after HD. Patients who did not finish at least 4 HD sessions, refused informed consent, and whose body weight unobtainable were excluded. Data was analyzed using chi square with significance level of p < 0.05 and confidence interval (CI) 95%.

Result:

140 patients were included in this study (70 male, 70 female). IDH were found in all 3 IDWG groups: group I 37%, group II 80%, and group III 93.1%. Data analysis showed a significant relation between IDWG and IDH (p = 0.0001).

Conclusion:

There is a significant relation between IDWG and incidence of IDH.
46. ASSOCIATION OF LOW-CARBOHYDRATE DIETARY HABIT AND BLOOD PRESSURE
Authors: Harlyjoy Beta Canina , Widyantoro Bambang , Sukmawan Renan
Published: May 2021

Background:

Hypertension is a major risk factor for cardiovascular events. Several studies have shown dietary modification as one of the cornerstones in the non-pharmacological intervention in patients with hypertension. Alas, the recommended macronutrients diet is still at dispute.

Objective:

This study aimed to observe the association between the macronutrient components of dietary habit and blood pressure.

Methods:

This study was conducted in the district of Natuna, in July 2019. Dietary habit was obtained through food recall, on which each patient was thoroughly interviewed regarding their food consumption for 2 days, 1 representing weekday and 1 for the weekend. Blood pressure reading was taken 3 times, with the hypertension status was determined by the average of 2nd and 3rd readings.

Results:

Two hundred and one patients were included in this study. In our populations, the hypertension rate was 78.6%. Those with hypertension showed lower energy intake (1026: 313–3547 vs 1070: 430–3348 calories per day, p = 0.651), lower protein intake (0.65: 0.20–4.89 vs 0.75: 0.21–2.61 g/kg body weight, p = 0.238), higher fat intake (20.55 ± 7.66 vs 19.6 ± 7.37% of calories intake, p = 0.691), and slightly lower carbohydrate intake (61.56 ± 10.4 vs 61.58 ± 8.5% of calories intake, p = 0.641). Chi-square analysis found that carbohydrate intake more than 45% of daily calories was associated with hypertension (p = 0.039) with odds ratio of 4.026, 95% CI of 1.109–14.619 (p = 0.034).

Conclusion:

Carbohydrate intake more than 45% of daily calories intake is associated with hypertension.
50. BLOOD PRESSURE AT ADMISSION AS A PREDICTOR OF INCREASED LEFT VENTRICULAR EJECTION FRACTION WITHIN 1-YEAR FOLLOW-UP IN PATIENTS HOSPITALIZED FOR ACUTE HEART FAILURE
Authors: Khaerani Ayu S. , Widyantoro Bambang
Published: May 2021

Background:

Patients present with the improvement of left ventricular ejection fraction (LVEF) had favorable outcomes than those who maintain systolic dysfunction. Acute heart failure is a rapid development of worsening symptoms and signs of heart failure.

Objective:

We sought any predictors to improve ejection fraction, particularly those who were admitted with an acute heart failure condition.

Method:

Data from a total of 20772 patients admitted to our center from January to December 2019 were collected retrospectively from electronic medical records. Patients <18 years old who were diagnosed with chronic heart failure and previously had medical treatment in our center, no echocardiography follow-up results, and moderate-severe valvular heart disease were excluded. Patients with LVEF < 40% at admission and had LVEF ≥ 40% within 1-year follow-up considered as significant increase of ejection fraction.

Result:

Intra-hospital mortality of acute heart failure was 6.3%. Among 134 patients that met our criteria, 29.9% were aged ≥60 years old, 77.6% were males, and 69.4% had hypertension. Echocardiography follows up mostly done after 3 months. Intra-hospital treatment such as revascularization, continued by outpatient treatment such as acetylsalicylic acid, P2Y12-inhibitor, ACE-inhibitor, ivabradine, angiotensin-receptor blocker, beta-blocker, mineralocorticoid-receptor antagonist, nitrates, and HMG-CoA-reductase drugs were not related, meanwhile, higher diastolic blood pressure (p = 0.035) and mean arterial pressure (p = 0.049) at admission were related.

