bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary carbohydrates and weight loss maintenance
Authors: van Baak Marleen A.
Published: April 2021

Purpose of review

Aim of the present review is to provide an overview of the effect of manipulating dietary carbohydrates (content, type) after a period of weight loss on weight loss maintenance and its potential underlying mechanisms.

Recent findings

Few recent studies directly tested whether lower carbohydrate/glycaemic load or higher fibre diets help to limit weight regain after weight loss and they did not provide evidence supporting a role of a reduction of the carbohydrate or an increase of the fibre content of the diet in the prevention of weight regain after weight loss. Some evidence is emerging that personal characteristics (gut microbiota, glycaemia) may interact with diet composition. but randomized clinical trials are needed to substantiate these claims.

There is currently no convincing evidence that lowering dietary carbohydrates has a clinically relevant effect on weight regain after weight loss, unless there is an increase in protein intake at the same time. Further randomized trials are needed to investigate potential interactions with personal characteristics while improving strategies for long-term adherence.
Recent advances and current controversies in genetic testing for personalized nutrition
Authors: Garcia-Bailo Bibiana , El-Sohemy Ahmed
Published: April 2021

Purpose of review

Considerable interest in personalized nutrition exists among the general public, policymakers, healthcare organizations and the private sector, but there is also skepticism of its utility. The present review aims to provide a summary of current controversies in the field of nutrigenomics, and to highlight recent research on the potential impact of implementing genetic testing for personalized nutrition in practice.

Recent findings

Numerous companies already offer genetic testing for personalized nutrition based on research developments in nutritional genomics. However, controversy exists over whethexr genetics contributes to interindividual responses to diet; the utility of single genetic variants versus genetic risk scores; the ability of DNA-based nutritional advice to elicit positive behavior change and health effects; and whether genetic information makes a difference on the type of dietary advice provided. Potential factors contributing to the discrepant viewpoints are discussed.

Despite the existing controversies, a solid body of evidence demonstrates that genetic testing for personalized nutrition is a powerful tool to guide dietary recommendations to improve health and performance, and to elicit positive behavior change.
COVID-19: reflections on providing dysphagia care in a Boston hospital
Authors: Goldsmith Tessa
Published: April 2021

Purpose of review

Coronavirus Disease-19, (COVID-19) has challenged the customary practice of speech language pathologists (SLPs) in the acute care hospital arena, particularly in patients with swallowing disorders.

Recent findings

In this article, we present themes that emerged from qualitative interviews in which 15 SLPs in a tertiary academic medical center in Boston share their clinical experience caring for over 500 patients with COVID-19: triumphs, concerns, and fears.

The broad themes addressed include adapting to practice laced with fear and uncertainty about safety for themselves and their decision making, coming to terms with disparate and unpredictable clinical presentation, teamwork and collaboration and relationships with their patients despite physical and language barriers.
Henoch-Schönlein Purpura With Scrotal Involvement: A Case Report and Literature Review
Authors: Ma Yue , Zhang Shanyun , Chen Jiye , Kong Han , Diao Juanjuan
Published: April 2021

Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels, leading to arthritis, abdominal pain, and renal involvement. However, scrotal involvement is a rare complication of HSP and scrotal pain. Swelling is the most frequent clinical presentation and can be easily confused with testicular torsion. If not treated in time, the scrotal inflammation will result in irreversible testicular necrosis. We report a 6-year-old male with HSP and scrotal involvement, characterized by swelling and pain on the left side of the scrotum, rashes on both lower extremities, and epididymitis. He was treated with conservative care, corticosteroids, and antibiotic therapy. We were able to avoid surgical intervention. On the 10 days of treatment, he recovered sufficiently well and was discharged. We have reviewed the literature related to HSP with scrotal involvement, identified 21 cases, and revealed that steroid therapy and/or antibiotics are the first-line of therapy in children with scrotal involvement. Vasculitis in the scrotum may predispose to testicular torsion, which is a complication that should not be overlooked. Clinicians should be aware of the atypical types of HSP. Timely diagnosis and appropriate treatment are essential for achieving the best results.
Predictors of Participation in Clinical Research
Authors: Scanlon Jennifer K. , Wofford Linda , Fair Alecia , Philippi David
Published: April 2021

Background

Despite numerous efforts to create more equitable healthcare systems, minority populations face long-standing health disparities compared to White populations. Healthcare research is the necessary foundation for creating equitable health systems and providing patient-centered care. Significant challenges exist, however, with recruiting and engaging underrepresented populations in clinical research.

Objectives

The purpose of this analysis was to determine how research participants' race, trust, and level of education influence participation barriers in clinical research.

Methods

The study used secondary, cross-sectional survey data that were collected between 2014 and 2016 through the former Mid-South Clinical Data Research Network, currently known as the Stakeholders, Technology, and Research Clinical Research Network. Descriptive statistics and Spearman rank correlations were performed between level of education, level of trust, and each attitude statement for each racial category.

Results

A total of 2,190 survey responses were used in the data analysis. The mean age of respondents was 52 years, with majority being women, White, insured, and working full time. Overall, the respondents had favorable attitudes toward research participation. Trust was correlated with agreement in many attitude statements for both White and African American respondents, whereas correlations with education level were more variable depending on racial grouping. Trust level was negatively associated with agreement toward the statement “researchers do not care about me” in White and Native American respondents.

