bluuebunny/crossref_metadata_2025 huggingface dataset:
NF90 modulates processing of a subset of human pri-miRNAs
Authors: Grasso Giuseppa , Higuchi Takuma , Mac Victor , Barbier Jérôme , Helsmoortel Marion , Lorenzi Claudio , Sanchez Gabriel , Bello Maxime , Ritchie William , Sakamoto Shuji , Kiernan Rosemary
Published: May 2020

MicroRNAs (miRNAs) are predicted to regulate the expression of >60% of mammalian genes and play fundamental roles in most biological processes. Deregulation of miRNA expression is a hallmark of most cancers and further investigation of mechanisms controlling miRNA biogenesis is needed. The double stranded RNA-binding protein, NF90 has been shown to act as a competitor of Microprocessor for a limited number of primary miRNAs (pri-miRNAs). Here, we show that NF90 has a more widespread effect on pri-miRNA biogenesis than previously thought. Genome-wide approaches revealed that NF90 is associated with the stem region of 38 pri-miRNAs, in a manner that is largely exclusive of Microprocessor. Following loss of NF90, 22 NF90-bound pri-miRNAs showed increased abundance of mature miRNA products. NF90-targeted pri-miRNAs are highly stable, having a lower free energy and fewer mismatches compared to all pri-miRNAs. Mutations leading to less stable structures reduced NF90 binding while increasing pri-miRNA stability led to acquisition of NF90 association, as determined by RNA electrophoretic mobility shift assay (EMSA). NF90-bound and downregulated pri-miRNAs are embedded in introns of host genes and expression of several host genes is concomitantly reduced. These data suggest that NF90 controls the processing of a subset of highly stable, intronic miRNAs.
Comparison of the Accuracy of C1 Pedicle Screw Fixation Using Fluoroscopy and Free-Hand Techniques in Patients With Posterior Arch Thickness of Less Than 4 mm
Authors: Lee Byung-Jou , Kim Myeongjong , Jeong Seong Kyun , Lee Subum , Jeon Sang-Ryong , Roh Sung Woo , Park Jin Hoon
Published: May 2020

BACKGROUND

C1 pedicle screw insertion is not easy, and more fluoroscopy can be required for safe insertion. Fluoroscopy is time consuming and increases patient radiation exposure. There have been no studies comparing the accuracy of C1 pedicle screw insertion using the fluoroscopy and free-hand techniques.

OBJECTIVE

To describe a free-hand C1 pedicle screw insertion method in patients with the posterior arch thickness of less than 4 mm in the thinnest part of the groove, and to compare the clinical and radiological outcomes of C1 pedicle screw insertion using fluoroscopy vs using the free-hand technique.

METHODS

A total of 25 patients who had atlantoaxial instability with a C1 posterior arch <4 mm and were treated with C1 pedicle screw insertion were included. In 10 patients, fluoroscopy was used for C1 pedicle screw insertion, and 15 patients underwent the free-hand technique. We compared the radiologic and clinical outcomes between the 2 groups.

RESULTS

In patients who underwent the free-hand technique, 96.5% of screws were rated as safe (grade A or B), and 80.0% of screws in the fluoroscopy group were rated as safe. Postoperative occipital neuralgia occurred in one patient in the fluoroscopy group and did not occur in the free-hand technique group. There was no significant difference in the improvement of Nurick grade between the 2 groups.

CONCLUSION

C1 pedicle screw insertion using the free-hand technique is feasible and safe in patients with a C1 posterior arch <4 mm.
Men's Decision-Making to Become Nurses
Authors: O'Lynn Chad E. , O'Connor Tom , Herakova Liliana L. , Kellett Peter
Published: May 2020

Patriarchy has been offered as the foundational paradigm for gendered issues in nursing; however, operationalization of this paradigm in order to improve nursing workforce gender diversity is challenging. The qualitative arm of the present study explored men's decision-making to become nurses within a larger gendered context. Findings were then assessed for fit with Gender Role Conflict Theory. Findings suggest that men undergo a process in which contrasting influences are considered. The findings' congruence with gender role conflict theoretical assumptions suggests suitable conceptual fit for male recruitment and retention actions and further research.
The Role of Postoperative Bandage Contact Lens in Patients Undergoing Fasanella-Servat Ptosis Repair
Authors: Adam Robert S. , Harvey John T. , Gould Jonah N. , Suntheralingam Sivisan , Farrokhyar Forough
Published: May 2020

Purpose:

To determine whether a bandage contact lens (BCL) improves patient comfort in the postoperative period in patients undergoing ptosis repair using the Fasanella-Servat technique, compared with no BCL.

Methods:

In this prospective, randomized, double-masked, comparison study, all patients had bilateral Fasanella-Servat surgery. A total of 30 patients were randomized to receive a BCL in one eye and no BCL in the other eye. Patient discomfort was measured as the primary outcome using the Eye Sensation Scale. Blurred vision was measured as a secondary outcome using selected questions from the Ocular Surface Disease Index. The surgeries were performed by 2 surgeons (J.T.H and R.S.A). Outcomes were measured one week following the procedure.