Conclusion:

Diastolic blood pressure and mean arterial pressure were related to the improvement of ejection fraction. This may imply a recovery process of myocardial viability and systolic function by increasing perfusion and blood pressure. Further research is needed to elaborate on this result.
51. ENHANCED EXTERNAL COUNTERPULSATION REDUCES BLOOD PRESSURE IN REFRACTORY ANGINA PECTORIS PATIENTS; A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tarsidin Najmi Fauzan , Tiksnadi Badai Bhatara
Published: May 2021

Refractory angina patients often coexist with hypertension. Uncontrolled hypertension increased the risk of major adverse cardiac event (MACE) and target-organ damage. Enhanced External Counterpulsation (EECP) is a non-invasive treatment that is beneficial in refractory angina pectoris patients. Hemodynamic benefits of EECP to peripheral blood pressure are observed but not yet established. We systematically review the available evidence of the efficacy of EECP in addressing systolic and diastolic blood pressure (SBP and DBP) in refractory angina pectoris patients. We conducted a literature search in MEDLINE and ResearchGate from its inception to January 2021. We included studies that reported SBP and DBP measurement at baseline and after EECP treatment in refractory angina patients. We conducted a meta-analysis of weighted mean differences from baseline to post-intervention for SBP and DBP. We identified 22 studies from 17 articles (n = 1564) consisting of 12 articles EECP only and six articles EECP vs control. Within EECP group, EECP treatment significantly reduce SBP by 6.7 mmHg (MD −6.77, 95%CI −9.09 to −4.45, p = <0.00001, I
2 = 71%) and DBP by 3 mmHg (MD −3.03, 95%CI −4.07 to −2, p = <0.00001, I
2 = 49%). Between-group, EECP treatment compared to control could reduce SBP by 9.1 mmHg (MD −9.15, 95%CI −15.75 to −2.56, p = 0.007, I
2 = 80%) and SBP by 2.6 mmHg (MD −2.68, 95%CI −5.52 to −0.17, p = 0.07, I
2 = 63%). Conclusion: EECP treatment provides additional benefits that reduce SBP and DBP in refractory angina pectoris patients to support controlling hypertension and reduce the risk of MACE and target-organ damage.
53. LV FILLING PRESSURE IN PATIENT WITH HYPERTENSIVE HEART DISEASE
Authors: Widyastuti Wenny , Yanni Mefri , Maulana Giovanno R
Published: May 2021

Background:

Patient with Hypertensive Heart Disease (HHD) could develop asymptomatic LV dysfunction, and when LV diastolic function is impaired, the patient could have heart failure even with preserved LV ejection fraction. Assessment of left ventricular filling pressure is indicator of LV diastolic dysfunction in HHD patients.

Objective:

To evaluate LV filling pressure of HHD patient in outpatient clinic of M. Djamil Hospital Padang.

Methods:

We collect data of 170 HHD patients during 2018–2019 who met inclusion criteria. Subject were categorized based on LV geometric pattern. LV filling pressure was determined from mitral velocity inflow (E/A ratio) and left atrial volume index (LAVI). Statistical analysis was performed using SPSS.

Results:

Most subject were female (n = 52.9%), mean age was 59.06 ± 10.5 years and no significant difference of age between groups (p = 0.36). The most LV geometric pattern was LV concentric hypertrophy (CH) (n = 60.58%). Only 10.6% subjects were symptomatic. Mean E/A ratio was 0.94 ± 0.2, highest value was in LV eccentric hypertrophy (EH) group (0.95 ± 0.3), but no significant difference between group (p = 0.603). There was significant difference of LAVI between groups (p = 0,007) with EH group have the highest value (mean 35.2 ± 12.0 ml/m2). No difference of diastolic dysfunction (p = 0.42).

Conclusion:

Majority of subject in this study were asymptomatic and have CH geometric pattern. LV filling pressure was not showed significantly from E/A ratio analysis. There was significant difference of LAVI with EH group have more higher LAVI value that showed increased LV filling pressure.
Renal Normothermic Machine Perfusion: The Road Toward Clinical Implementation of a Promising Pretransplant Organ Assessment Tool
Authors: Hamelink Tim L. , Ogurlu Baran , De Beule Julie , Lantinga Veerle A. , Pool Merel B.F. , Venema Leonie H. , Leuvenink Henri G.D. , Jochmans Ina , Moers Cyril
Published: May 2021

The increased utilization of high-risk renal grafts for transplantation requires optimization of pretransplant organ assessment strategies. Current decision-making methods to accept an organ for transplantation lack overall predictive power and always contain an element of subjectivity. Normothermic machine perfusion (NMP) creates near-physiological conditions, which might facilitate a more objective assessment of organ quality before transplantation. NMP is rapidly gaining popularity, with various transplant centers developing their own NMP protocols and renal viability criteria. However, to date, no validated sets of on-pump viability markers exist nor are there unified NMP protocols. This review provides a critical overview of the fundamentals of current renal NMP protocols and proposes a framework to approach further development of ex vivo organ evaluation. We also comment on the potential logistical implications of routine clinical use of NMP, which is a more complex procedure compared with static cold storage or even hypothermic machine perfusion.
The OPRD1 rs678849 variant influences outcome of disulfiram treatment for cocaine dependency in methadone-maintained patients
Authors: Thomas Patrick S. , Nielsen Ellen M. , Spellicy Catherine J. , Harding Mark J. , Ye An , Patriquin Michelle , Hamon Sara C. , Kosten Thomas R. , Nielsen David A.
Published: May 2021