Discussion

The results support the importance of trust to research participation. Generally, education level was not strongly predictive of research participation, although prediction was influenced by race and attitude.
The Nasoalveolar Molding Cleft Protocol: Long-Term Treatment Outcomes from Birth to Facial Maturity
Authors: Yarholar Lauren M. , Shen Chen , Wangsrimongkol Buddhathida , Cutting Court B. , Grayson Barry H. , Staffenberg David A. , Shetye Pradip R. , Flores Roberto L.
Published: April 2021

Background:

The authors present outcomes analysis of the nasoalveolar molding treatment protocol in patients with a cleft followed from birth to facial maturity.

Methods:

A single-institution retrospective review was conducted of cleft patients who underwent nasoalveolar molding between 1990 and 2000. Collected data included surgical and orthodontic outcomes and incidence of gingivoperiosteoplasty, alveolar bone grafting, surgery for velopharyngeal insufficiency, palatal fistula repair, orthognathic surgery, nose and/or lip revision, and facial growth.

Results:

One hundred seven patients met inclusion criteria (69 with unilateral and 38 with bilateral cleft lip and palate). Eighty-five percent (91 of 107) underwent gingivoperiosteoplasty (unilateral: 78 percent, 54 of 69; bilateral: 97 percent, 37 of 38). Of those patients, 57 percent (52 of 91) did not require alveolar bone grafting (unilateral: 59 percent, 32 of 54; bilateral: 54 percent, 20 of 37). Twelve percent (13 of 107) of all study patients underwent revision surgery to the lip and/or nose before facial maturity (unilateral: 9 percent, six of 69; bilateral: 18 percent, seven of 38). Nineteen percent (20 of 107) did not require a revision surgery, alveolar bone grafting, or orthognathic surgery (unilateral: 20 percent, 14 of 69; bilateral: 16 percent, six of 38). Cephalometric analysis was performed on all patients with unilateral cleft lip and palate. No significant statistical difference was found in maxillary position or facial proportion. Average age at last follow-up was 20 years (range, 15 years 4 months to 26 years 10 months).

Conclusions:

Nasoalveolar molding demonstrates a low rate of soft-tissue revision and alveolar bone grafting, and a low number of total operations per patient from birth to facial maturity. Facial growth analysis at facial maturity in patients who underwent gingivoperiosteoplasty and nasoalveolar molding suggests that this proposal may not hinder midface growth.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Five Reliable Nerve Transfers for the Treatment of Isolated Upper Extremity Nerve Injuries
Authors: Peters Blair R. , Van Handel Amelia C. , Russo Stephanie A. , Moore Amy M.
Published: April 2021

Learning Objectives:

After studying this article and accompanying videos, the participant should be able to: 1. Understand and apply the principles of nerve transfer surgery for nerve injuries. 2. Discuss important considerations when performing nerve transfers, such as aspects of surgical technique and perioperative decision-making. 3. Understand indications for end-to-end versus supercharged reverse end-to-side nerve transfers. 4. Understand an algorithm for treating nerve injuries to include the indications and surgical techniques of five nerve transfers commonly performed for the treatment of isolated upper extremity nerve injuries. 5. Understand the outcomes and postoperative management of the discussed nerve transfers.

Nerve transfers are gaining wide acceptance because of their superior results in the management of many nerve injuries of the upper extremity. This article presents five nerve transfers for the treatment of isolated nerve injuries in the authors’ upper extremity nerve practice that offer reliable results. Indications, surgical techniques, outcomes, and postoperative management are reviewed. To maximize functional outcomes in patients with nerve injuries, the treatment should be individualized to the patient, and the principles for nerve transfers as described herein should be considered.
Advanced Practice Providers in Plastic Surgery
Authors: Seyidova Nargiz , Chen Austin D. , Lee Joël , Alnaeem Hassan , Grover Ritwik , Lin Samuel J.
Published: April 2021

Background:

The aims of this article are to examine the scope of practice differences between physician assistant and nurse practitioner providers, to identify financial cost and benefits, and to posit the impact of physician extenders on plastic surgery practices.

Methods:

A review of the literature was performed using the PubMed database. Key words included “plastic surgery AND physician extender AND cost,” “plastic surgery AND physician assistant AND cost,” and “plastic surgery AND nurse practitioner AND cost.” Secondarily, a search was performed for plastic surgery–related specialties of maxillofacial surgery, orthopedic surgery, and otolaryngology. Inclusion criteria consisted of any study design measuring the financial benefits associated with integrating physician extenders.

Results:

The PubMed search yielded 91 articles. Eight articles were ultimately included, of which four (plastic, maxillofacial, and orthopedic) discussed the impact of physician assistants and four (orthopedic and otolaryngology) discussed the impact of nurse practitioners. All eight studies demonstrated that integration of physician assistants and nurse practitioners into practices was associated with a net financial gain even after taking into account their overall costs, along with other outcomes such as productivity or time involvement.

