bluuebunny/crossref_metadata_2025 huggingface dataset:
Telephone-based depression self-management in Hispanic adults with epilepsy: a pilot randomized controlled trial
Authors: Spruill Tanya M , Friedman Daniel , Diaz Laura , Butler Mark J , Goldfeld Keith S , O’Kula Susanna , Montesdeoca Jacqueline , Payano Leydi , Shallcross Amanda J , Kaur Kiranjot , Tau Michael , Vazquez Blanca , Jongeling Amy , Ogedegbe Gbenga , Devinsky Orrin
Published: May 2021

Depression is associated with adverse outcomes in epilepsy but is undertreated in this population. Project UPLIFT, a telephone-based depression self-management program, was developed for adults with epilepsy and has been shown to reduce depressive symptoms in English-speaking patients. There remains an unmet need for accessible mental health programs for Hispanic adults with epilepsy. The purpose of this study was to evaluate the feasibility, acceptability, and effects on depressive symptoms of a culturally adapted version of UPLIFT for the Hispanic community. Hispanic patients with elevated depressive symptoms (n = 72) were enrolled from epilepsy clinics in New York City and randomized to UPLIFT or usual care. UPLIFT was delivered in English or Spanish to small groups in eight weekly telephone sessions. Feasibility was assessed by recruitment, retention, and adherence rates and acceptability was assessed by self-reported satisfaction with the intervention. Depressive symptoms (PHQ-9 scores) were compared between study arms over 12 months. The mean age was 43.3±11.3, 71% of participants were female and 67% were primary Spanish speakers. Recruitment (76% consent rate) and retention rates (86–93%) were high. UPLIFT participants completed a median of six out of eight sessions and satisfaction ratings were high, but rates of long-term practice were low. Rates of clinically significant depressive symptoms (PHQ-9 ≥5) were lower in UPLIFT versus usual care throughout follow-up (63% vs. 72%, 8 weeks; 40% vs. 70%, 6 months; 47% vs. 70%, 12 months). Multivariable-adjusted regressions demonstrated statistically significant differences at 6 months (OR = 0.24, 95% CI, 0.06–0.93), which were slightly reduced at 12 months (OR = 0.30, 95% CI, 0.08–1.16). Results suggest that UPLIFT is feasible and acceptable among Hispanic adults with epilepsy and demonstrate promising effects on depressive symptoms. Larger trials in geographically diverse samples are warranted.
Acute Fixation of Displaced Intra-articular Calcaneus Fractures Is Safe Using the Sinus Tarsi Approach
Authors: Joseph Noah M. , Benedick Alex , McMellen Christopher , Napora Joshua , Wetzel Robert , Sontich John , Ochenjele George
Published: May 2021

Objective:

To analyze the correlation between surgical timing and outcomes for calcaneus fractures treated using a sinus tarsi approach (STA).

Setting:

Single Level-1 trauma center.

Design:

Retrospective.

Patients/Participants:

Seventy consecutive intra-articular calcaneus fractures (OTA/AO 82C; Sanders II-IV) treated operatively using STA with a minimum of 1-year follow-up.

Intervention:

Open management using STA.

Main Outcome Measurement:

Surgery timing, wound complications, American Orthopaedic Foot and Ankle Society ankle and hindfoot and Patient-reported Outcomes Measurement System scores.

Results:

Patients were primarily men (68.6%) averaging 46 years (range, 18–77 years). Nineteen (27%) were obese, 27 (38.6%) were smokers, and 3 (4.3%) were diabetic, and 10 (14.3%) had open fractures. Sanders III fracture patterns were most common (45.7%). Mean time to surgery was 4.9 days (range, 0–23 days). Three patients (4.2%) developed postoperative infections requiring surgical debridement and antibiotics. Forty patients (57%) underwent operative repair within 72 hours of injury, 9 (22.5%) of which had open fractures. Of this group, only one patient developed wound necrosis. Restoration of Bohler angle and angle of Gissane and reductions in calcaneal varus angle and heel width were achieved (all P < 0.001). No differences in Ankle Society ankle and hindfoot or Patient-reported Outcomes Measurement System scores were noted between patients treated within or beyond 72 hours from injury.

Conclusion:

Intra-articular calcaneus fractures can be treated acutely within 72 hours of injury using STA with minimal wound complications and without compromising short-term functional outcome.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Hidden in plain sight: the (other) danger of COVID-19
Authors: Pikkel Yoav Yechezkel , Duek Ori Samuel , Ben Naftali Yeela , Link Yuval , Khayr Majd , Ullmann Yehuda
Published: May 2021

The Novel Coronavirus disease (COVID-19) first emerged in Wuhan province, China, in late November 2019 and changed public healthcare perception. It has caused a significant decline in attendance to outpatient clinics. However, other diseases have not stopped, including malignant melanoma. Survey of the number of visits to plastic surgery outpatient clinic during the first lockdown in Israel concerning malignant melanoma was compared to the same months in the previous years. We assessed the number of visits to the oncology department during 2020 compared to the number of visits and treatment protocols for malignant melanoma. During the first lockdown, the attendance at the plastic surgery outpatient clinic and ambulatory surgery decreased significantly (P = 0.002), both in excisions of suspected malignant melanoma and malignant melanoma follow-ups (P = 0.019 and P = 0.035, respectively). The last third of 2020 (from September to December) had shown a significant rise in new protocols commenced (P < 0.001). This rise in the final third of the year was not noted in 2018 or 2019. These data clearly show the rise in advanced and metastatic malignant melanoma cases due to refraining from medical follow-ups and treatments during the COVID-19 pandemic. Diseases other than COVID-19 have not vanished, and continue to treat those diseases. Ignoring malignant melanoma treatment because of COVID-19 and vice-versa will not benefit our patients.
Does a balanced colloid decrease perioperative blood loss in paediatric cardiac surgery
Authors: Willems Ariane , De Groote Françoise , Schmartz Denis , Fils Jean-François , Van der Linden Philippe
Published: May 2021

BACKGROUND

Unbalanced fluid solutions cause metabolic acidosis and could be associated with impaired coagulation and increased blood loss.