Objective

Prior research demonstrated that the δ-opioid receptor (OPRD1) rs678849 variant influences opioid use in African Americans treated with methadone. We examined whether this variant moderated cocaine and opioid use in our clinical cohort of methadone and disulfiram treated recipients.

Methods

Cocaine and opioid codependent patients were stabilized for 2 weeks on methadone and subsequently randomized into groups treated with either methadone + placebo (n = 37) or methadone + disulfiram (250 mg/day; n = 33) for 12 weeks.

Results

A drop in cocaine-positive urine was found in the OPRD1 CC genotype group compared to T-allele carrier patients treated with methadone + disulfiram (P < 0.0001), but not in the methadone + placebo group. No difference in opioid-positive urines was found among each genotype group in either treatment group.

Conclusion

These findings suggested that rs678849 genotype may predict treatment response of disulfiram for cocaine use in patients with co-occurring opioid and cocaine dependence.
Effect of the ridge position ratio on the thermal environment of the Chinese solar greenhouse
Authors: Wu Xiaoyang , Liu Xingan , Yue Xiang , Xu Hui , Li Tianlai , Li Yiming
Published: May 2021

This paper clarified the mechanism of the south and north roofs' effect on the thermal environment of the Chinese solar greenhouse (CSG), using a new parameter: ridge position ratio (RPR), which can describe the dynamic dependency relationship between the south and north roofs. A mathematical model was established using a method of combining computational fluid dynamics (CFD) simulation with experiments, then the model was used to further analyse the effect of RPR on the thermal environment of the CSG. The experimental greenhouse was simulated as an empty building to obtain results independently from these factors including crop and ventilation conditions. The results showed that the occurrence time of the maximum air temperature will be delayed when RPR increases to 0.3 during the daytime. As RPR increases, the heat storage layer of the soil gradually becomes thinner, but the north wall remains unchanged. RPR has a relatively small effect on the minimum temperature of each greenhouse part during the night. Mathematical models of the relationships between RPR, the solar energy that entered the greenhouse and the released heat energy of the enclosure structures were established, respectively. This paper can provide theoretical guidance for the structural design of the CSG.
Application of Hantzsch reaction for sensitive determination of eflornithine in cream, plasma and urine samples
Authors: Almahri Albandary , Abdel-Lateef Mohamed A.
Published: May 2021

Eflornithine (EFN) is an anti-
Trypanosoma brucei
agent for the medication of sleeping sickness and widely distributed for the treatment of hirsutism (unwanted facial hair in women). The presented work demonstrates a comprehensive analytical approach for the spectrofluorometric determination of EFN in commercial cream samples and various biological samples. The proposed method is based on the formation of a highly yellow–green fluorescence dihydropyridine derivative after the interaction between EFN and acetylacetone/formaldehyde reagent in a slightly acidic medium. Furthermore, the optimal variables such as reagent volumes, pH of the medium, heating time, buffer volume, heating temperature and diluting solvent were carefully selected to achieve the maximum fluorescence activity. The fluorescence activity for the formed derivative was measured at
λ
emission
= 477 nm after
λ
excitation
= 418 nm. Concerning linearity, accuracy, sensitivity, precision and robustness, the presented method was validated and verified according to ICH guidelines. Moreover, the proposed work offered a selective determination for EFN in various brands of pharmaceutical cream without any interference from excipients. Eventually, the current approach was assured to be successful in the estimation of EFN in urine and plasma samples with acceptable recovery results.
Exploring the phylogeography and population dynamics of the giant deer (
Megaloceros giganteus
) using Late Quaternary mitogenomes
Authors: Rey-Iglesia Alba , Lister Adrian M. , Campos Paula F. , Brace Selina , Mattiangeli Valeria , Daly Kevin G. , Teasdale Matthew D. , Bradley Daniel G. , Barnes Ian , Hansen Anders J.
Published: May 2021