Conclusions:

As the number of physician extenders continues to grow, especially in subspecialties, plastic surgeons should be aware of their roles and the potentially positive impact of these providers, their respective training, and their quantifiable financial impact toward a plastic surgery practice. Both physician assistants and nurse practitioners appear to have a positive effect on costs in plastic surgery and plastic surgery–related practices.
Gynecomastia Treatment through Open Resection and Pectoral High-Definition Liposculpture
Authors: Hoyos Alfredo E. , Perez Mauricio E. , Domínguez-Millán Rodrigo
Published: April 2021

Background:

Male chest definition surgery and patients complaining of breast tissue overgrowth have been increasing in recent decades. After the authors’ first report of pectoral etching in 2012, patients and surgeons became more aware about gynecomastia resection when performing pectoral enhancement. The authors present their experience with pectoral high-definition liposculpture in addition to inverted-omega incision resection for gynecomastia.

Methods:

The authors reviewed their records on pectoral high-definition lipo sculpture between January of 2005 and October of 2019 in four surgical centers in Colombia. Inclusion criteria were as follows: men diagnosed with gynecomastia and body mass index less than or equal to 32 kg/m2, adequate skin elasticity, and general good health. Photographs were taken preoperatively and 1, 3, 6, and 12 months postoperatively. Follow-up ranged from 2 months to 3 years.

Results:

Gynecomastia resection plus high-definition liposculpture was successfully performed in 436 consecutive men (open inverted-omega incision resection, n = 132; liposuction, n = 304). Ages ranged from 18 to 66 years. Fat grafting volume ranged from 50 to 300 cc in each pectoral muscle. Minor complications (3.2 percent) included prolonged swelling, bruising, asymmetries, and residual gynecomastia. Major complications (1.6 percent) included unilateral hematoma and localized infection. No necrosis, systemic infection, or muscle paralysis was reported. A nonstandardized survey showed a very high satisfaction index.

Conclusion:

Gynecomastia treatment combining high-definition liposculpture to male breast tissue resection through a new, almost invisible incision allowed us to achieve an athletic and natural appearance of the male pectoral area with a very low rate of complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Analysis of the Effects of Coordination Program Viva 2 Parkinson (CoVi2) on Dynamic Balance, Muscle Parameters, and Symptomatology in Older Adults Diagnosed With Advanced Stages of Parkinson's Disease
Authors: Pereira-Pedro Karina Pitombeira , Mollinedo-Cardalda Irimia , Carral José Maria Cancela
Published: April 2021

There is evidence to suggest that assisted cycling can effectively improve the motor function of patients with Parkinson's disease (PD) and an assisted cycling intervention is more beneficial for those with more advanced PD. Therefore, the aim of this study was to investigate the influence of an intervention with a coordination program at MOTOmed Viva 2 Parkinson on dynamic balance, muscle parameters, and symptoms in elderly people diagnosed with advanced stages of PD. We studied 4 elderly people with PD in advanced stages. We evaluated PD symptomatology using the adapted Spanish version of the MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease Rating Scale); dynamic balance was evaluated by means of the Timed Up and Go (TUG) and the MOTOmed Viva 2 Parkinson system stores data about muscle tone, symmetry, coordination, and spasms, in each of the sessions undertaken. We found that a 21-minute coordination training in 13 sessions with the MOTOmed device demonstrates positive effects on muscle tone, spasms, coordination, symmetry, and balance in older adults diagnosed with advanced stages of PD.
Understanding the Impact of Pneumonia and Other Complications in Elderly Liver Transplant Recipients: An Analysis of NSQIP Transplant
Authors: Schnickel Gabriel T. , Greenstein Stuart , Berumen Jennifer A. , Elias Nahel , Sudan Debra L , Conzen Kendra D. , Mekeel Kristin L. , Foley David P. , Hirose Ryutaro , Parekh Justin R.
Published: April 2021

Background.

Despite an increasing demand for liver transplantation in older patients, our understanding of posttransplant outcomes in older recipients is limited to basic recipient and graft survival. Using National Surgical Quality Improvement Program Transplant, we tracked early outcomes after liver transplantation for patients >65.

Methods.

We conducted a retrospective analysis of patients in National Surgical Quality Improvement Program Transplant between March 1, 2017 and March 31, 2019. Recipients were followed for 1 y after transplant with follow-up at 30, 90, and 365 d. Data were prospectively gathered using standard definitions across all sites.

Results.

One thousand seven hundred thirty-one adult liver transplants were enrolled; 387 (22.4%) were >65 y old. The majority of older recipients were transplanted for hepatocellular carcinoma. The older cohort had a lower lab Model for End-Stage Liver Disease and was less likely to be hospitalized at time of transplant. Overall, older recipients had higher rates of pneumonia but no difference in intensive care unit length of stay (LOS), total LOS, surgical site infection, or 30-d readmission. Subgroup analysis of patients with poor functional status revealed a significant difference in intensive care unit and total LOS. Pneumonia was even more common in older patients and had a significant impact on overall survival.

Conclusions.

