bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Development of Colonic Adenocarcinoma With Minimal Polyposis in a Young Child With Metastatic Hepatoblastoma and Germline APC Mutation
Authors: Liu Anthony P.Y. , Chung Patrick H.Y. , Au Yeung Rex K.H. , Chan Shing , Wong Kenneth K.Y. , Leung Suet-Yi , Chiang Alan K.S.
Published: May 2021

Germline adenomatous polyposis coli (APC) gene mutation is a cancer-predisposing condition commonly presenting as familial adenomatous polyposis. We describe a patient first diagnosed at the age of 3 years with metastatic hepatoblastoma. With a positive family history, germline testing confirmed maternally inherited APC mutation (p.Thr899Ansfs*13). The patient was subsequently diagnosed at 8 years with colonic adenocarcinoma in the absence of macroscopic polyposis. Total colectomy with adjuvant chemotherapy was delivered and the patient remained disease-free for 5 years since the second diagnosis. This report demonstrates the importance of considering germline APC mutation in children with hepatoblastoma, who may benefit from the early institution of colonoscopic surveillance.
Yoga and Bone Health
Authors: Fishman Loren M.
Published: May 2021

Osteoporosis is a public health problem affecting individuals globally. Yoga has been found to prevent and reverse bone loss. Yoga may result in better balance, improved posture, and greater range of motion, strength, and coordination, all factors that also mitigate the risk of falls and fractures. A 12-minute, 12-pose yoga regimen is discussed in detail. Once learned, the ongoing use of yoga is safe, without cost, and may be done lifelong.
Virtual reality-based physical therapy for patients with lower extremity injuries: feasibility and acceptability
Authors: Reilly Clifford A. , Greeley Aimee Burnett , Jevsevar David S. , Gitajn Ida Leah
Published: May 2021

Introduction:

Traditional physical therapy (PT) requires patients to attend weekly in-office supervised physical therapy appointments. However, between 50% and 70% of patients who would benefit do not receive prescribed PT due to barriers to access. Virtual Reality (VR) provides a platform for remote delivery of PT to address these access barriers.

Methods:

We developed a VR-PT program consisting of training, games, and a progress dashboard for 3 common lower extremity physical therapy exercises. We enrolled orthopaedic trauma patients with lower extremity injuries. Patients completed a VR-PT session, consisting of training and one of the exercise-based games. Pre- and post-VR-PT questionnaires were completed.

Results:

We enrolled 15 patients with an average age of 51 years. Fourteen patients said they would enroll in a randomized trial in which they had a 50% chance of receiving VR-PT vs receiving standard of care. When asked to rate their experience using the VR-PT module on a scale from 0-10—with 0 being anchored as “I hated it” and 10 being anchored as “I loved it”—the average rating was 7.5. Patients rated the acceptability of VR-PT as a 3.9 out of 5, the feasibility as a 4.0 out of 5, and the usability as a 67.5 out of 100.

Conclusion:

The response to VR-PT in this pilot study was positive overall. A VR-based PT program may add value for both patients and clinicians in terms of objective data collection (to aid in compliance monitoring, progression toward goals and exercise safety), increased engagement and increased access.
COVID-19 orthopaedic trauma volumes: a Canadian experience during lockdown and staged reopening
Authors: Ludwig Taryn E. , Samuel Tina L. , Vergouwen Martina , White Neil J.
Published: May 2021

Objectives:

The aim of this study is to report the impact of public health measures (PHM), including their relaxation, on surgical orthopaedic trauma volumes. We hypothesize an initial reduction in orthopaedic trauma volumes during lockdown followed by a surge as Stages 1 and 2 of reopening progressed in Summer 2020.

Methods:

All unscheduled surgical orthopaedic trauma cases from March through August were retrospectively reviewed in Calgary, Alberta, Canada, from 2008 to 2020. Trauma volumes from 2008 to 2019 were used to model expected 2020 volumes, and multivariable Poisson regression was used to determine the effect of PHM on orthopaedic trauma volumes.

Results:

A total of 22,331 trauma orthopaedic surgeries were included. During lockdown, there was a significant decrease in trauma volume compared with expected (−14.2%, −25.7 to −10.5%, P < .001) and there were significantly fewer ankle fractures (−17.8%, −30.9 to −2.2%, P = .027). During reopening Stage 2, there was a significant increase in trauma volume (+8.9%, +2.2 to +16.1%, P = .009). There was no change in the incidence of polytrauma, hip fracture, or wrist fracture during the pandemic.

Conclusions:

This study provides the first report of a surge in trauma volumes as PHM are relaxed during the COVID-19 pandemic. The ability to predict decreases in trauma volumes with strict PHM and subsequent surges with reopening can help inform operating room time management and staffing in future waves of COVID-19 or infectious disease pandemics.