Late Quaternary climatic fluctuations in the Northern Hemisphere had drastic effects on large mammal species, leading to the extinction of a substantial number of them. The giant deer (
Megaloceros giganteus
) was one of the species that became extinct in the Holocene, around 7660 calendar years before present. In the Late Pleistocene, the species ranged from western Europe to central Asia. However, during the Holocene, its range contracted to eastern Europe and western Siberia, where the last populations of the species occurred. Here, we generated 35 Late Pleistocene and Holocene giant deer mitogenomes to explore the genetics of the demise of this iconic species. Bayesian phylogenetic analyses of the mitogenomes suggested five main clades for the species: three pre-Last Glacial Maximum clades that did not appear in the post-Last Glacial Maximum genetic pool, and two clades that showed continuity into the Holocene. Our study also identified a decrease in genetic diversity starting in Marine Isotope Stage 3 and accelerating during the Last Glacial Maximum. This reduction in genetic diversity during the Last Glacial Maximum, coupled with a major contraction of fossil occurrences, suggests that climate was a major driver in the dynamics of the giant deer.
Transgenerational fitness effects of lifespan extension by dietary restriction in
Caenorhabditis elegans
Authors: Ivimey-Cook Edward R. , Sales Kris , Carlsson Hanne , Immler Simone , Chapman Tracey , Maklakov Alexei A.
Published: May 2021

Dietary restriction (DR) increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here, we investigated the effect of DR by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in
Caenorhabditis elegans
. We show that while TF robustly reduces mortality risk and improves late-life reproduction of the individuals subject to TF (P
0
), it has a wide range of both positive and negative effects on their descendants (F
1
–F
3
). Remarkably, great-grandparental exposure to TF in early life reduces fitness and increases mortality risk of F
3
descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of DR, underscoring the need to consider fitness of future generations in pursuit of healthy ageing.
Seizure Forecasting Using a Novel Sub-Scalp Ultra-Long Term EEG Monitoring System
Authors: Stirling RE , Karoly PJ , Maturana MI , Nurse ES , McCutcheon K , Grayden DB , Ringo SG , Heasman J , Cameron TL , Hoare RJ , Lai A , D’Souza W , Seneviratne U , Seiderer L , McLean KJ , Bulluss KJ , Murphy M , Brinkmann BH , Richardson MP , Freestone DR , Cook MJ
Published: May 2021

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG.

Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder™), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilising cycles in EA and previous seizure times.

The procedures and devices were well tolerated, and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88) is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.
Characterization of direct and/or indirect genetic associations for multiple traits in longitudinal studies of disease progression
Authors: Brossard Myriam , Paterson Andrew D. , Espin-Garcia Osvaldo , Craiu Radu V. , Bull Shelley B.
Published: May 2021

When quantitative longitudinal traits are risk factors for disease progression and subject to random biological variation, joint model analysis of time-to-event and longitudinal traits can effectively identify direct and/or indirect genetic association of single nucleotide polymorphisms (SNPs) with time-to-event. We present a joint model that integrates:i)a multivariate linear mixed model describing trajectories of multiple longitudinal traits as a function of time, SNP effects, and subject-specific random effects, andii)a frailty Cox survival model that depends on SNPs, longitudinal trajectory effects, and subject-specific frailty accounting for dependence among multiple time-to-event traits. Motivated by complex genetic architecture of type 1 diabetes complications (T1DC) observed in the Diabetes Control and Complications Trial (DCCT), we implement a two-stage approach to inference with bootstrap joint covariance estimation and develop a hypothesis testing procedure to classify direct and/or indirect SNP association with each time-to-event trait. By realistic simulation study, we show that joint modelling of two time-to-T1DC (retinopathy, nephropathy) and two longitudinal risk factors (HbA1c, systolic blood pressure) reduces estimation bias in genetic effects and improves classification accuracy of direct and/or indirect SNP associations, compared to methods that ignore within-subject risk factor variability and dependence among longitudinal and time-to-event traits. Through DCCT data analysis, we demonstrate feasibility for candidate SNP modelling, and quantify effects of sample size and Winner’s curse bias on classification for two SNPs identified as having indirect associations with time-to-T1DC traits. Overall, joint analysis of multiple longitudinal and multiple time-to-event traits provides insight into complex trait architecture.
Validation of a multi-gene qPCR-based pharmacogenomics panel across major ethnic groups in Singapore and Indonesia
Authors: Kothary Anar Sanjaykumar , Mahendra Caroline , Tan Mingchen , Min Tan Eunice Jia , Hong Yi Jacelyn Phua , Gabriella  , Hui Jocelyn Tan Xin , Haruman Jessline Stephanie , Tan Zhihao , Lee Chun Kiat , Lezhava Alexander , Yan Benedict , Irwanto Astrid
Published: May 2021

Background

With up to 70% of adverse drug reactions (ADRs) having high genetic associations, the clinical utility of pharmacogenomics (PGx) has been gaining traction. Nala PGx Core™ is a multi-gene qPCR-based panel that comprises 18 variants and 2 CYP2D6 Copy Number markers across 4 pharmacogenes – CYP2C9, CYP2C19, CYP2D6 and SLCO1B1.