By targeting patients with hepatocellular carcinoma and lower Model for End-Stage Liver Diseases, transplant centers can achieve nearly equivalent outcomes in older recipients. However, older recipients with poor functional status require greater resources and are more likely to develop pneumonia. Pneumonia was strongly associated with posttransplant survival and represents an opportunity for improvement. By truly understanding the outcomes of elderly and frail recipients, transplant centers can improve outcomes for these higher-risk recipients.
Post-vaccination SARS-CoV-2 infections and incidence of the B.1.427/B.1.429 variant among healthcare personnel at a northern California academic medical center
Authors: Jacobson Karen B. , Pinsky Benjamin A. , Rath Maria E. Montez , Wang Hannah , Miller Jacob A. , Skhiri Mehdi , Shepard John , Mathew Roshni , Lee Grace , Bohman Bryan , Parsonnet Julie , Holubar Marisa
Published: April 2021

Background

Distribution of mRNA-based SARS-CoV-2 vaccines to healthcare personnel (HCP) in the United States began in December 2020, with efficacy>90%. However, breakthrough infections in fully vaccinated individuals have been reported. Meanwhile, multiple SARS-CoV-2 variants of concern have emerged worldwide, including the B.1.427/B.1.429 variant first described in California. Little is known about the real-world effectiveness of the mRNA-based SARS-CoV-2 vaccines against novel variants including B.1.427/B.1.429.

Methods

In this quality improvement project, post-vaccine SARS-CoV-2 cases (PVSCs) were defined as individuals with positive SARS-CoV-2 nucleic acid amplification test (NAAT) after receiving at least one dose of a SARS-CoV-2 vaccine. Chart extraction of demographic and clinical information was performed, and available specimens meeting cycle threshold value criteria were tested for L452R, N501Y and E484K mutations by RT-PCR.

Results

From December 2020 to March 2021, 189 PVSCs were identified out of 22,729 healthcare personnel who received at least one dose of an mRNA-based SARS-CoV-2 vaccine. Of these, 114 (60.3%) occurred within 14 days of first vaccine dose (early post-vaccination), 49 (25.9%) within 14 days of the second vaccine dose (partially vaccinated), and 26 (13.8%)>14 days after the second dose (fully vaccinated). Of 115 samples available for mutation testing, 42 were positive for L452R alone, presumptive of B.1.427/B.1.429; three had N501Y mutation alone and none were found with E484K mutation. Though on univariate analysis partially- and fully-vaccinated PVSCs were more likely than early post-vaccination PVSCs to be infected with presumptive B.1.427/B.1.429, when adjusted for community prevalence of B.1.427/B.1.429 at the time of infection, partially- and fully-vaccinated PVSC did not have statistically significantly elevated risk ratios for infection with this variant (RR 1.40, 95% CI 0.81-2.43 and RR 1.13, 95% CI 0.59-2.16, respectively).

Conclusions

The great majority of PVSCs occurred prior to the expected onset of full, vaccine-derived immunity. Although the B.1.427/B.1.429 variant did not represent a significantly higher proportion of PVSCs than expected, numbers were small and there was a trend towards higher representation in the partially- and fully-vaccinated subset. Continued infection control measures in the workplace and in the community including social distancing and masking, particularly in the early days post-vaccination, as well as continued variant surveillance in PVSCs, is imperative in order to anticipate and control future surges of infection.
Preliminary study on the pathogenesis of anal fistula
Authors: Zhu Jingyi , Wang Qingming , Mei Zubing
Published: April 2021

BACKGROUND

Anal gland infection is one of the main pathogenic factors of anal fistula. The anal gland is mainly consist of columnar epithelial cells and goblet cells. Goblet cells could secrete mucins which maintain the surface mucous gel layer of intestine to prevent columnar epithelial cells from the direct acting of bacteria. The absence or diminished secretion of goblet cells could lead to the exposure of columnar epithelial cells to bacteria. In recent years, studies have found that most of the microorganisms in perianal abscess and anal fistula are intestinal bacteria. So, it can be considered that the occurrence and development of anal fistula is closely related to gut microbiota. However, the molecular mechanism of gut microbiota acting on the epithelial cells of anal gland leading to the occurrence and development of anal fistula has not been explored.

METHODS

Anal fistula tissues were collected from 30 patients, and HE staining was employed to observe pathological changes of anal gland. Stool specimens were collected from normal group (14 normal subjects), preoperative group (21 subjects before surgery) and postoperative group (16 subjects after surgery). High-throughput 16S rRNA gene sequencing was performed to explore differences among different groups.

RESULTS

It was found by HE staining that normal anal gland is composed of a large number of columnar epithelial cells as well as goblet cells, while the anal gland of patients with anal fistula is seriously lack of goblet cells. In the normal ones, a large number of vacuoles formed by the dye dissolution of mucin particles can be seen at the top of the goblet cells, and a large amount of mucin secretion can be seen in the center of the anal gland. The results of high-throughput 16S rRNA gene sequencing showed that there were significant statistical differences in species richness, species evenness and species composition between the preoperation group and the normal group (P1 =0.00004), and between the preoperative group and the postoperative group (P2 =0.00003). It also showed that PWY-6471 metabolic pathway was the most significant difference between the preoperative group and the postoperative group (P=0.0033).