Results:

Patients reported significantly less discomfort in the eye receiving a BCL, with only 13.3% ranking discomfort as “moderate” or “severe,” compared with the eye not receiving BCL, where 63.3% of patients rated discomfort as “moderate” or “severe” (p < 0.001). There was no significant difference in patient-reported blurred vision between the 2 groups (p = 0.520).

Conclusions:

The use of a bandage contact lens after Fasanella-Servat procedure for ptosis repair is recommended as it improves patient comfort. In addition, it has no detrimental effect on patient-reported blurring of vision.
Intraocular lens power calculation in eyes with keratoconus
Authors: Garzón Nuria , Arriola-Villalobos Pedro , Felipe Gema , Poyales Francisco , García-Montero María
Published: May 2020

The purpose was to review and document the methods used to calculate the power of the intraocular lens (IOL) to be implanted in cataract surgery in the specific scenario of eyes with keratoconus. This review included all scientific articles published in English that focused on the parameters and formulas used to calculate the power of the IOL to be implanted in eyes with keratoconus undergoing cataract surgery. There are few publications that show in detail how IOL power is calculated in these particular cases. If the keratometric value used was based on the standard refractive index (1.3375), it resulted in a postoperative refractive error with a tendency to hyperopia. The SRK/T formula yielded the best outcomes. The greater the severity of keratoconus the greater was the deviation of the postoperative refractive status from the target outcome.
A Time-Series Analysis of the Association Between Occupational Health Policies and Opioid Prescription Patterns in United States Active Duty Military Service Members From 2006 to 2018
Authors: Jannace Kalyn C. , Giordano Nicholas A. , Thelus Rosenie , Mukherjee Dhritiman V. , Tilley MAJ Laura , Highland Krista Beth
Published: May 2020

Objective:

The Department of Defense (DoD) implemented numerous occupational health policies to guide opioid prescribing to active duty military service members (ADSM). This retrospective time series analysis evaluated the impact of DoD policies on opioid prescribing trends in ADSM from 2006 to 2018.

Methods:

Bayesian structural time-series models with a Markov chain Monte Carlo algorithm for posterior inference and a semi-local linear trend were constructed to estimate the impact of polices.

Results:

Results indicate annual opioid proportions significantly decreased after the introduction of occupational health policies introduced in 2011 to 2012. Collectively, occupational policies were associated with a significant reduction (6.6%) in annual opioid rates to ADSM following 2012. This observed effect was associated with approximately 121,000 less opioid prescriptions dispensed in 2018 alone.

Conclusions:

Occupational health policy interventions were associated with reductions in opioid prescribing within the DoD.
Factors Related to Physical and Mental Health in Workers With Different Categories of Employment
Authors: Park Jungsun , Kim Yangho
Published: May 2020

Introduction:

We examined a large representative sample of workers in South Korea to compare the subjective well-being and musculoskeletal symptoms of those with standard employment and those with non-standard employment (temporary, daily, and part-time work).

Methods:

This was a secondary analysis of data from the fifth Korean Working Condition Survey, conducted in 2017.

Results:

Female part-time workers who had temporary and daily jobs were more likely to have poor subjective well-being, whereas female regular workers with part-time jobs were less likely to have poor subjective well-being than regular workers with full-time jobs. Daily workers of both sex with full-time jobs were more likely to have musculoskeletal pain than regular workers.

Conclusion:

Our characterization of workers with precarious employment indicated that several modifiable factors affected the subjective well-being and musculoskeletal symptoms of these workers.
A National Survey of Health and Safety Knowledge and Beliefs Among Technical Vocational Faculty in Autobody Collision Repair Technology
Authors: Parker David L. , Bejan Anca , Marscin Melissa , Xi Min
Published: May 2020

Objectives:

Career technical education (CTE) programs prepare new generations of technicians in a variety of trades. Even though occupational safety and health (OSH) ought to be included as an essential part of CTE curricula it is frequently absent or inadequately taught.

Methods:

OSH knowledge and beliefs were assessed in a national sample of 125 secondary and post-secondary faculty in autobody collision repair technology.

Results:

Over 50% of faculty thought at least 75% of OSH knowledge was learned at school, and 9% felt that safety was primarily learned on the job. Knowledge scores ranged from 22% to 78%. Overall knowledge scores were significantly lower high school than post-secondary instructors (42% vs 50%, P ≤ 0.001) and in two categories: hazard recognition (44% vs 54%, P ≤ 0.05) and hazard control and shop equipment (30% vs 37%, P ≤ 0.05).

Conclusions:

There are substantial gaps in OSH knowledge among secondary and post-secondary CTE instructors. CTE programs should address these gaps by providing trade-specific safety and health education to their instructors upon hiring.
The effect of lung-conduction exercise in chronic obstructive pulmonary disease
Authors: Lee Su Won , Lyu Yee Ran , Park So Jung , Kwak Jin Young , Yang Won Kyung , Kim Seung Hyung , Kang Weechang , Son Ji Woong , Jung In Chul , Park Yang Chun
Published: May 2020

Background:

Chronic obstructive pulmonary disease (COPD) is an irreversible disease characterized by cough, sputum production, and dyspnea, and has a high prevalence and mortality. Pulmonary rehabilitation (PR) is a management that improves the quality of life for COPD patients; however, PR is not readily accessible. Therefore, we developed lung-conduction exercises (LCE) that can be performed without any limitations. LCE consists of breathing, stretching, and tapping to relieve dyspnea in COPD patients.