Objectives

In this study, we validated the performance of Nala PGx Core™ against benchmark methods, on the Singaporean and Indonesian populations. Additionally, we examined the allele and diplotype frequencies across 5 major ethnic groups present in these populations namely, Indonesians, Chinese, Malays, Indians and Caucasians.

Methods

Human gDNA samples, extracted from the buccal swabs of 246 participants, were tested on Nala PGx Core™ and two chosen benchmarks, Agena VeriDose® Core and CYP2D6 Copy Number Variation (CNV) Panel, and TaqMan® DME Genotyping Assays. Performance was evaluated based on assay robustness, precision and accuracy at the genotype- and diplotype-level.

Results

Nala PGx Core™ demonstrated high genotype- and diplotype-level call rates of >97% and >95% respectively in CYP2D6, and 100% for CYP2C9, CYP2C19 and SLCO1B1. A precision rate of 100% was observed on both intra- and inter-precision studies. Variant-level concordance to the benchmark methods was ≥96.9% across all assays, which consequently resulted in a diplotype-level concordance of ≥94.7% across CYP2C9, CYP2C19 and CYP2D6. Overall, the allele frequencies of CYP2D6*10 and CYP2D6*36 were higher in our cohort as compared to previous records. Notably, CYP2D6 copy number variation (CNV) analysis demonstrated a CYP2D6 *10/*36 frequency of 26.5% amongst the Indonesian cohort.

Conclusion

Nala PGx Core™ produced robust and accurate genotyping when compared to other established benchmarks. Furthermore, the panel successfully characterized alleles of clinical relevance in the Singaporean and Indonesian populations such as CYP2D6*10 and CYP2D6*36, suggesting its potential for adoption in clinical workflows regionally.
Spontaneous control of SIV replication does not prevent immune dysregulation and bacterial dissemination in animals co-infected withM. tuberculosis
Authors: Moriarty Ryan V. , Rodgers Mark A. , Ellis Amy L. , Balgeman Alexis J. , Larson Erica C. , Hopkins Forrest , Chase Michael R. , Maiello Pauline , Fortune Sarah M. , Scanga Charles A. , O’Connor Shelby L.
Published: May 2021

Individuals infected with both HIV andMycobacterium tuberculosis(Mtb) are more likely to develop severe Tuberculosis (TB) disease than HIV-naïve individuals. To understand how a chronic pre-existing Simian immunodeficiency virus (SIV) infection impairs the early immune response to Mtb, we used the Mauritian cynomolgus macaque (MCM) model of SIV/Mtb co-infection. We examined the relationship between peripheral viral control and Mtb burden, Mtb dissemination, and immunological function between SIV+ spontaneous controllers, SIV+ non-controllers, and SIV-naïve MCM who were challenged with a barcoded Mtb Erdman strain and necropsied six weeks post infection. Mycobacterial burden was highest in the SIV+ non-controllers in all assessed tissues. In lung granulomas, we found the frequency of CD4+ T cells producing TNFα was reduced in all SIV+ MCM, but CD4+ T cells producing IFNγ were only lower in the SIV+ non-controllers. Further, while all SIV+ MCM had more PD1+ and TIGIT+ T cells in the lung granulomas relative to SIV-naïve MCM, SIV+ controllers exhibited the highest frequency of cells expressing these markers. To measure the effect of SIV infection on within-host bacterial dissemination, we sequenced the molecular barcodes of Mtb present in each tissue and characterized the complexity of the Mtb populations. While Mtb population complexity was not associated with infection group, lymph nodes had increased complexity when compared to lung granulomas across all groups. These results provide evidence SIV+ animals, independent of viral control, exhibit dysregulated immune responses and enhanced dissemination of Mtb, likely contributing to the poor TB disease course across all SIV/Mtb co-infected animals.