OBJECTIVE

To investigate whether the use of a balanced colloid compared with a saline colloid for peri-operative fluid therapy in children undergoing cardiac surgery is associated with decreased blood loss and exposure to blood products.

DESIGN

Double-blinded randomised controlled trial.

SETTING

Tertiary children's hospital from 2013 to 2016.

PATIENTS

Children older than 29 days and younger than 3 years admitted for cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria were emergency cardiac surgery, moribund (American Society of Anesthesiologists 5), Jehovah's witnesses, coagulopathy, renal failure, liver injury, intracranial haemorrhage and electrolyte disturbances. From the 128 patients eligible, 88 were included in the study.

INTERVENTION

Random assignment of patients to either a saline colloid (6% hydroxyethyl starch 130/0.4 in 0.9% NaCl) or a balanced-electrolyte colloid (6% hydroxyethyl starch 130/0.4 in an isotonic solution) for CPB priming and intra- and postoperative fluid therapy during the first postoperative 48 h.

MAIN OUTCOME MEASURE

The primary outcome measure was calculated blood loss until the third postoperative day (POD3).

RESULTS

A total of 44 patients were included in each study arm. Calculated blood loss at POD3 was not significantly different between the groups (saline colloid 19.9 [IQR 13.8 to 26.1] ml kg−1 versus balanced colloid 15.9 [IQR 9.0 to 25.3 ml kg−1], P = 0.409). Secondary outcomes related to bleeding, exposure to blood products and coagulation were not different between groups. There was also no difference in length of mechanical ventilation, intensive care and hospital length of stay between groups.

CONCLUSION

The use of a balanced colloid for peri-operative fluid therapy compared with a saline one is not associated with decreased blood loss or exposure to blood products.

TRIAL REGISTRATION

EudraCT identifier: 2012-006034-17 and ClinicalTrial.gov identifier: NCT02584868.
Within-visit and between-visit intra-individual blood pressure variability in an unselected adult population from rural China
Authors: Fan Wei-guo , Wang Wen-ying , Meng Ya-xing , Sharman James E. , Parati Gianfranco , Campbell Norm R.C. , Su Hai
Published: May 2021

Objective:

To assess the association between the variability of blood pressure (BP) readings within an initial clinic visit, the variability within subsequent visits and the variability between visits over 1 week in a general population.

Methods:

This study included 1401 adult residents, who were not taking antihypertensive drugs, having BP measurements at three visits over 1 week. The difference between maximal and minimal BP readings (ΔBP), ΔBP/BPm (the mean BP value in a visit), the standard deviation (SD) and coefficient of variation (coefficient of variation = SD × 100/mean) of three BP values in each visit were used to estimate the within-visit BP variability (BPV). The SD and coefficient of variation of all nine BP readings over the three visits were calculated as SD9 or CV9 to reflect the overall BPV during the study visits. The SD and coefficient of variation on the mean BP values (BPm) of three visits were computed as SD-3 or CV-3, whereas the difference between maximal and minimal BP in three visits was computed as ΔBP-3 to estimate visit-to-visit BPV. The average BP or HR was the mean values of nine BP or HR readings over three visits.

Results:

The systolic and diastolic mean BP (SBP and DBP) decreased from the first to the third visit. The ΔBP, SD and coefficient of variation for both SBP and DBP at the first visit were positively and significantly correlated with the corresponding variables computed at the second and third visits, as well as with overall BPV (ΔBP9, SD9 and CV9). A positive correlation was also found between overall BPV and visit-to visit BPV (SD-3, CV-3 and ΔBP9). Multivariate analysis showed: no association between average SBP and systolic coefficient of variation or ΔBP/BPm but a negative association between average DBP and coefficient of variation or ΔBP/BPm for DBP at the first visit, DBP-3 and DBP9. Age was positively correlated with coefficient of variation or ΔBP/BPm for SBP at the first visit, SBP-3 and SBP9, and correlated with coefficient of variation and ΔBP/BPm for DBP only at the first visit.

Conclusion:

In a general population, within-visit BPV at an initial visit is associated with within-visit BPV at subsequent visits and with visit-to-visit BPV over three visits within 1 week.
The role of environment in the pathogenesis of keratoconus
Authors: de Azevedo Magalhães Otávio , Gonçalves Mauro Cabral , Gatinel Damien
Published: May 2021

Purpose of review

This study was conducted to demonstrate the importance of the environment in keratoconus (KC) genesis.

Recent findings

Genetic-related connective tissue disorders demonstrate the inconsistency of theories regarding KC pathogenesis since no corneal steepening was observed in the majority of these patients. Despite recent advances and decades of research into the genetics of KC, the identification of disease-causing KC genes has been frustrating. Variants found based on genome-wide and next-generation sequencing only seem to account for a small number of cases or play a limited role in KC pathogenesis.