Methods/design:

This randomized, assessor-blind, multicenter trial aims to recruit 54 patients with moderate and severe COPD. Subjects will be randomly allocated to a control group (only medication), an LCE group (medication + LCE, 5 times a week), or a PR group (medication + PR, 5 times a week). The 6-minute walk distance, pulmonary function tests (forced expiratory volume at 1 second, forced vital capacity, and forced expiratory volume at 1 second/forced vital capacity), modified Borg scale, modified medical research council dyspnea scale, COPD assessment test, and St. George respiratory questionnaire will be measured before starting the trial and after the 4th and 8th weeks to determine motor performance, lung function, and dyspnea.

Conclusion:

We aim to demonstrate that LCE is effective in improving symptoms and psychosomatic stability in COPD patients. Therefore, this trial will play an important role in fortifying the foundation of clinical application.
Clinical significance of progranulin correlated with serum soluble Oxford 40 ligand in primary Sjögren's syndrome
Authors: Qi Xuan , Guo Huifang , Sun Chao , Tian Yu , Ding Meng , Yang Yushu , Jin Hongtao
Published: May 2020

The present study aimed to investigate the association between the expressions of serum progranulin (PGRN) and serum soluble Oxford 40 ligand (sOX40L) and determine their clinical significances in primary Sjögren's syndrome (pSS).

The present study included a total of 68 patients with pSS and 50 healthy controls. Demographic data and clinical basic information were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum levels of PGRN, sOX40L and interleukins. Spearman's correlation coefficient and Mann–Whitney U test were used to determine the correlation between PGRN, and sOX40L and the association between PGRN and sOX40L and disease activity and disease severity.

Serum interleukin (IL)-4, IL-6, IL-10, PGRN, and sOX40L levels were significantly higher in pSS patients as compared to the healthy controls. A positive correlation was observed between PGRN and sOX40L. Patients with elevated levels of PGRN or sOX40L exhibited higher disease activity compared to those with lower levels. Patients with III to IV stages of pSS or multiple system damage showed higher serum levels of PGRN and sOX40L.

Elevated serum PGRN, and sOX40L levels were relevant with disease activity and severity in patients with pSS.
A case report and literature review
Authors: Yan Zi , Gang Xiaokun , Xie Xiaona , Gao Ying , Li Zhuo , Wang Guixia
Published: May 2020

Rationale:

Autoimmune polyendocrine syndrome type 1 (APS-1), also referred as the autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy (APECED), is a rare autosomal inherited disease predominantly among Caucasians from Northern Europe. This syndrome is very rare in East Asian population.

Patients concerns:

Here, we describe a case of a 15-year-old Chinese boy admitted due to a 1-month history of intermittent fatigue, nausea, vomiting, and diarrhea. His symptom became worse accompanied with chest tightness 4 days before admission. On physical examination, his temperature was 38.5°C, blood pressure was 75/38 mm Hg, and pulse was 98/min. He was a thin boy with mild hyperpigmentation and xanthochromia.

Diagnosis:

After abdominal computed technology and laboratory tests, his diagnosis was APS-1 accompanied with adrenal crisis. Further investigation on whole-exome sequencing revealed a novel homozygous mutation c.47C>G (p.T16R) in exon 1 in the autoimmune regulator (AIRE) gene.

Interventions:

This patient underwent replacement therapy of glucocorticoids, corticosteroid, and levothyroxine, as well as calcium and calcitriol supplementation.

Outcomes:

He continues to do well 4 years after his hospitalization. During his last follow-up, he had serum thyroid-stimulating hormone level of 3.07 μIU/mL, free triiodothyronine level of 1.92 pg/mL, and free thyroxine level of 13.95 pg/mL. His serum cortisol and ACTH (8 a.m.) levels were 28.53 μg/dL and 69.48 pg/mL, respectively.

Lessons:

APS-1 is very rare in East Asians and the variable clinical presentations of the disease make the initial diagnosis especially difficult. Autoimmune thyroiditis, type 1 diabetes mellitus, and hepatitis were the three most frequent minor components of APS-1 in East Asian patients with age of onset in late teens and 20s. Sequence analysis of AIRE gene is necessary to verify its diagnostic efficacy in association with clinical findings.
Bilateral stellate ganglion block for migraine
Authors: Moon Suyoung , Lee Joonhee , Jeon Younghoon
Published: May 2020

Rationale:

Migraine is a recurrent, disabling neurovascular headache disorder. The patient's quality of life can be severely impaired by migraine attacks. Stellate ganglion block (SGB) can be used to relieve pain in the head, neck, and upper extremities. In the present cases, we performed SGB in 2 patients with migraine that responds poorly to drugs.

Patient concerns:

Patients 1 and 2 suffered from chronic, bilateral pulsating headache, accompanied by nausea and vomiting. Patient 1 presented with headache of 8 on the visual analog scale (VAS), and 37 on the migraine disability assessment (MIDAS). Patient 2 reported headache of 7 on the VAS, and 32 on the MIDAS.

Diagnosis:

The patients were diagnosed with migraine without aura based on the International Classification of Headache Disorders version 3.