Importance

HIV and TB remain significant global health issues, despite the availability of treatments. Individuals with HIV, including those who are virally suppressed, are at an increased risk to develop and succumb to severe TB disease when compared to HIV-naïve individuals. Our study aims to understand the relationship between SIV replication, mycobacterial growth, and immunological function in the tissues of co-infected Mauritian cynomolgus macaques during the early phase of Mtb infection. Here we demonstrate that increased viral replication is associated with increased bacterial burden in the tissues and impaired immunologic responses, and that the damage attributed to virus infection is not fully eliminated when animals spontaneously control virus replication.
Lack of evidence for infectious SARS-CoV-2 in feces and sewage
Authors: Albert Sandra , Ruíz Alba , Pemán Javier , Salavert Miguel , Domingo-Calap Pilar
Published: May 2021

Purpose

The SARS-CoV-2 coronavirus is a respiratory virus whose primary route of transmission is airborne. However, it has been shown that the virus can replicate in gastrointestinal cells, can be excreted in feces, and can reach sewage systems. Although viral RNA has been found in patient feces and sewage, little is known about the potential fecal-oral transmission of the coronavirus. Determining the presence of infective viral particles in feces and sewage is necessary to take adequate control measures and to discover new routes of coronavirus transmission.

Methods

Feces and urine of COVID-19 patients, and wastewater samples at the time of high prevalence in the region under study (Valencia, Spain), have been analyzed both by molecular methods and cell culture.

Results

Presence of SARS-CoV-2 in feces of COVID-19 patients has been detected, even in patients without gastrointestinal symptoms, suggesting that viral shedding though stool is common. In addition, we have developed a sample concentration methodology that allows us to maintain the infectivity of the viral particles present in the samples. Finally, inoculation of cell cultures with fecal and sewage concentrated samples do not evidence the presence of infective viral particles.

Conclusion

There is no evidence of the presence of infectious SARS-CoV-2 in feces and sewage, suggesting that fecal-oral transmission is not a primary route. However, larger-scale efforts are needed to elucidate whether the fecal-oral transmission should be considered, especially with the emergence of new viral variants.
A quantitative home-use framework for assessing fertility and identifying novel hormone trends by recording urine hormones
Authors: Pattnaik Siddharth , Das Dipankar , Venkatesan Varun Akur
Published: May 2021

Fertility testing using urinary hormones has been used to effectively improve the likelihood of pregnancy. To provide fertility scores, the existing home-use systems measure one or two hormones. However, the hormone profiles vary depending on cycle duration, fertility-related disorders, drugs and other treatments. Here, we introduce Inito, a mobile-phone connected reader that is scalable to multiple hormone tests. In this report, we assess the accuracy of the quantitative home-based fertility monitor, the Inito Fertility Monitor (IFM), and suggest using IFM as a device to monitor and analyse female hormone patterns. There were two aspects of the study: i. evaluation of the efficacy of IFM in quantifying urinary Estrone-3-glucuronide (E3G), pregnanediol glucuronide (PdG) and luteinizing hormone (LH), and ii. A retrospective study of patients’ hormone profiles using IFM. We observed that with all three hormones, IFM had an accurate recovery percentage and had a CV of less than 10 percent. Furthermore, in predicting the concentration of urinary hormones, IFM showed a high correlation with ELISA. Using Inito in clinical trials, we report a novel criterion for earlier confirmation of ovulation compared to existing criteria. We also present a novel hormone pattern consistent across most menstrual cycles included in the study. In conclusion, the Inito Fertility Monitor is an effective tool for calculating the urinary concentrations of E3G, PdG and LH and can also be used to provide accurate fertility scores and confirm ovulation. In addition, the sensitivity of IFM facilitates the monitoring of menstrual cycle-related hormone patterns, therefore also making it a great tool for physicians to track the hormones of their patients.
Post Operative Pain Management (POPM) and Patient Satisfection : A Tertiary Care Hospital Experience
Authors: Ferdoush Jannatul , Chowdhury Rajib Pal , Johora Fatema , Jeenia Fatiha Tasmin , Ata Maliha , Parveen Kohinoor , Towfiq Hossain Sharif Mohammad , Sharmeen Shagorika , Rahman MD Sayedur
Published: May 2021

Background

Pain is an inevitable part of the postoperative experience. Current study was designed to assess the pattern of analgesic use, the adequacy of post operative pain control by documenting pain scores, and patient satisfaction by documenting the pain perception score of the postoperative patients 48 hours after surgery.

Materials and methods

This was a formative research and includes a mix of descriptive cross-sectional study carried out in the department of Gynecology and Obstetrics, General surgery, and Orthopedics surgery of Chattagram Maa -O- Shishu Hospital Medical College (CMOSHMC) during the month of January, 2018 to July, 2019.