The literature shows that mechanical manipulation may be the common underlying factor or the indispensable act precipitating the cascade of events leading to permanent corneal deformation. Hence, ophthalmologists have the opportunity to increase patient awareness about eye manipulation repercussions and treatment for ocular surface disorders.

Video abstract

http://links.lww.com/COOP/A42
Update on corneal collagen crosslinking for ectasia
Authors: Pasha Hamza , Palazzolo Laura , Prakash Gaurav , Jhanji Vishal
Published: May 2021

Purpose of review

Corneal collagen crosslinking (CXL) is a minimally invasive treatment that can stabilize corneal ectatic disorders including keratoconus, pellucid marginal degeneration, or postrefractive surgery ectasia. The benefits of CXL have been well documented. New research is focused on modifying current treatment protocols with the goals of maximizing corneal stability while also shortening overall procedure time.

Recent findings

Accelerated CXL protocols have the goal of delivering the same ultraviolet A intensity as conventional protocols, but over a shorter time period. Accelerated protocols have shown success to date, but there are concerns for long-term corneal stability. Pulsed protocols may increase the long-term efficacy of the accelerated designs. In addition, transepithelial crosslinking protocols have been designed with the goal of reducing postoperative pain and lower the risk of infectious complications of epithelial-off conventional protocols.

Newer CXL protocols attempt to make the procedure safer and more effective. Current research is promising, but long-term studies are essential to understand how the new protocols may affect corneal stability.
Evaluating Arterial Blood Flow Limitation Using Muscle Oxygenation and Cycling Power
Authors: Arnold Jem , Yogev Assaf , Koehle Michael S.
Published: May 2021

Objective:

To explore the combination of measuring muscle oxygenation with near-infrared spectroscopy (NIRS) and cycling power during provocative incremental exercise for the detection of iliac arterial blood flow limitation (IAFL) in an otherwise healthy, well-trained cyclist.

Design:

Case report and methodological pilot study.

Setting:

University research setting.

Patient:

A well-trained amateur competitive male cyclist, aged 31 years, presenting with symptoms consistent with IAFL, but in whom diagnostic imaging was equivocal.

Interventions:

Four ramp incremental cycling tests performed on separate days to exercise intolerance, in a randomized order, in either typical race position (RP) or modified upright position (UP).

Main Outcome:

A novel ratio of unilateral cycling power to NIRS-derived muscle oxygenation termed “power-deoxygenation factor” was measured during provocative incremental exercise and compared with other NIRS-derived measures of vascular responsiveness and performance outcomes across the 2 body position conditions.

Results:

The power–deoxygenation factor was able to show clinically important, progressive differences between the affected and unaffected limbs, coinciding with worsening performance impairments related to the body position that were not detected with traditional measures of vascular responsiveness taken after exercise.

Conclusions:

This method was used to detect bilateral differences consistent with IAFL in a cyclist where traditional diagnostic criteria were equivocal, but subsequent intraoperative findings confirmed the diagnosis. A similar screening test could be performed noninvasively and without requiring specialized medical care. Future work should investigate the validity and sensitivity of this methodology to improve the ability to identify and monitor athletes with IAFL.
Modified AngioVac System use With Extracorporeal Membrane Oxygenation in a Child With Fontan Thrombosis
Authors: Priest John R. , Brown Mark , Choi Daniel , Thiagarajan Ravi , Roy Nathalie , Esch Jesse , Moynihan Katie M.
Published: May 2021

The AngioVac System (AVS) extracts venous and pulmonary artery (PA) thrombi. We report modified use of the second-generation AVS with concurrent venoarterial extracorporeal membrane oxygenation (VA-ECMO) in a 10-year-old, 23 kg patient with failing Fontan circulation due to acute-on-chronic Fontan and PA thrombosis. Emergent femoral VA-ECMO was initiated for profound hypoxemia during cardiac catheterization. Fluoroscopy-guided thrombo-embolectomy was performed with AVS components. A two-venous limb inflow cannulation strategy was used; the AngioVac cannula (AVC) was positioned in the central PA and joined to the existing ECMO venous-limb. Thrombus extraction proceeded by clamping the ECMO venous-limb with the existing VA-ECMO centrifugal pump generating negative pressure to the AVC. Extracorporeal membrane oxygenation arterial-limb access was used for blood return. Settings to avoid cavitation were a maximal negative pressure of 100 mmHg using <3500 RPMs. To access the branch PAs, the AVC was replaced by a custom-modified 17 Fr arterial ECMO cannula. Clot retrieval was sufficient for improved clinical status enabling ECMO discontinuation within 24-hours, and discharge home 26-days later.

This is the first description of successful subtotal thrombo-embolectomy with AVS components in a child with Fontan physiology concurrently supported on VA-ECMO, using one centrifugal pump. Although feasible, circuit modifications and close monitoring are required to avoid complications.
Hemodynamic monitoring in cardiogenic shock
Authors: VanDyck Tyler J. , Pinsky Michael R.
Published: May 2021

Purpose of review

Cardiogenic shock remains a major cause of mortality today. With recent advancements in invasive mechanical support strategies, reperfusion practice, and a new classification scheme is proposed for cardiogenic shock, an updated review of the latest hemodynamic monitoring techniques is important.