Interventions:

Patient 1 was treated with bilateral SGB every week for a month and then every month for 3 months. Patient 2 received bilateral SGB every 2 weeks for a month and then every month for 3 months.

Outcomes:

Four months after SGB, patient 1 reported pain intensity of 4 on VAS and 6 on MIDAS and patient 2 rated pain intensity of 3 on VAS, and 6 on MIDAS, respectively.

Lessons:

The SGB can be an effective option to improve headache-related disability and relieve pain intensity in the patients with refractory migraine.
Gastric lymphoma complicated by phlegmonous gastritis and Guillain–Barré syndrome
Authors: Kuriyama Kodai , Koyama Yuki , Tsuto Kazuma , Tokuhira Natsuko , Nagata Hiroaki , Muramatsu Ayako , Oshiro Muneo , Hirakawa Yoshiko , Iwai Toshiki , Uchiyama Hitoji
Published: May 2020

Introduction:

Complications such as severe infection may occur during the chemotherapy of malignant lymphoma. Phlegmonous gastritis (PG) is a rare acute bacterial infection associated with high mortality, requiring early diagnosis, and prompt management. In addition, Guillain–Barré syndrome (GBS) occasionally requires early treatment and intensive care management due to the occurrence of severe neuropathy and respiratory failure.

Patient concerns:

A 70-year-old male was diagnosed with primary gastric diffuse large B-cell lymphoma (DLBCL) after the detection of several polypoid tumors with ulcers. The patient underwent chemotherapy for DLBCL and exhibited adverse effects (i.e., fever, vomiting, epigastric pain, and neutropenia). Computed tomography indicated widespread thickening in the gastric wall. Furthermore, approximately 2 weeks later, the patient presented with gradual symmetric lower extremity weakness and respiratory failure due to paralysis of the respiratory muscle.

Diagnoses:

DLBCL was diagnosed through a gastric tumor biopsy. On the basis of the computed tomography findings, a culture of gastric juice, nerve conduction studies, and clinical symptoms, this case of gastric lymphoma was complicated with PG and GBS.

Interventions:

The patient was treated with antimicrobial therapy and administration of granulocyte colony-stimulating factor for PG, and with intravenous immunoglobulin and intensive care management for GBS.

Outcomes:

Despite the aggressive progress of the condition, the patient improved without relapse of DLBCL.

Conclusion:

PG was regarded as a precedent infection of GBS. In this article, we present the first reported case of gastric lymphoma complicated with PG and GBS.
Clinical significance of the combined measurement of serum B7-H1 and interleukin-10 in colorectal cancer patients
Authors: Wang Peng , Li Chun , Ma Xuzhe , Gai Xiaodong
Published: May 2020

Colorectal cancer (CRC) patients have been shown to express a cytokine signature that is detectable in serum and contributes to cancer pathogenesis. The objective of this study was to evaluate the potential clinical significance of preoperative circulating cytokine levels in CRC patients.

The expression of serum B7-H1 and IL-10 was assessed by ELISA in 89 patients and 64 health volunteers. As a control marker, CEA serum levels were measured by electrochemical luminescence detection. The receiver operating characteristic (ROC) curve was used to analysis to demonstrate the potential diagnostic value of these biomarkers.

The expression of serum B7-H1 was significantly increased in CRC patients (P = .001) and associated with the progression of TNM stage and a positive association with serum IL-10 levels was also evident. Furthermore, serum B7-H1 and IL-10 expression was not influenced by age, gender, tumor location, or mass, whereas a relationship existed with tumor metastasis and TNM stage. The serum levels of B7-H1 and IL-10 on the 7th postoperative day were significantly decreased compared with that of preoperative serum levels (P = .001, P = .003 respectively). The area under the ROC curves (AUC) for B7-H1 and IL-10 were 0.7063 and 0.5706, respectively. The optimal sensitivity and specificity of B7-H1 for discriminating between colon cancer patients and healthy controls were 85.21% and 56.43%, respectively, using a cut-off value of 3.46 ng/mL. However, the combined ROC analysis using B7-H1 and IL-10 revealed an AUC of 0.8791, with a sensitivity of 90.63% and a specificity of 75.18%.

The outcomes of the present study demonstrate the clinical significance of serum B7-H1 and IL-10 concentrations. Combined detection of B7-H1 plus IL-10 showed significantly increased sensitivity and specificity for discriminating between colorectal cancer patients and healthy controls compared these markers detection individual. The measurement of B7-H1 or IL-10 in sera following surgery may provide an additional tool for assessing the curative effects of surgery in CRC patients.
Impact of neoadjuvant chemotherapy on survival prognosis and pathological downstaging in patients presenting with high-risk upper tract urothelial carcinoma
Authors: Li Kun , Xie Wenjie , Gao Liang , Huang Gaomin , Zhou Jiaming , Mei Baoyu , Chen Jie
Published: May 2020

Purpose:

Controversy remains with using neoadjuvant chemotherapy (NAC) in patients with upper tract urothelial carcinoma (UTUC). Thus, we conducted a systematic review and meta-analysis of the peer-reviewed literature to assess the role of NAC in high-risk UTUC patients.