Result

A total of 180 patients undergoing surgery were included in this study. Baseline data were collected both retrospectively and prospectively. Only analgesic used immediately after operation in three departments were Pethidine (100%). Diclofenac sodium suppository were used in appendectomy and cesarean section (50/60, 83%) and (26/60, 43%) respectively. Mostly, Diclofenac Sodium IV (55/60, 91%) was used in lower limb surgery. The maximum pain score were 5.3 (SD=2.3), 5.6 (SD =1.9), and 6.1 (SD =1.3) during coughing in the first 8 hour and minimum pain score 2.4 (SD =1.0), 2.2 (SD = 0.8) and 1.7 (SD=1.3) at rest 48 hours after cesarean section, appendectomy and lower limb surgery respectively. But pain score eventually increased during coughing 48 hours after surgery. After 48 hours of surgery maximum pain perception score 3.9 (SD = 0.9) in lower limb surgery and minimum perception score were 3.5 (SD =1.8) in cesarean section. Majority of the appendectomy patient (76%) satisfied with pain management where as only 43% satisfied in case of cesarean section.

Conclusion

This study enabled the researchers to get a precise picture of the current state of POPM in different hospitals, as well as identify particular needs for improving such practices in health care facilities and implementing an educational intervention in order to improve the post operative pain management.
Simultaneous Morphology, Motility and Fragmentation Analysis of Live Individual Sperm Cells for Male Fertility Evaluation
Authors: Ben-Yehuda Keren , Mirsky Simcha K. , Levi Mattan , Barnea Itay , Meshulach Inbal , Kontente Sapir , Benvaish Daniel , Cur-Cycowicz Rachel , Nygate Yoav N. , Shaked Natan T.
Published: May 2021

We present a new technique for sperm analysis on individual unstained live cells, measuring DNA fragmentation, morphology with virtual staining, and motility. The method relies on quantitative stain-free interferometric imaging and deep-learning frameworks, and is utilized for male fertility evaluation. In the common clinical practice, only motility evaluation is carried out on live human cells, while full morphological evaluation and DNA fragmentation assays require different staining protocols, and therefore cannot be performed on the same cell, resulting in inconsistencies in fertility evaluation. We use a clinic-ready interferometric module to acquire dynamic sperm cells without chemical staining, and deep learning to evaluate all three scores per cell. We show that the number of cells that pass each criterion separately does not accurately predict how many would pass all criteria. This stain-free evaluation method is expected to decrease uncertainty in infertility diagnosis, increasing treatment success rates.
Microbiome dysbiosis regulates the level of energy production under anaerobic condition
Authors: Rahman M. Shaminur , Hoque M. Nazmul , Puspo Joynob Akter , Islam M. Rafiul , Das Niloy , Siddique M. Anwar , Hossain M. Anwar , Sultana Munawar
Published: May 2021

The microbiome of the anaerobic digester (AD) regulates the level of energy production. To assess the microbiome dysbiosis in different stages of anaerobic digestion, we analyzed 16 samples dividing into four groups (Group-I = 2; Group-II = 5; Group-III = 5 and Group-IV = 4) through whole metagenome sequencing (WMS). The physicochemical analysis revealed that highest CH4 production (74.1%, on Day 35 of digestion) was associated with decreased amount of non-metal (phosphorus and sulfur) and heavy metals (chromium, lead and nickel). The WMS generated 380.04 million reads mapped to ~ 2800 distinct bacterial, archaeal and viral genomes through PathoScope (PS) and MG-RAST (MR) analyses. The PS analysis detected 768, 1421, 1819 and 1774 bacterial strains in Group-I, Group-II, Group-III and Group-IV, respectively which were represented by Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes and Fibrobacteres (> 93.0% of the total abundances). The archaeal fraction of the AD microbiomes was represented by 343 strains, of which 95.90% strains shared across these metagenomes. The indicator species analysis showed that Methanosarcina vacuolate, Dehalococcoides mccartyi, Methanosarcina sp. Kolksee and Methanosarcina barkeri were the highly specific for energy production in Group-III and Group-IV. However, most of the indicator phylotypes displayed reduced abundance in the initial stage of biogas production (Group-I and Group-II) compared to their increased relative abundances in Group-IV (Day 35). The correlation network analysis showed that different strains of Euryarcheota and Firmicutes phyla were associated with highest level (74.1%) of energy production (Group-IV). In addition to taxonomic dysbiosis, top CH4 producing microbiomes showed increased genomic functional activities related to one carbon and biotin metabolism, oxidative stress, proteolytic pathways, MT1-MMP pericellular network, acetyl-CoA production, motility and chemotaxis. This study reveals distinct changes in composition and diversity of the AD microbiomes including different indicator species, and their genomic features that are highly specific for energy production.
Retron Editing for Precise Genome Editing without Exogenous Donor DNA in Human Cells
Authors: Kong Xiangfeng , Wang Zikang , Zhou Yingsi , Wang Xing , Shi Linyu , Yang Hui
Published: May 2021