Recent findings

Multiple recent studies have emerged supporting the use of pulmonary artery catheters in the cardiogenic shock population. Data likewise continues to emerge on the use of echocardiography and biomarker measurement in the care of these patients.

The integration of multiple forms of hemodynamic monitoring, spanning noninvasive and invasive modalities, is important in the diagnosis, staging, initial treatment, and subsequent management of the cardiogenic shock patient.
Applications of artificial intelligence in prostate cancer imaging
Authors: Baltzer Pascal A.T. , Clauser Paola
Published: May 2021

Purpose of review

The purpose of this review was to identify the most recent lines of research focusing on the application of artificial intelligence (AI) in the diagnosis and staging of prostate cancer (PCa) with imaging.

Recent findings

The majority of studies focused on the improvement in the interpretation of bi-parametric and multiparametric magnetic resonance imaging, and in the planning of image guided biopsy. These initial studies showed that AI methods based on convolutional neural networks could achieve a diagnostic performance close to that of radiologists. In addition, these methods could improve segmentation and reduce inter-reader variability. Methods based on both clinical and imaging findings could help in the identification of high-grade PCa and more aggressive disease, thus guiding treatment decisions. Though these initial results are promising, only few studies addressed the repeatability and reproducibility of the investigated AI tools. Further, large-scale validation studies are missing and no diagnostic phase III or higher studies proving improved outcomes regarding clinical decision making have been conducted.

AI techniques have the potential to significantly improve and simplify diagnosis, risk stratification and staging of PCa. Larger studies with a focus on quality standards are needed to allow a widespread introduction of AI in clinical practice.
Evaluation of Drug-Related Risk Behaviors Among Females Diagnosed With Early Syphilis in New York State (Excluding New York City), 2013 to 2018
Authors: Drame Fanta , Bomma Srikanth , Miranda Wilson , Gelberg Kitty , Hart-Malloy Rachel
Published: May 2021

This evaluation describes an increase in reported drug-related risk behaviors among females who are diagnosed with early syphilis over a 5-year span in New York State, excluding New York City. Integrating sexually transmitted infection prevention efforts with harm reduction services may help decrease syphilis rates in areas where drug-related risk behavior rates are high.
Case Series: High-resolution Optical Coherence Tomography as an Optical Biopsy in Ocular Surface Squamous Neoplasia
Authors: Aboumourad Rami J. , Galor Anat , Karp Carol L.
Published: May 2021

SIGNIFICANCE

Ocular surface squamous neoplasias are superficial tumors of the cornea and conjunctiva that can be sight threatening if neglected. Therefore, accurate noninvasive diagnostic modalities are needed.

PURPOSE

The purpose of this case series was to describe the hallmark features of ocular surface squamous neoplasia on high-resolution optical coherence tomography (HR-OCT) imaging and its use in the evaluation and management of superficial ocular tumors.

CASE SERIES

Five eyes of four patients with ocular surface squamous neoplasia are described. Whereas two eyes displayed the classic clinical features of ocular surface squamous neoplasia, three of the five eyes had more subtle atypical features. However, all shared features on HR-OCT of epithelial thickening and hyperreflectivity with abrupt transitions between normal and abnormal tissue, classic features of ocular surface squamous neoplasia. All lesions ultimately underwent incisional or excisional biopsy and were confirmed to be ocular surface squamous neoplasia on histopathology.

CONCLUSIONS

Ocular surface squamous neoplasia may present as a classic tumor but can also have subtle features or masquerade. Accurate methods to diagnose and manage patients with ocular surface squamous neoplasia are necessary. With recent advancements in technology, HR-OCT has been demonstrated to accurately identify ocular surface squamous neoplasia with the repeatable optical findings of (1) epithelial thickening, (2) epithelial hyperreflectivity, and (3) abrupt transition zone between normal and abnormal tissue. This case series demonstrates how HR-OCT can help provide an optical biopsy to guide appropriate diagnosis and management of this neoplastic lesion.
A double negative post-transcriptional regulatory circuit underlies the virgin behavioral state
Authors: Garaulet Daniel L. , Moro Albertomaria , Lai Eric C.
Published: May 2021

The survival and reproductive success of animals depends on the ability to harmonize their external behaviors with their internal states. For example, females conduct numerous social programs that are distinctive to virgins, compared to post-mated and/or pregnant individuals. InDrosophila, the fact that this post-mating switch is initiated by seminal factors implies that the default state is virgin. However, we recently showed that loss of miR-iab-4/8-mediated repression of the transcription factor Homothorax (Hth) within the abdominal ventral nerve cord (VNC) causes virgin females to execute mated behaviors. To elucidate new components of this post-transcriptional regulatory circuit, we used genomic analysis ofmir-iab-4/8deletion andhth-miRNA binding site mutants (hth[BSmut]) to elucidatedoublesex(dsx) as a critical downstream factor. While Dsx has mostly been studied during sex-specific differentiation, its activities in neurons are little known. We find that accumulation of Dsx in the CNS is highly complementary to Hth, and downregulated in miRNA/hth[BSmut]mutants. Moreover, virgin behavior is highly dose-sensitive to developmentaldsxfunction. Strikingly, depletion of Dsx in SAG-1 cells, a highly restricted set of abdominal neurons, abrogates female virgin conducts in favor of mated behavioral programs. Thus, a double negative post-transcriptional pathway in the VNC (miR-iab-4/8 -| Hth -| Dsx) specifies the virgin behavioral state.
Risk of vaccine preventable diseases in UK migrants: a serosurvey and concordance analysis, 2020
Authors: Gogoi Mayuri , Martin Christopher A. , Wiselka Martin J. , Gardener Judi , Ellis Kate , Renals Valerie , Lewszuk Adam J. , Hargreaves Sally , Pareek Manish
Published: May 2021