Methods:

PubMed, EMBASE, and the Cochrane Library were the main sources of relevant studies. The search terms included: “Upper urothelial carcinoma”; “UTUC”; “Urinary tract cancer”; and “Transitional cell carcinoma” combined with “Neoadjuvant chemotherapy” and “adjuvant chemotherapy”. We studied the relationship of UTUC and NAC. Overall survival, recurrent-free survival, cancer-specific survival and pathological response rate in patients treated with/without NAC before radical surgery were evaluated.

Results:

Five trials were selected, and included 532 participants. Each of the included studies was retrospective. The combined analysis showed that when compared to controls, the pooled hazard ratios of overall survival, recurrence-free survival and cancer-specific survival were 0.47 (95% confidence interval [CI], 0.34–0.64; P < .00001); 0.50 (95% CI, 0.37–0.66; P < .00001); and 0.37 (95% CI, 0.25–0.54; P < .00001), respectively. It indicates the beneficial effects of NAC for the prognosis of survival in UTUC. Additionally, NAC was significantly associated with T-stage down-grading (T3/4 to ≤T2; OR=7.58 [4.66, 12.33]; P < .0001) and pathological lymph node status (N+ to N0; OR = 6.24 [2.57,15.15]; P < .00001).

Conclusions:

NAC treatment before radical nephron-ureterectomy significantly improves survival prognosis in patients with high-risk upper tract urothelial carcinoma. However, considerable prospective and randomized studies are needed to confirm this perspective.
Effects of Diabetic Ketoacidosis on Executive Function in Children With Type 1 Diabetes: Evidence From Wisconsin Card Sorting Test Performance
Authors: He Jing , Zhu Jiang , Xie Yuting , Du Hongyu , Li Shichen , Li Sihui , He Wenjuan , Li Xia , Zhou Zhiguang , Zhu Xiongzhao
Published: May 2020

Objective

Diabetic ketoacidosis (DKA) in patients with type 1 diabetes mellitus (T1DM) is known to affect memory function, but little is known about its impact on executive function. This study aimed to determine whether a history of DKA was associated with changes in executive function in children with T1DM.

Methods

The sample consisted of 99 patients with T1DM with histories of DKA, 82 patients with T1DM without DKA, and 100 healthy controls aged 7 to 18 years. Neuropsychological function and emotion assessments were performed in all participants. The Wisconsin Card Sorting Test (WCST) was used to assess executive function.

Results

Compared with healthy controls, the DKA group (but not the non-DKA group) had a significantly lower mean intelligence quotient (IQ; p = .006, Cohen d = 0.528) and a significantly higher rate of WCST perseverative errors (p = .006, Cohen d = 0.475). In the DKA group, the age at DKA onset was significantly associated with the IQ (p = .001) and the number of completed WCST categories (p = .046). Higher hemoglobin A1c levels were associated significantly with lower IQ (p < .001), increased rate of WCST perseverative errors (p = .015), and completion of fewer WCST categories (p = .027).

Conclusions

DKA has implications for executive function in children with T1DM. These findings emphasize the importance of DKA prevention in patients with known T1DM, especially younger children with newly diagnosed T1DM.
Intensive Care Unit-Acquired Weakness: Neuropathology
Authors: Swash Michael , de Carvalho Mamede
Published: May 2020

There is extensive evidence in the literature that both peripheral nerve fibers and muscle fibers are affected in the course of intensive care unit-acquired weakness. Peripheral nerve lesion is characterized by axonal degeneration, without inflammatory changes. Muscle fiber involvement is characterized by muscle fiber atrophy and loss of thick filaments, predominantly involving type 2 fibers, but myonecrosis (“acute necrotizing myopathy of intensive care”) has also been reported. Steroids can precipitate thick myofilament damage, probably to some extent also triggered by immobilization and neuromuscular junction blockade. Sepsis and a systemic inflammatory response cause muscle fiber injury because of the release of cytokines and chemokines that modulate enzymatic reactions related to proteolysis. Regarding axonal injury, hyperglycemia, hypoalbuminemia, inflammatory response, and hypoperfusion are accepted risk factors. Nerve and muscle biopsy are the best methods for detection of structural abnormalities, but these are invasive investigations; although not suitable for repeated studies, in selected cases, biopsies may have a role in diagnosis.
Left ventricular mass index and subendocardial myocardial function in children with chronic kidney disease, a transmural strain and three-dimensional echocardiographic study
Authors: El Tantawy Amira Esmat , Fadel Fatina , Abdelrahman Safaa M. , Nabhan Marwa , Ibrahim Reem , Fattouh Aya M. , Sayed Shaimaa , ElKhashab Khaled Mohamed , Afdal Peter , AbdelMassih Antoine Fakhry
Published: May 2020

Introduction

Left ventricular hypertrophy (LVH) is the commonest myocardial response to chronic kidney disease (CKD); this response has been regarded detrimental as it impairs the blood flow to the deepest layers of the myocardium causing progressive myocardial dysfunction. The aim of these series is to assess the determinants of LVH in CKD patients and its impact on subendocardial function in such patients.

Methods

This study has been conducted on 40 CKD patients (Group 1) and 40 age-matched controls, both groups were assessed by transmural echocardiography to determine the subepicardial and subendocardial global longitudinal strain (GLS) as an expression of the systolic function of each of those layers. LVH was assessed by calculation of left ventricle mass index (LVMI). Both groups underwent ambulatory blood pressure monitoring. Group 1 was assessed as regards lipid profile and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR).