CONCLUSIONS

The occurrence of anal fistula may be related to the abnormal permeability of mucus layer and the change of intestinal flora composition. The absence or diminished secretion of goblet cells may cause exception of the permeability of mucus layer which makes the columnar epithelial cells of anal gland exposed to the direct contact of peptidoglycan. The metabolite of pathogenic microorganisms could activate the signal pathway (i.g. NLR/NF-κB) which leading to the overexpression of inflammatory factors and cause anal fistula.
Associations of genetic scores for birth weight with newborn size and later Anthropometric traits and cardiometabolic risk markers in South Asians
Authors: Nongmaithem Suraj S , Beaumont Robin N , Dedaniya Akshay , Wood Andrew R , Ogunkolade Babatunji-William , Hassan Zahid , Krishnaveni Ghattu V , Kumaran Kalyanaraman , Potdar Ramesh D , Sahariah Sirajul A , Krishna Murali , Di Gravio Chiara , Mali Inder D , Sankareswaran Alagu , Hussain Akhtar , Bhowmik Biswajit W , Khan Abdul Kalam A , Knight Bridget A , Frayling Timothy M , Finer Sarah , Fall Caroline HD , Yajnik Chittaranjan S , Freathy Rachel M , Hitman Graham A , Chandak Giriraj R
Published: April 2021

We recently reported genetic variants associated with birth weight and their effect on future cardiometabolic risk in Europeans. Despite a higher burden of low birth weight and cardiometabolic disorders, such studies are lacking in South Asians. We generated fetal and maternal genetic scores (fGS and mGS) from 196 birth weight-associated variants identified in Europeans and conducted association analysis with various birth measures and serially measured anthropometric and cardiometabolic traits from seven Indian and Bangladeshi cohorts. Although fGS and mGS were comparable to Europeans, birth weight was substantially smaller suggesting strong environmental constraints on fetal growth in South Asians. Birth weight increased by 50.7g and 33.6g per standard deviation fGS (P=9.1×10−11) and mGS (P=0.003) in South Asians. The fGS was further associated with childhood body size and head circumference, fasting glucose, and triglycerides in adults (P<0.01). Our study supports a common genetic mechanism partly explaining associations between early development and later cardiometabolic health in different populations, despite phenotypic and environmental differences.
Towards fast, routine blood sample quality evaluation by Probe Electrospray Ionization (PESI) metabolomics
Authors: Bordag Natalie , Zügner Elmar , López-García Pablo , Kofler Selina , Tomberger Martina , Al-Baghdadi Abdullah , Schweiger Jessica , Erdem Yasemin , Magnes Christoph , Hidekazu Saiki , Wadsak Wolfgang , Erxleben Björn-Thoralf , Prietl Barbara
Published: April 2021

Abstract

PESI-MS enables with its greatly simplified handling and fast result delivery the application field for high-throughput use in routine settings. In health care and research, pre-analytical errors often remain undetected and disrupt diagnosis, treatment, clinical studies and biomarker validations incurring high costs. This proof-of-principle study investigates the suitability of PESI-MS for robust, routine sample quality evaluation.

One of the most common pre-analytical quality issues in blood sampling are prolonged transportations times from bedside to laboratory promptly changing the metabolome. Here, human blood (n=50) was processed immediately or with a time delay of 3 h. The developed sample preparation method delivers ready-to-measure extracts in <8 min. PESI-MS spectra were measured in both ionization modes in 2 min from as little as 2 µl plasma allowing 3 replicate measurements. The mass spectra contained 1200 stable features covering a broad chemical space covering major metabolic classes (e.g. fatty acids, lysolipids, lipids). The time delay of 3 h was predictable by using 18 features with AUC > 0.95 with various machine learning and was robust against loss of single features.

Our results serve as first proof of principle for the unique advantages of PESI-MS in sample quality assessments. The results pave the way towards a fully automated, cost-efficient, user-friendly, robust and fast quality assessment of human blood samples from minimal sample amounts.

Graphical abstract
Tracking white and grey matter degeneration along the spinal cord axis in degenerative cervical myelopathy
Authors: Vallotton Kevin , David Gergely , Hupp Markus , Pfender Nikolai , Cohen-Adad Julien , Fehlings Michael , Samson Rebecca S. , Wheeler-Kingshott Claudia A. M. Gandini , Curt Armin , Freund Patrick , Seif Maryam
Published: April 2021

Objective

To determine tissue-specific neurodegeneration across the spinal cord in patients with mild-moderate degenerative cervical myelopathy (DCM).

Methods

Twenty-four mild-moderate DCM and 24 healthy subjects were recruited. In patients, a T2-weighted scan was acquired at the compression site, while in all participants a T2*-weighted and diffusion-weighted scan was acquired at the cervical level (C2-C3) and in the lumbar enlargement (i.e. rostral and caudal to the site of compression). We quantified intramedullary signal changes, maximal canal and cord compression, white (WM) and grey matter (GM) atrophy, and microstructural indices from diffusion-weighted scans. All patients underwent clinical (modified Japanese Orthopaedic Association (mJOA)) and electrophysiological assessments. Regression analysis assessed associations between MRI readouts and electrophysiological and clinical outcomes.

Results

Twenty patients were classified with mild and four with moderate DCM using the mJOA scale. The most frequent site of compression was at C5-C6 level with maximum cord compression of 4.68±0.83 mm. Ten patients showed imaging evidence of cervical myelopathy. In the cervical cord, WM and GM atrophy and WM microstructural changes were evident, while in the lumbar cord only WM showed atrophy and microstructural changes. Remote cervical cord WM microstructural changes were pronounced in patients with radiological myelopathy and associated with impaired electrophysiology. Lumbar cord WM atrophy was associated with lower limb sensory impairments.