We conducted a serosurvey in 2020, amongst 149 adult migrants living in the United Kingdom, to determine seroprotection rates for measles, varicella zoster, and rubella. Findings suggest a gap in seroprotection against measles (89.3%). Younger migrants and those from Europe and Central Asia may be more susceptible; self-reported vaccine/disease status is a poor predictor of seroprotection. Understanding factors associated with seroprotection among migrants is critical for informing the delivery of SARS-CoV-2 vaccine.
Multicentric Evaluation of a Novel Point of Care Electrochemical ELISA Platform for SARS-CoV-2 Specific IgG and IgM Antibody Assay
Authors: Kumar Vinay , Ghosh Kanad , Chandran Anagha , Panwar Sachin , Bhat Ananthram , Konaje Shreenivas , Das Saroj , Srikanta S , Jaganathan Latha , Prasad Sujay , Venkatesh D B , Shivaram C. , Krishnaswamy P R , Bhat Navakanta
Published: May 2021

New diagnostics technologies for the efficient detection and quantification of SARS-CoV-2 Antibodies is very crucial to manage the COVID-19 pandemic, especially in the context of emerging vaccination paradigms. Herein, we report on a novel point-of-care Electrochemical ELISA platform with disposable screen printed electrodes functionalized with SARS-CoV-2 Spike Glycoprotein S1, to enable fast and accurate quantitative estimation of total antibody concentration (IgG and IgM) in clinical samples. The quantification is performed with a comparison of electrochemical redox current against the current produced by the spiked monoclonal antibodies with known concentration. The assay is validated through multicentric evaluation against 3 different FDA authorized Laboratory standard techniques, using both EDTA whole blood and serum samples. We demonstrate that the proposed assay has excellent sensitivity and specificity, making it a suitable candidate for epidemiological surveys and quantification of antibodies in COVID-19 vaccination programs.
Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
Authors: McNaughton Anna L , Paton Robert S , Edmans Matthew , Youngs Jonathan , Wellens Judith , Phalora Prabhjeet , Fyfe Alex , Belij-Rammerstorfer Sandra , Bolton Jai S , Ball Jonathan , Carnell George , Dejnirattisai Wanwisa , Dold Christina , Eyre David W , Hopkins Philip , Howarth Alison , Kooblall Kreepa , Klim Hannah , Leaver Susannah , Lee Lian , López-Camacho César , Lumley Sheila F , Macallan Derek , Mentzer Alexander J , Provine Nicholas , Ratcliff Jeremy , Slon-Compos Jose , Skelly Donal , Stolle Lucas , Supasa Piyada , Temperton Nigel , Walker Chris , Wang Beibei , Wyncoll Duncan ,   OPTIC consortium,   SNBTS consortium, Simmonds Peter , Lambe Teresa , Baillie Kenneth , Semple Malcolm G , Openshaw Peter IM ,   ISARIC4C Investigators, Obolski Uri , Turner Marc , Carroll Miles , Mongkolsapaya Juthathip , Screaton Gavin , Kennedy Stephen H , Jarvis Lisa , Barnes Eleanor , Dunachie Susanna , Lourenço José , Matthews Philippa C , Bicanic Tihana , Klenerman Paul , Gupta Sunetra , Thompson Craig P
Published: May 2021

It is unclear whether prior endemic coronavirus infections affect COVID-19 severity. Here, we show that in cases of fatal COVID-19, antibody responses to the SARS-COV-2 spike are directed against epitopes shared with endemic beta-coronaviruses in the S2 subunit of the SARS-CoV-2 spike protein. This immune response is associated with the compromised production of ade novoSARS-CoV-2 spike response among individuals with fatal COVID-19 outcomes.
The Triangulation WIthin A STudy (TWIST) framework for causal inference within Pharmacogenetic research
Authors: Bowden Jack , Pilling Luke C. , Türkmen Deniz , Kuo Chia-Ling , Melzer David
Published: May 2021

In this paper we review the methodological underpinnings of the general pharmacogenetic approach for uncovering genetically-driven treatment effect heterogeneity. This typically utilises only individuals who are treated and relies on fairly strong baseline assumptions to estimate what we term the ‘genetically moderated treatment effect’ (GMTE). When these assumptions are seriously violated, we show that a robust but less efficient estimate of the GMTE that incorporates information on the population of untreated individuals can instead be used. In cases of partial violation, we clarify when Mendelian randomization and a modified confounder adjustment method can also yield consistent estimates for the GMTE. A decision framework is then described to decide when a particular estimation strategy is most appropriate and how specific estimators can be combined to further improve efficiency. Triangulation of evidence from different data sources, each with their inherent biases and limitations, is becoming a well established principle for strengthening causal analysis. We call our framework ‘Triangulation WIthin a STudy’ (TWIST)’ in order to emphasise that an analysis in this spirit is also possible within a single data set, using causal estimates that are approximately uncorrelated, but reliant on different sets of assumptions. We illustrate these approaches by re-analysing primary-care-linked UK Biobank data relating to CYP2C19 genetic variants, Clopidogrel use and stroke risk, and data relating to APOE genetic variants, statin use and Coronary Artery Disease.
Hearing aids reduce daily-life fatigue and increase social activity: a longitudinal study
Authors: Holman Jack A. , Drummond Avril , Naylor Graham
Published: May 2021