Results

HOMA-IR proved to be a more important determinant of LV hypertrophy than SBP and DBP with a P of 0.01. Moreover subendocardial GLS was negatively correlated with LVMI with r = 0.69 and P < 0.01 denoting the negative effect. LVH plays on subendocardial function probably by impairing myocardial perfusion.

Conclusion

This study points toward the importance of insulin resistance in aggravation of myocardial remodeling in CKD patients; more studies are warranted to examine the role of insulin Sensitizers in reversing such remodeling and restoring subendocardial function in such important systemic disorder.
Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants
Authors: Fortuno Cristina , Lee Kristy , Olivier Magali , Pesaran Tina , Mai Phuong L. , de Andrade Kelvin C. , Attardi Laura D. , Crowley Stephanie , Evans D. Gareth , Feng Bing-Jian , Major Foreman Ann Katherine , Frone Megan N. , Huether Robert , James Paul A. , McGoldrick Kelly , Mester Jessica , Seifert Bryce A. , Slavin Thomas P. , Witkowski Leora , Zhang Liying , Plon Sharon E. , Spurdle Amanda B. , Savage Sharon A.
Published: May 2020

Germline pathogenic variants in TP53 are associated with Li-Fraumeni syndrome (LFS), an autosomal dominant cancer predisposition disorder associated with high risk of malignancy, including early onset breast cancers, sarcomas, adrenocortical carcinomas and brain tumors. Intense cancer surveillance for individuals with TP53 germline pathogenic variants has been shown to decrease mortality; therefore, accurate and consistent classification of variants across clinical and research laboratories is crucial to patient care. Here, we describe the work performed by the Clinical Genome Resource TP53 Variant Curation Expert Panel (ClinGen TP53 VCEP) focused on specifying the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification to the TP53 gene. Specifications were applied to twenty ACMG/AMP criteria while nine were deemed not applicable. The original strength level for ten criteria was also adjusted due to current evidence. Use of the TP53-specific guidelines and sharing of clinical data amongst experts and clinical laboratories led to a decrease in variants of uncertain significance from 28% to 12% in comparison with the original guidelines. The ClinGen TP53 VCEP recommends the use of these TP53-specific ACMG/AMP guidelines as the standard strategy for TP53 germline variant classification.
Genomic epidemiology ofCampylobacter jejuniassociated with asymptomatic pediatric infection in the Peruvian Amazon
Authors: Pascoe Ben , Schiaffino Francesca , Murray Susan , Méric Guillaume , Bayliss Sion C. , Hitchings Matthew D. , Mourkas Evangelos , Calland Jessica K. , Burga Rosa , Peñataro Yori Pablo , Jolley Keith A. , Cooper Kerry K. , Parker Craig T. , Olortegui Maribel Paredes , Kosek Margaret N. , Sheppard Samuel K.
Published: May 2020

Campylobacteris the leading bacterial cause of gastroenteritis worldwide and its incidence is especially high in low- and middle-income countries (LMIC). Disease epidemiology in LMICs is different compared to high income countries like the USA or in Europe. Children in LMICs commonly have repeated and chronic infections even in the absence of symptoms, which can lead to deficits in early childhood development. In this study, we sequenced and characterizedC. jejuni(n=62) from a longitudinal cohort study of children under the age of 5 with and without diarrheal symptoms, and contextualized them within a globalC. jejunigenome collection. Epidemiological differences in disease presentation were reflected in the genomes, specifically by the absence of some of the most common global disease-causing lineages. As in many other countries, poultry-associated strains were a major source of human infection but almost half of local disease cases (15 of 31) were attributable to genotypes that are rare outside of Peru. Asymptomatic infection was not limited to a single (or few) human adapted lineages but resulted from phylogenetically divergent strains suggesting an important role for host factors in the cryptic epidemiology of campylobacteriosis in LMICs.

Author summary

Campylobacteris the leading bacterial cause of gastroenteritis worldwide and despite high incidence in low- and middle-income countries (LMICs), where infection can be fatal, culture based isolation is rare and the genotypes responsible for disease have not broadly been identified. The epidemiology of disease is different to that in high income countries, where sporadic infection associated with contaminated food consumption typically leads to acute gastroenteritis. In some LMICs infection is endemic among children and common asymptomatic carriage is associated with malnutrition, attenuated growth in early childhood, and poor cognitive and physical development. Here, we sequenced the genomes of isolates sampled from children in the Peruvian Amazon to investigate genotypes associated with varying disease severity and the source of infection. Among the common globally circulating genotypes and local genotypes rarely seen before, no single lineage was responsible for symptomatic or asymptomatic infection – suggesting an important role for host factors. However, consistent with other countries, poultry-associated strains were a major source of infection. This genomic surveillance approach, that integrates microbial ecology with population based studies in humans and animals, has considerable potential for describing cryptic epidemiology in LMICs and will inform work to improve infant health worldwide.
Using the COVID-19 to influenza ratio to estimate the numbers of symptomatic COVID-19 cases in Wuhan prior to the lockdown
Authors: Du Zhanwei , Cowling Benjamin J. , Meyers Lauren Ancel
Published: May 2020