CRISPR-Cas9 mediated seamless genome editing can be achieved by incorporating donor DNA into the CRISPR-Cas9 target loci via homology-directed repair (HDR), albeit with relative low efficiency due to the inefficient delivery of exogenous DNA. Retrons are bacterial genetic element composed of a non-coding RNA (ncRNA) and reverse transcriptase (RT). Retrons coupled with CRISPR-Cas9 have been shown to enhance precise genome editing via HDR in yeast through fusing guide RNA (gRNA) to the 3’ end of retron ncRNA, producing multicopy single-stranded DNA (msDNA) covalently tethered to gRNA. Here, we further engineered retrons by fusing Cas9 with E.coli RT from different clades and joining gRNA at the 5’ end of retron ncRNA, and found that retron editing can achieve precise genome editing efficiently in human cells. By co-expression of Cas9-RT fusions and retron-ncRNA gRNA (rgRNA) in HEK293T cells, we demonstrated the rates of retron editing at endogenous genomic loci was up to 10 %. We expect our retron editing system could aid in advancing the ex vivo and in vivo therapeutic applications of retron.
A Non-redundant Role for T cell-derived IL-22 in Antibacterial Defense of Colonic Crypts
Authors: Zindl Carlene L. , Witte Steven J. , Laufer Vincent A. , Gao Min , Yue Zongliang , Silberger Daniel J. , Harbour Stacey N. , Singer Jeffrey R. , Pham Duy , Moseley Carson E. , Cai Baiyi , Turner Henrietta , Lund Fran E. , Vallance Bruce A. , Rosenberg Alexander F. , Chen Jake Y. , Hatton Robin T. , Weaver Casey T.
Published: May 2021

IL-22 is a key cytokine in immune defense against pathogens at barrier sites. In response to enteric attaching and effacing bacteria, IL-22 produced by type 3 innate lymphoid cells (ILC3s) is thought to be important early for induction of antimicrobial peptides (AMPs) that protect intestinal epithelial cells (IECs) in advance of T cell-derived IL-22 that arises later. Yet, the basis for a requirement for both innate and adaptive IL-22–producing immune cells in protecting the intestinal mucosa is unknown. Here, using novel mice that both report IL-22 expression and can be targeted for its lineage-specific deletion, we show that mice with deficiency of IL-22 targeted to innate immune cells, including ILC3s, have impaired STAT3 activation of surface colonic IECs colonized by bacteria early in infection. In contrast, mice with IL-22 deficiency limited to T cells have complete loss of STAT3 activation in IECs lining colonic crypts and fail to protect the crypts from bacterial invasion late despite ongoing production of IL-22 from ILC3s. T cell-derived IL-22 is required for upregulation of many host-protective genes by crypt IECs, including those encoding AMPs, neutrophil-recruiting chemokines, and mucins and mucin-related molecules, while also restricting pro-inflammatory genes downstream of IFNγ and TNF signals. Thus, T cell-derived IL-22 is indispensable for antibacterial defense and damage control of intestinal crypts.
Modification of D-W model for corrosion rate of shale gas pipeline under the synergistic corrosion of SRB and CO2
Authors: Peng Xingyu , Liu Xinyue
Published: May 2021

Purpose

The purpose of this paper is to develop an equation for the synergistic corrosion of SRB and CO2 based on the D-W model.

Design/methodology/approach

The bacterial types in the a and ß pipelines were studied by the most probable number method, and the corrosion morphology of L360 in pipeline water samples was studied by surface analysis. The corrosion rate of L360 was studied using the weight loss method. The gray correlation method was used to calculate the degree of correlation between the influencing factors of corrosion under the synergistic effect of CO2 and SRB. The curve obtained from PIPESIM software and experiments data was then fitted using multiple non-linear regression method by MATLAB software.

Findings

The equation was used to predict the corrosion of the ß pipeline for verification, and it was found that seven out of ten excavation sites were within a 20% error range.

Originality/value

Using the gray correlation method, an equation that considers synergistic corrosion of SRB and CO2 has been developed based on the D-W model. The equation could be used to predict the corrosion rate of shale gas gathering pipelines through SRB and CO2 synergistic corrosion.