People with hearing loss experience fatigue, and it is unknown whether this is alleviated by treatment with hearing aids. The objective of this study was to address this issue, and to investigate the possible concomitant effect of hearing-aid fitting on activity levels. An intervention group (n=53) who were due to be fitted with their first ever hearing aid(s) and a control group (n=53) who had hearing loss but no change in hearing aid status completed a battery of self-report outcome measures four times: once before fitting, and at two weeks, three months and six months post fitting. Self-report outcome measures at each assessment captured fatigue, listening effort, hearing handicap, auditory lifestyle, social participation restrictions and work, social and physical activity levels. Hearing-aid fitting led to a significant reduction in listening-related fatigue, but not general fatigue, in the intervention group compared to the control group. Additionally, social activity level increased and social participation restriction decreased significantly after hearing aid fitting in the intervention group compared to the control group. No significant interaction was found between working status and change in listening-related fatigue score. This study is the first to make longitudinal measurement of fatigue before and after first-ever hearing aid fitting and to identify an increase in social activity level after hearing aid fitting. These findings have important implications for future research and the clinical practice of hearing aid fitting.
Prognostic significance of protein-coding and long non-coding RNA expression profile in T-cell acute lymphoblastic leukemia
Authors: Verma Deepak , Kapoor Shruti , Sharma Disha , Singh Jay , Sharma Gunjan , Kumari Sarita , Arora Mohit , Bakhshi Sameer , Seth Rachna , Nayak Baibaswata , Sharma Atul , Pramanik Raja , Palanichamy Jayanth Kumar , Sivasubbu Sridhar , Scaria Vinod , Kumar Rajive , Chopra Anita
Published: May 2021

T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy associated with poor outcome. To unravel gene-expression profile of immunophenotypic subtypes of T-ALL, we did transcriptome analysis in 35 cases. We also analyzed the prognostic relevance of 23 targets: protein-coding genes, histone modifiers and long non-coding RNA (lncRNA) expression profile, identified on RNA sequencing, on an independent cohort of 99 T-ALL cases. We found high expression of MEF2C to be associated with prednisolone resistance (p=0.048) and CD34 expression (p=0.012). BAALC expression was associated with expression of CD34 (p=0.032) and myeloid markers (p=0.021). XIST and KDM6a expression levels were higher in females (p=0.047 and 0.011, respectively). Post-induction minimal residual disease (MRD) positivity was associated with high lncRNA PCAT18 (p=0.04), HHEX (p=0.027) and MEF2C (p=0.007). Early thymic precursor (ETP-ALL) immunophenotype was associated with high expression of MEF2C (p=0.003), BAALC (p=0.003), LYL1 (p=0.01), LYN (p=0.01), XIST (p=0.02) and low levels of ST20 (p=0.007) and EML4 (p=0.03). On survival analysis, MEF2C high expression emerged as significant predictor of 3-year event free survival (EFS) (low 71.78±6.58% vs high 36.57±10.74%, HR 3.5, p=0.0003) and overall survival (OS) (low 94.77±2.96% vs high 78.75±8.45%, HR 4.88, p=0.016) in our patients. LncRNA MALAT1 low expression also emerged as predictor inferior OS (low 76.02±10.48 vs high 94.11±3.31, HR 0.22, p=0.027).
Japan’s Covid mitigation strategy and its epidemic prediction
Authors: Tokuda Yasuharu , Kuniya Toshikazu
Published: May 2021

The COVID-19 epidemic curve in Japan was constructed based on daily reported data from January 14, 2020 until April 20, 2021. A SEIR compartmental model was used for the curve fitting by updating the estimation per wave. In the current vaccination pace of 1/1000, restrictions (state of emergency in Japan) would be repeated 4 times until the end of next March. In the case of 1/500, another round of restriction would be required in the summer 2021, after which the infection would be mitigated. In the case of 1/250, there would be no need for restriction after the current spring restriction. The scenario of completing the vaccination of 110 million people by the end of March 2020 corresponds to the case of 1/250 in this curve. When considering the likely spread of variant with greater infectiousness (here we assume 1.3 times greater than the original virus), 1/500 pace of vaccination would not be enough to contain it and need several series of restrictions. There are currently several variants of concern that are already spreading in urban areas in this country. In the new stage of the replacement of variants, if the vaccination pace could not be quadrupled from the current pace, Japan could not become a zero covid (zero corona) country at least one year.
Psychosis-like experiences and cognition in young adults: an observational and Mendelian randomisation study
Authors: Skirrow Caroline , Suddell Steph , Mahedy Liam , Penton-Voak Ian S. , Munafò Marcus R. , Wootton Robyn E.
Published: May 2021

Background

Psychosis-like experiences (PLEs) are common and associated with mental health problems and poorer cognitive function. There is limited longitudinal research examining associations between cognition and PLEs in early adulthood.

Aims

We investigated the association of PLEs with different domains of cognitive function, using cross-sectional and longitudinal observational, and Mendelian randomisation (MR) analyses.

Method

Participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed tasks of working memory at age 18 and 24, and tasks of response inhibition and facial emotion recognition at age 24. Semi-structured interviews at age 18 and 24 established presence of PLEs (none vs. suspected/definite). Cross-sectional and prospective regression analysis tested associations between PLEs and cognition (N=3,087 imputed sample). MR examined causal pathways between schizophrenia liability and cognition.