A recent study tested 45 throat swabs taken from adults over age 30 who sought outpatient care at one of two central Wuhan hospitals for influenza-like-illness between December 30, 2019 and January 19, 2020. Although none were confirmed COVID-19 cases, nine retrospectively tested positive for the virus. Using the fact that Wuhan has 393 other hospitals, we extrapolate the total number of undetected cases of symptomatic COVID-19 in adults during this period. we estimate that there were 5,558 [95% CI: 2,761-9,864] adults with symptomatic COVID-19 infections in Wuhan between December 30th and January 19th, 2020.
A first study on the impact of containment measure on COVID-19 spread in Morocco
Authors: Hammoumi Aayah , Qesmi Redouane
Published: May 2020

Background

Since the appearance of the first case of COVID-19 in Morocco, the cumulative number of reported infectious cases continues to increase and, consequently, the government imposed the containment measure within the country. Our aim is to predict the impact of the compulsory containment on COVID-19 spread. Earlier knowledge of the epidemic characteristics of COVID-19 transmission related to Morocco will be of great interest to establish an optimal plan-of-action to control the epidemic.

Method

Using a Susceptible-Asymptomatic-Infectious model and the data of reported cumulative confirmed cases in Morocco from March 2nd to April 9, 2020, we determined the basic and control reproduction numbers and we estimated the model parameter values. Furthermore, simulations of different scenarios of containment are performed.

Results

Epidemic characteristics are predicted according to different rates of containment. The basic reproduction number is estimated to be 2.9949, with CI(2.6729–3.1485). Furthermore, a threshold value of containment rate, below which the epidemic duration is postponed, is determined.

Conclusion

Our findings show that the basic reproduction number reflects a high speed of spread of the epidemic. Furthermore, the compulsory containment can be efficient if more than 73% of population are confined. However, even with 90% of containment, the end-time is estimated to happen on July 4th which can be harmful and lead to consequent social-economic damages. Thus, containment need to be accompanied by other measures such as mass testing to reduce the size of asymptomatic population. Indeed, our sensitivity analysis investigation shows that the COVID-19 dynamics depends strongly on the asymptomatic duration as well as the contact and containment rates. Our results can help the Moroccan government to anticipate the spread of COVID-19 and avoid human loses and consequent social-economic damages as well.
Clinical-grade whole genome sequencing of colorectal cancer and 3’ transcriptome analysis demonstrate targetable alterations in the majority of patients
Authors: Stodolna Agata , He Miao , Vasipalli Mahesh , Kingsbury Zoya , Becq Jennifer , Stockton Joanne D , Dilworth Mark P , James Jonathan , Sillo Toju , Blakeway Daniel , Ward Stephen T , Ismail Tariq , Ross Mark T. , Beggs Andrew D.
Published: May 2020

Introduction

Clinical grade whole genome sequencing (cWGS) has the potential to become standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3’ transcriptome analysis would give new insights into colorectal cancer.

Methods

Patients underwent PCR-free whole genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into mutational signatures and tumour biology were gained by the use of 3’ RNAseq.

Results

Fifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 20% of patients had a tumour mutational burden of >10 mutations/Mb of DNA, suggesting suitability for immunotherapy.

Conclusions

Clinical whole genome sequencing offers a potential avenue for identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.
A Fundamental Inconsistency in the SIR Model Structure and Proposed Remedies
Authors: Nikolaou Michael
Published: May 2020

The susceptible-infectious-removed (SIR) compartmental model structure and its variants are a fundamental modeling tool in epidemiology. As typically used, however, this tool may introduce an inconsistency by assuming that the rate of depletion of a compartment is proportional to the content of that compartment. As mentioned in the seminal SIR work of Kermack and McKendrick, this is an assumption of mathematical convenience rather than realism. As such, it leads to underprediction of the infectious compartment peaks by a factor of about two, a problem of particular importance when dealing with availability of resources during an epidemic. To remedy this problem, we develop the dSIR model structure, comprising a single delay differential equation and associated delay algebraic equations. We show that SIR and dSIR fully agree in assessing stability and long-term values of a population through an epidemic, but differ considerably in the exponential rates of ascent and descent as well as peak values during the epidemic. The novel Padé-SIR structure is also introduced as a approximation of dSIR by ordinary differential equations. We rigorously analyze the properties of these models and present a number of illustrative simulations, particularly in view of the recent coronavirus epidemic. Suggestions for further study are made.
Pooled testing with replication: a mass testing strategy for the COVID-19 pandemics
Authors: Žilinskas Julius , Lančinskas Algirdas , Guarracino Mario R.
Published: May 2020

In absence of a vaccine or antiviral drugs for the COVID-19 pandemic, it becomes urgent to test for positiveness to the virus as many people as possible, in order to detect early outbreaks of the infection. Present testing solutions are based on the extraction of RNA from patients using oropharyngeal (OP) and nasopharyngeal (NP) swabs, and then testing with real-time PCR for the presence of specific RNA filaments identifying the virus. This approach is limited by the availability of reactants, trained technicians and laboratories. To speed up the testing procedures, some attempts have been done on group testing, which means that the swabs of multiple patients are grouped together and tested. Here we propose to use this technique in conjunction with a combinatorial replication scheme in which each patient is allocated in two or more groups to reduce total numbers of tests and to allow testing of even larger numbers of people. Under mild assumptions, a 13× average reduction of tests can be achieved.
Causal effects of senescence through intrinsic epigenetic age acceleration on age-related diseases: a Mendelian randomization study
Authors: Gatto F. , Ueda P.
Published: May 2020