Conclusion

Tissue-specific neurodegeneration revealed by quantitative MRI, already apparent across the spinal cord in mild-moderate DCM prior to the onset of severe clinical impairments. WM microstructural changes are particularly sensitive to remote pathologically and clinically eloquent changes in DCM.
Brain lesion locations associated with secondary seizure generalization
Authors: Nordberg Janne , Schaper Frederic LWVJ. , Bucci Marco , Nummenmaa Lauri , Joutsa Juho
Published: April 2021

Background

Structural brain lesions are the most common cause of adult-onset epilepsy. The lesion location may contribute to the risk for epileptogenesis, but whether specific lesion locations are associated with a risk for secondary seizure generalization from focal to bilateral tonic-clonic seizures, is unknown.

Methods

We identified patients with a diagnosis of adult-onset epilepsy caused by an ischemic stroke or a tumor diagnosed at the Turku University Hospital in 2004-2017. Lesion locations were segmented on patient-specific MR imaging and transformed to a common brain atlas (MNI space). Both region-of-interest analyses (intersection with the cortex, hemisphere, and lobes) and voxel-wise analyses were conducted to identify the lesion locations associated with focal to bilateral tonic-clonic compared to focal seizures.

Results

We included 170 patients with lesion-induced epilepsy (94 tumors, 76 strokes). Lesions predominantly localized in the cerebral cortex (OR 2.50, 95% C.I. 1.21-5.15, p = 0.01) and right hemisphere (OR 2.22, 95% C.I. 1.17-4.20, p = 0.01) were independently associated with focal to bilateral tonic-clonic seizures. At the lobar-level, focal to bilateral tonic-clonic seizures were associated with lesions in the right frontal cortex (OR 4.41, 95% C.I. 1.44-13.5, p = 0.009). No single voxels were significantly associated with seizure type. These effects were independent of lesion etiology.

Conclusions

Our results demonstrate that lesion location is associated with the risk for secondary generalization of epileptic seizures independent of lesion etiology. These findings may contribute to identifying patients at risk for focal to bilateral tonic-clonic seizures.
Effects of BNT162b2 mRNA vaccine on Covid-19 infection and hospitalisation among older people: matched case control study for England
Authors: Mason Thomas , Whitston Matt , Hodgson Jack , Watkinson Ruth E , Lau Yiu-Shing , Abdulrazeg Omnia , Sutton Matt
Published: April 2021

Background

The BNT162b2 mRNA vaccine has been shown to be effective at preventing serious Covid-19 events in clinical trials. There is less evidence on effectiveness in real-world settings, especially for older people. The rapid roll-out of the NHS vaccination programme in England based on age thresholds offers an opportunity to make unbiased comparisons of outcomes between vaccinated and unvaccinated populations.

Methods and Findings

We matched older (aged 80-83 years) vaccine recipients with younger (aged 76-79 years) persons not yet eligible to receive the vaccine on gender, area of residence, area deprivation, health status, living arrangements, acute illness, and history of seasonal flu vaccination. We also adjusted for the over-representation of Covid-19 positive individuals in the control population because eligibility for vaccination required no Covid-19 symptoms in the previous two weeks. The study population included 170,226 individuals between the ages of 80 and 83 years from community settings outside care homes who received one dose of BNT162b2 mRNA between the 15th and 20th December 2020 and were scheduled a second dose 21 days later.

We found emergency hospital admissions were 51.0% (95% confidence interval: 19.9% to 69.5%) lower and positive Covid-19 tests were 55.2% (40.8% to 66.8%) lower for vaccinated individuals compared to matched controls 21 to 27 days after first vaccination. Emergency admissions were 75.6% (52.8% to 87.6%) lower and positive Covid-19 tests were 70.1% (55.1% to 80.1%) lower 35 to 41 days after first vaccination when 79% of participants had received a second dose within 26 days of their first dose.

Conclusions

Receipt of the BNT162b2 mRNA vaccine is effective at reducing Covid-19 hospitalisations and infections. The nationwide vaccination of older adults in England with the BNT162b2 mRNA vaccine reduced the burden of Covid-19.
Modelling to inform the COVID-19 response in Bangladesh
Authors: Ferguson Elaine A , Brum Eric , Chowdhury Anir , Chowdhury Shayan , Kundegorski Mikolaj , Mahmud Ayesha S , Purno Nabila , Sania Ayesha , Steenson Rachel , Tasneem Motahara , Hampson Katie
Published: April 2021

Background

Non-pharmaceutical interventions (NPIs) used to limit SARS-CoV-2 transmission vary in their feasibility, appropriateness and effectiveness in different contexts. In Bangladesh a national lockdown implemented in March 2020 exacerbated poverty and was untenable long-term, and a resurgence in 2021 warranted renewed NPIs.

Methods

We developed an SEIR model for Dhaka District, parameterised from literature values and calibrated to data from Bangladesh. We discussed scenarios and parameterisations with policymakers with the aid of an interactive app. These discussions guided modelling of lockdown and two post-lockdown measures considered feasible to deliver; symptoms-based household quarantining and compulsory mask-wearing. We examined how testing capacity affects case detection, and compared NPI scenarios on deaths, hospitalisations relative to capacity, working days lost, and cost-effectiveness.