Results

The fully adjusted models indicated that PLEs were associated with poorer working memory performance (cross-sectional analyses: b=−0.18, 95% CI −0.27 to −0.08, p<0.001; prospective analyses: b=−0.18, 95% CI −0.31 to −0.06, p<0.01). A similar pattern of results was found for PLEs and response inhibition (cross-sectional analyses: b=7.29, 95% CI 0.96 to 13.62, p=0.02; prospective analyses: b=10.29, 95% CI 1.78 to 18.97, p=0.02). We did not find evidence to suggest an association between PLEs and facial emotion recognition. MR analyses were underpowered and did not support observational results.

Conclusions

In young adults, PLEs are associated with poorer concurrent and future working memory and response inhibition. Better powered genetically informed studies are needed to determine if these associations are causal.
Accurate prediction of protein torsion angles using evolutionary signatures and recurrent neural network
Authors: Xu Yong-Chang , ShangGuan Tian-Jun , Ding Xue-Ming , Cheung Ngaam J.
Published: May 2021

The amino acid sequence of a protein contains all the necessary information to specify its shape, which dictates its biological activities. However, it is challenging and expensive to experimentally determine the three-dimensional structure of proteins. The backbone torsion angles, as an important structural constraint, play a critical role in protein structure prediction, and accurately predicting the angles can considerably advance the tertiary structure prediction by accelerating efficient sampling of the large conformational space for low energy structures. On account of the rapid growth of protein databases and striking breakthroughs in deep learning algorithms, computational advances allow us to extract knowledge from large-scale data to address key biological questions. Here we propose evolutionary signatures that are computed from protein sequence profiles, and a deep neural network, termed ESIDEN, that adopts a straightforward architecture of recurrent neural networks with a small number of learnable parameters. The proposed ESIDEN is validated on three benchmark datasets, including D2020, TEST2016/2018, and CASPs datasets. On the D2020, using the combination of the four novel features and basic features, the ESIDEN achieves the mean absolute error (MAE) of 15.7 and 19.8 forϕandψ, respectively. Comparing to the best-so-far methods, we show that the ESIDEN significantly improves the angleψby the MAE decrements of more than 3.5 degrees on both TEST2016 and TEST2018 and achieves better MAE of the angleϕby decrements of at least 0.3 degrees although it adopts simple architecture and fewer learnable parameters. On fifty-nine template-free modeling targets, the ESIDEN achieves high accuracy by reducing the MAEs by 0.6 and more than 2.3 degrees on average for the torsion anglesϕandψin the CASPs, respectively. Using the predicted torsion angles, we infer the tertiary structures of four representative template-free modeling targets that achieve high precision with regard to the root-mean-square deviation and TM-score by comparing them to the native structures. The results demonstrate that the ESIDEN can make accurate predictions of the torsion angles by leveraging the evolutionary signatures. The proposed evolutionary signatures would be also used as alternative features in predicting residue-residue distance, protein structure, and protein-ligand binding sites. Moreover, the high-precision torsion angles predicted by the ESIDEN can be used to accurately infer protein tertiary structures, and the ESIDEN would potentially pave the way to improve protein structure prediction.
Discoidin Domain Receptor 2 regulates AT1R expression in Angiotensin II-stimulated cardiac fibroblasts via fibronectin-dependent Integrin-β1 signaling
Authors: Titus Allen Sam , Venugopal Harikrishnan , Ushakumary Mereena George , Wang Mingyi , Cowling Randy T. , Lakatta Edward G. , Kailasam Shivakumar
Published: May 2021

Recent reports on the cardioprotective effects of fibronectin inhibition following myocardial injury suggest a largely unexplored role for the extracellular matrix (ECM) glycoprotein in cardiac fibroblast function. We probed the molecular regulation and functional implications of fibronectin gene expression in cardiac fibroblasts exposed to Angiotensin II, a major pro-fibrotic factor in the myocardium. Using gene knockdown and over-expression approaches, western blotting and promoter pull-down assay, we show that collagen type I-activated Discoidin Domain Receptor 2 (DDR2) mediates Angiotensin II-stimulated transcriptional up-regulation of fibronectin by Yes-activated Protein in cardiac fibroblasts. Further, siRNA-mediated fibronectin knockdown attenuated Angiotensin II-stimulated expression of collagen type I and anti-apoptotic cIAP2, and enhanced susceptibility to apoptosis. Importantly, an obligate role for fibronectin was observed in Angiotensin II-stimulated expression of AT1R, the Angiotensin II receptor, which would link ECM signaling and Angiotensin II signaling in cardiac fibroblasts. Moreover, conditioned medium from DDR2- or fibronectin-silenced cardiac fibroblasts reduced AT1R expression in H9c2 cardiomyoblasts. The regulatory role of fibronectin in Angiotensin II-stimulated cIAP2, collagen type I and AT1R expression was mediated by Integrin-β1-integrin-linked kinase signaling. In vivo, we observed modestly reduced basal levels of AT1R in DDR2-null mouse myocardium, associated with the previously reported reduction in myocardial Integrin-β1 levels. The role of fibronectin, downstream of DDR2, could be a critical determinant of cardiac fibroblast-mediated wound healing following myocardial injury. In summary, our findings suggest a complex mechanism of regulation of cardiac fibroblast function involving two major extracellular matrix proteins, collagen type I and fibronectin, and their receptors, DDR2 and Integrin-β1.
Endothelial restoration of CAD GWAS gene PLPP3 by nanomedicine suppresses YAP/TAZ activity and reduces atherosclerosisin vivo
Authors: Zhu Jiayu , Yeh Chih-Fan , Huang Ru-Ting , Lee Tzu-Han , Shentu Tzu-Pin , Wu David , Yang Kai-Chien , Fang Yun
Published: May 2021