Older age is associated with many diseases. However, it is unclear whether the biological mechanisms underpinning senescense (biological ageing) is a cause of age-related diseases (ARDs). In this Mendelian randomization study, we examined the causal effects of intrinsic epigenetic age acceleration (IEAA) - a process assumed downstream of senescence - on the occurrence of ARDs. In a metanalysis of 18 genome-wide association studies (GWAS) spanning 12 ARDs in ~27 million people of European ancestry (median per GWAS: 17’008 cases vs. 40’940 controls), IEAA-associated SNPs did not significantly increase the risk of ARDs as a group (odds-ratio (OR) = 0.99) nor of any individual ARD (OR range: 0.87-1.04). However, one SNP, rs2736099 on TERT, was significantly associated with 8 of 10 ARDs with increased risk for lung and ovarian cancer, atrial fibrillation, and benign prostatic hyperplasia and lower risk for Alzheimer’s disease, rheumatoid arthritis, cardiovascular artery disease and breast cancer. No associations between rs2736099 and known ARD risk factors were found strengthening the causal role of rs2736099-associated senescence. While IEAA was not found as a unifying cause of ARDs, senescence seems to cause some ARDs while preventing others through a mechanism only partially affecting IEAA and associated with rs2736099.
Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study
Authors: Mallat Jihad , Hamed Fadi , Balkis Maher , Mohamed Mohamed A. , Mooty Mohamad , Malik Asim , Nusair Ahmad , Bonilla Maria-Fernanda
Published: May 2020

Background

There is conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients

Objective

To assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance

Design

Retrospective observational study

Setting

Cleveland Clinic Abu Dhabi

Participants

Hospitalized adult patients with confirmed SARS-CoV-2 infection

Intervention

None

Measurements

The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by two negative results using RT-PCR assay with samples obtained 24 hours apart

Results

34 confirmed COVID-19 patients were included. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ compared to those who did not receive HCQ (17 [13–21] vs. 10 [4–13] days, p=0.023). HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, pneumonia or oxygen therapy) in multivariable linear regression analysis. On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared to 90.9% (10/11) patients who did not receive HCQ (p=0.016).

Limitations

Small sample size and retrospective design with a potential risk of selection bias

Conclusion

HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.
Notch and TLR signaling coordinate monocyte cell fate and inflammation
Authors: Gamrekelashvili Jaba , Kapanadze Tamar , Sablotny Stefan , Ratiu Corina , Dastagir Khaled , Lochner Matthias , Karbach Susanne , Wenzel Philip , Sitnow Andre , Fleig Susanne , Sparwasser Tim , Kalinke Ulrich , Holzmann Bernhard , Haller Hermann , Limbourg Florian P.
Published: May 2020

Conventional Ly6Chimonocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chimonocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clopatrolling monocyte development from Ly6Chimonocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clomonocyte development. At the same time, TLR7 stimulation in the absence of functional Notch2 signaling promotes resident tissue macrophage gene expression signatures in monocytes and ectopic differentiation of Ly6Chimonocytes into macrophages and dendritic cells, which appear in the blood stream and infiltrate the spleen and major blood vessels, resulting in unrestrained systemic inflammation. Thus, Notch2 is a master regulator of Ly6Chimonocyte cell fate and inflammation in response to TLR signaling.
FACT- Frankfurt adjusted COVID-19 testing- a novel method enables high-throughput SARS-CoV-2 screening without loss of sensitivity
Authors: Schmidt Michael , Hoehl Sebastian , Berger Annemarie , Zeichhardt Heinz , Hourfar Kai , Ciesek Sandra , Seifried Erhard
Published: May 2020

Background

In the pandemic, testing for SARS-CoV-2 by RT-PCR in one of the pillars on which countermeasures are based. Factors limiting the output of laboratories interfere with the effectiveness of public health measures. Conserving reagents by pooling samples in low-probability settings is proposed, but may cause dilution and loss of sensitivity.

Methods

We tested an alternate approach (FACT) by simultaneously incubating multiple respiratory swabs in a single tube. This protocol was evaluated by serial incubation of a respiratory swab in up to 10 tubes. The analytics validity of this concept was demonstrated in a five-sample mini pool set-up. It was consequently applied in the testing of 50 symptomatic patients (five-sample pools) as well as 100 asymptomatic residents of a nursing home (ten-sample pools).

Results

Serial incubation of a respiratory swab in up to 10 tubes did not lead to a significant decline in viral concentration. The novel FACT-protocol did not cause a false negative result in a five-sample mini-pool setup, with non-significantly differing Ct values between single sample and mini-pool NAT. In two routine applications, all mini pools containing positive patient samples were correctly identified.

Conclusions

Our proposed FACT-protocol did not cause a significant loss in analytic or diagnostic sensitivity compared to single sample testing in multiple setups. It reduced the amount of reagents needed by up to 40%, and also reduced hands-on time. This method could enhance testing efficiency, especially in groups with a low pretest-probability, such as systemically relevant professional groups.