Results

Lockdowns alone were predicted to delay the first epidemic peak but could not prevent overwhelming of the health service and were costly in lost working days. Impacts of post-lockdown interventions depended heavily on compliance. Assuming 80% compliance, symptoms-based household quarantining alone could not prevent hospitalisations exceeding capacity, whilst mask-wearing prevented overwhelming health services and was cost-effective given masks of high filtration efficiency. Combining masks with quarantine increased their impact. Even at maximum testing capacity, confirmed cases far underestimate total cases. Recalibration to surging cases in 2021 suggests potential for another wave later in 2021, dependent on uncertainties in case reporting and immunity.

Conclusions

Masks and symptoms-based household quarantining synergistically prevent transmission, and are cost-effective in Bangladesh. Our interactive app was valuable in supporting decision-making, with mask-wearing being mandated early, and community teams being deployed to support quarantining across Dhaka. These measures likely contributed to averting the worst public health impacts, but delivering an effective response at scale has been challenging. Messaging to increase compliance with mask-wearing and quarantine is needed to reduce the risk and impacts from another wave.
The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and body mass index: mendelian randomization study
Authors: Zhao Sizheng Steven , Holmes Michael V , Zheng Jie , Sanderson Eleanor , Carter Alice R
Published: April 2021

Objective

To estimate the causal relationship between educational attainment – as a proxy for socioeconomic inequality – and risk of RA and quantify the roles of cigarette smoking and body mass index (BMI) as potential mediators.

Methods

Using the largest genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) study of genetically predicted educational attainment (instrumented using 1265 variants from 766,345 individuals) and RA (14,361 cases, 43,923 controls). We used two-step MR to quantify the proportion of education’s effect on RA mediated by smoking exposure (as a composite index capturing duration, heaviness and cessation, using 124 variants from 462,690 individuals) and BMI (517 variants, 681,275 individuals), and multivariable MR to estimate proportion mediated by both factors combined.

Results

Each standard deviation (SD) increase in educational attainment (4.2 years of schooling) was protective of RA (OR 0.37; 95%CI 0.31, 0.44). Higher educational attainment was also protective for smoking exposure (β= -0.25 SD; 95%CI -0.26, -0.23) and BMI (β= -0.27 SD (∼1.3kg/m2); 95%CI -0.31, - 0.24). Smoking mediated 24% (95%CI 13%, 35%) and BMI 17% (95%CI 11%, 23%) of the total effect of education on RA. Combined, the two risk factors explained 47% (95%CI 11%, 82%) of the total effect.

Conclusion

Higher educational attainment has a protective effect on RA risk. Interventions to reduce smoking and excess adiposity at a population level may reduce this risk, but a large proportion of education’s effect on RA remains unexplained. Further research into other risk factors that act as potentially modifiable mediators are required.

Key messages

Genetically predicted higher educational attainment – as a proxy for socioeconomic position – is protective for RA.

24% of this effect was mediated by smoking behaviour and 17% by body mass index.

Efforts to reduce smoking and excess adiposity would help mitigate against socioeconomic inequalities in RA
Multiplex SARS-CoV-2 Genotyping PCR for Population-Level Variant Screening and Epidemiologic Surveillance
Authors: Wang Hannah , Miller Jacob A. , Verghese Michelle , Sibai Mamdouh , Solis Daniel , Mfuh Kenji O. , Jiang Becky , Iwai Naomi , Mar Marilyn , Huang ChunHong , Yamamoto Fumiko , Sahoo Malaya K. , Zehnder James , Pinsky Benjamin A.
Published: April 2021

Background

Emergence of SARS-CoV-2 variants with concerning phenotypic mutations is of public health interest. Genomic surveillance is an important tool for pandemic response, but many laboratories do not have the resources to support population-level sequencing. We hypothesized that a spike genotyping nucleic acid amplification test (NAAT) could facilitate high-throughput variant surveillance.

Methods

We designed and analytically validated a one-step multiplex allele-specific reverse transcriptase polymerase chain reaction (RT-qPCR) to detect three non-synonymous spike protein mutations (L452R, E484K, N501Y). Assay specificity was validated with next-generation whole-genome sequencing. We then screened a large cohort of SARS-CoV-2 positive specimens from our San Francisco Bay Area population.

Results

Between December 1, 2020 and March 1, 2021, we screened 4,049 unique infections by genotyping RT-qPCR, with an assay failure rate of 2.8%. We detected 1,567 L452R mutations (38.7%), 34 N501Y mutations (0.84%), 22 E484K mutations (0.54%), and 3 (0.07%) E484K+N501Y mutations. The assay had near-perfect (98-100%) concordance with whole-genome sequencing in a validation subset of 229 specimens, and detected B.1.1.7, B.1.351, B.1.427, B.1.429, B.1.526, and P.2 variants, among others. The assay revealed rapid emergence of L452R in our population, with a prevalence of 24.8% in December 2020 that increased to 62.5% in March 2021.

Conclusions

We developed and clinically implemented a genotyping RT-qPCR to conduct high-throughput SARS-CoV-2 variant screening. This approach can be adapted for emerging mutations and immediately implemented in laboratories already performing NAAT worldwide using existing equipment, personnel, and extracted nucleic acid.