Genome-wide association studies (GWAS) have suggested new molecular mechanisms in vascular cells driving atherosclerotic diseases such as coronary artery disease (CAD) and ischemic stroke (IS). Nevertheless, a major challenge to develop new therapeutic approaches is to spatiotemporally manipulate these GWAS-identified genes in specific vascular tissuesin vivo. YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) have merged as critical transcriptional regulators in cells responding to biomechanical stimuli, such as in athero-susceptible endothelial cells activated by disturbed flow (DF). The molecular mechanisms by which DF activates while unidirectional flow (UF) inactivates YAP/TAZ remain incompletely understood. Recent studies demonstrated that DF and genetic predisposition (risk allele) of CAD/IS locus 1p32.2 converge to reduce phospholipid phosphatase 3 (PLPP3) expression in vascular endothelium. Restoration of endothelialPLPP3 in vivo, although remains challenging and unexplored, is hypothesized to reduce atherosclerosis. We devised a nanomedicine system integrating nanoparticles andCdh5promoter-driven plasmids to successfully restorePLPP3expression in activated endothelium, resulting in suppressed YAP/TAZ activity and reduced DF-induced atherosclerosis in mice. Mechanistically, our studies discovered a molecular paradigm by which CAD/IS GWAS genePLPP3inactivates YAP/TAZ by reducing lysophosphatidic acid (LPA)-induced myosin II and ROCK in endothelium under UF. These results highlight a new mechanistic link between GWAS and YAP/TAZ mechano-regulation and moreover, establish a proof of concept of vascular wall-based therapies employing targeted nanomedicine to manipulate CAD/IS GWAS genesin vivo.
3D Echo Planar Time-resolved Imaging (3D-EPTI) for ultrafast multi-parametric quantitative MRI
Authors: Wang Fuyixue , Dong Zijing , Reese Timothy G. , Rosen Bruce , Wald Lawrence L. , Setsompop Kawin
Published: May 2021

Multi-parametric quantitative MRI has shown great potential to improve the sensitivity and specificity of clinical diagnosis and to enhance our understanding of complex brain processes, but suffers from long scan time especially at high spatial resolution. To address this long-standing challenge, we introduce a novel approach, termed 3D Echo Planar Time-resolved Imaging (3D-EPTI), which significantly increases the acceleration capacity of MRI sampling, and provides high acquisition efficiency for multi-parametric MRI. This is achieved by exploiting the spatiotemporal correlation of MRI data at multiple timescales through new encoding strategies within and between efficient continuous readouts. Specifically, an optimized spatiotemporal CAIPI encoding within the readouts combined with a radial-block sampling strategy across the readouts enables an acceleration rate of 800 folds in thek-tspace. A subspace reconstruction was employed to resolve thousands of artifact-free high-quality multi-contrast images spaced at a time interval of ~1 ms. We have demonstrated the ability of 3D-EPTI to provide robust and repeatable whole-brain simultaneous T1, T2, T2*, PD and B1+mapping at high isotropic resolution within minutes (e.g., 1-mm isotropic resolution in 3 minutes), and to enable submillimeter multi-parametric imaging to study detailed brain structures.

Highlights

Ultra-fast acquisition for 3D multi-parametric quantitative MRI.

Simultaneous T1T2T2* PD and B1+mapping.

3-minute scan at 1-mm isotropic resolution with whole-brain coverage.

Multi-parametric mapping at 700-μm isotropic resolution in 10 minutes.

Repeatable quantification and cortical-depth analysis.
Virtual Recruitment is Here to Stay: 2020 ID Fellowship Program and Matched Applicant Recruitment Experiences
Authors: Rockney Danica , Benson Constance A. , Blackburn Brian G. , Chirch Lisa M. , Konold Victoria J. L. , Luther Vera P. , Razonable Raymund R. , Tackett Sean , Melia Michael T.
Published: May 2021

Background

Graduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Few data have been published regarding the consequences of this transition. We desired to understand (1) infectious diseases (ID) fellowship programs’ recruitment efforts and the effect of virtual recruitment on application and interview numbers, and (2) the number of programs to which matched applicants applied and interviewed, and their perspectives on virtual recruitment.

Methods

In 2020-21 we surveyed all United States ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach.

Results

PD response rate was 68/158 (43%); applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed. Applicants especially valued online program structure information, PD program overview videos, fellow testimonials, didactic and curriculum content, and current fellow profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want at least an option for virtual recruitment moving forward.

Conclusions

Virtual recruitment enabled programs to accommodate more applicants and highlighted applicants’ preferences for programs’ augmented online presences and time-limited interview days. Most programs and applicants want the option for virtual interviews.

Main Points

Virtual recruitment enables programs to accommodate more applicants. Applicants value programs’ augmented online presences and favor time-limited interview days. Most programs and applicants prefer in-person interviews and want at least an option for virtual interviews.