Summary / Key Points

Emergence of SARS-CoV-2 variants with concerning phenotypes is of public health interest. We developed a multiplex genotyping RT-qPCR to rapidly detect L452R, E484K, and N501Y with high sequencing concordance. This high-throughput alternative to resource-intensive sequencing enabled surveillance of L452R emergence.
MYCdosage compensation is mediated by miRNA-transcription factor interactions in aneuploid cancer
Authors: Acón ManSai , Geiß Carsten , Torres-Calvo Jorge , Bravo-Estupiñan Diana , Oviedo Guillermo , Arias-Arias Jorge L , Rojas-Matey Luis A , Baez Edwin , Vásquez-Vargas Gloriana , Oses-Vargas Yendry , Guevara-Coto José , Segura-Castillo Andrés , Siles-Canales Francisco , Quirós-Barrantes Steve , Régnier-Vigouroux Anne , Mendes Pedro , Mora-Rodríguez Rodrigo
Published: April 2021

We hypothesize that dosage compensation of critical genes arises from systems-level properties for cancer cells to withstand the negative effects of aneuploidy. We identified several candidate genes in cancer multi-omics data and developed a biocomputational platform to construct a mathematical model of their interaction network with miRNAs and transcription factors, where the property of dosage compensation emerged forMYCand was dependent on the kinetic parameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated with a novel genetic tug-of-war technique by overexpressing an exogenousMYCleading to over-expression of the three microRNAs involved and down-regulation of endogenousMYC.In addition,MYCoverexpression or inhibition of its compensating miRNAs led to dosage-dependent cytotoxicity inMYC-amplified colon cancer cells. Finally, we identified negative correlation ofMYCdosage compensation with patient survival in TCGA breast cancer patients, highlighting the potential of this mechanism to prevent aneuploid cancer progression.

Highlights

The systems-level property of gene dosage-compensation emergesin silicoin miRNA-transcription factor networks depending on the kinetic parameters of its interactions.

We established a criterion to identify compensated candidate genes with low variation in expression despite high copy number variation.

BioNetUCR is a novel biocomputational platform to model miRNA-transcription factor interactions

We present a novel genetic tug-of-war technique to experimentally validate gene dosage compensation at the transcriptional level.

Abstract Figure
METTL9 regulates N1-histidine methylation of zinc transporters to promote tumor growth
Authors: Lv Mengyue , Cao Dan , Zhang Liwen , Hu Chi , Li Shukai , Zhang Panrui , Zhu Lianbang , Yi Xiao , Li Chaoliang , Yang Alin , Yang Zhentao , Zhu Yi , Zhang Kaiguang , Pan Wen
Published: April 2021

Methyltransferase like 9 (Mettl9) is a member of the methyltransferase like protein family which is characterized by the presence of binding domains for S-adenosyl methionine, (SAM), a co-substrate for methylation reactions. Despite METTL9 is predicted to be a methyltransferase, its enzymatic activity, substrate specificities and biological functions are still poorly characterized. In this study, we revealed a tumor-promoting role for METTL9. We found that deletion ofMettl9in tumor cells suppresses tumor growth and elicits potent anti-tumor immunity. Mechanistically, METTL9 is a N1-histidine methyltransferase which methylates the histidine residues of a x-His-x-His (xHxH) motif on the substrates. This motif is found extensively in zinc transporter families SLC39s and SLC30s, particularly in SLC39A7. Deletion ofMettl9impairs cytoplasmic zinc homeostasis, resulting in an altered gene expression program with increased endoplasmic reticulum (ER) stress and reduced cell cycle. Mutation of key METTL9 catalyzed methylhistidine residues of SLC39A7 impairs cytoplasmic zinc homeostasis and affects cell growth as well. Notably,METTL9expression is increased in some cancer types and its higher expression is associated with worse clinical outcomes, particularly in liver and pancreatic cancer. In summary, our work identifiedMETTL9as a potential new oncogene and its mediated methylation is of regulatory importance. Identifying selective and potent small-molecule inhibitors of METTL9 could thus represent novel therapeutic strategy for anti-proliferative cancer drugs.
Design and evaluation of mobile monitoring campaigns for air pollution exposure assessment in epidemiologic cohorts
Authors: Blanco Magali N. , Doubleday Annie , Austin Elena , Marshall Julian D. , Seto Edmund , Larson Timothy , Sheppard Lianne
Published: April 2021

Mobile monitoring campaigns to estimate long-term air pollution levels are becoming increasingly common. Still, many campaigns have not conducted temporally-balanced sampling, and few have looked at the implications of such study designs for epidemiologic exposure assessment. We carried out a simulation study of fixed-site air quality monitors to better understand how different mobile monitoring designs involving short-term stationary measurements at fixed locations impact the resulting exposure surfaces. We used Monte Carlo resampling to simulate three archetypal monitoring designs using oxides of nitrogen (NOx) monitoring data from 69 regulatory sites in California: a year-around Balanced Design that sampled during all seasons of the year, days of the week, and all or various hours of the day; a temporally reduced Rush Hours Design; and a temporally reduced Business Hours Design. We evaluated the performance of each design’s land use regression prediction model. The Balanced Design consistently yielded the most accurate annual averages; while the reduced Rush Hours and Business Hours Designs generally produced more biased results. A temporally-balanced sampling design is crucial for mobile monitoring campaigns aiming to assess accurate long-term exposure in epidemiologic cohorts.

Synopsis

Air pollution mobile monitoring campaigns rarely conduct temporally balanced sampling. We show that this results in biased annual average exposure estimates.