Level of Evidence:

Prognostic – Level III
Airway Obstruction from a Tracheal Mass in a 5-Year-Old
Authors: Eitel Kelsey , Mitchell Ryan M. , Lefort Roxanna
Published: May 2021

Stridor is a common presenting symptom for children in emergency departments (EDs) and usually represents an infectious process, such as croup, or aspiration of a foreign body. We present the case of an otherwise healthy 5-year-old girl with episodic increased work of breathing for several months that was initially diagnosed as asthma by her primary care physician. She subsequently presented to the ED with acutely worsening noisy breathing and dyspnea. Patient and parent denied any recent foreign body ingestions or choking episodes. We gave multiple doses of racemic epinephrine in the ED without symptom improvement. A lateral neck x-ray showed an occlusive subglottic airway mass. Otolaryngology (ENT) evaluation demonstrated an 85% airway occlusion. The mass was partially resected, resolving all of her respiratory symptoms. Although primary airway tumors in children are rare, they must be considered on the differential diagnosis of new noisy breathing or respiratory distress. Failure to diagnose these tumors in a timely manner can be life-threatening.
The 10-Year Experience with Volume Distribution Mastopexy: A Novel, Safe, and Efficient Method for Breast Rejuvenation
Authors: Hamdi Moustapha , Chahine Fadl , Alharami Sara , De Baerdemaeker Randy , Hendrickx Benoit , Zeltzer Assaf
Published: May 2021

Background:

Recurrent ptosis may occur after mastopexy procedures over time. The volume distribution mastopexy technique provides breast lifting with projection enhancement and maintains breast suspension.

Method:

Since 2010, 50 patients underwent volume distribution mastopexy procedures. The technique consists of a superior or superomedial pedicle, dissection of a Würinger-septum–based chest wall flap, suspension of the flap to the pectoralis major muscle using a prosthetic mesh, gland suture to the mesh, and fat grafting if required. A prospective study was conducted. Nipple position and length of the lower pole distance of the breast were noted. Patient satisfaction and results evaluation were reported using a Likert scale.

Results:

A Vicryl mesh was used in the first 23 patients and a mixed polyester/Vicryl mesh was used in the following 27 patients. Wound dehiscence occurred in one patient. At an average follow-up of 3 years, nipple position remained stable in position, but lower pole distance elongation was observed in five patients (20 percent) and in one patient (3 percent) who had Vicryl mesh and mixed mesh respectively (p < 0.05). Only four breasts (4.7 percent) demonstrated significant lower pole elongation over time (>15 percent), all in the Vicryl mesh group. Worth noting, both the patients and the independent evaluators provided high ratings of the result of 4.7 and 4.6, respectively, on a Likert scale.

Conclusions:

The volume distribution mastopexy technique repositions the ptotic gland with a mesh to suspend the breast gland and to maintain the lifting effect. However, the synthetic mixed mesh proved to be significantly more effective in achieving this goal.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Practice Diversity and Burn Center Growth
Authors: Lineaweaver William C. , Mullins R. Fred
Published: May 2021

Background

Growth and sustainability of burn practices can be impaired by irregular patterns of patient presentations, resulting in uneven utilization of facilities and staff. Burn care itself may not engage the full capacities of members of burn care teams. To address these problems, we organized a burn and reconstruction center to provide statewide acute care as Mississippi's only burn unit, to fully integrate reconstructive surgery into management of burn patients, and to diversify practice based on plastic surgery scope of practice. The first 10 years of this unit were reviewed to evaluate the performance of this scheme.

Methods

Burn admissions to and surgical procedures at this unit between July 2009 and June 2019 were analyzed to quantify acute burn care, secondary reconstructive burn care, and categories of practice growth.

Results

The unit admitted 5469 acute burn patients with a mortality rate of 1.49%. Comparing year 10 to year 1 of practice, acute burn admissions increased 58%. Total operations increased 276%. Acute burn procedures increased 176%. Secondary burn procedures increased 405%. Nonburn procedures increased 352%, with the subset of nonburn hand surgery increasing 1062%.

Conclusion

Acute burn admissions and procedures increased over this period, but greater growth was seen in secondary burn procedures and nonburn procedures, especially hand cases. Expansion of practice into areas within the overall skill sets of burn team members was an effective growth strategy.
Involuntary “Voluntary” Nystagmus
Authors: Rosenberg Michael L.
Published: May 2021

Background:

Voluntary nystagmus is a common phenomenon in the general population and is believed to be under voluntary control. Some patients have an eye movement disorder indistinguishable from voluntary nystagmus and yet have no control over these movements.

Methods:

Four patients with involuntary eye movements consisting of spontaneous or induced bursts of saccadic eye movements with no intersaccadic interval are described. All eye movements were typical of “voluntary nystagmus,” yet they denied any control over the movements. In none of the patients was there any evidence of psychopathology or secondary gain.

Results:

Two types of patients with involuntary eye movements that were indistinguishable from voluntary nystagmus are presented. One group of 2 patients had clear neurological disease, whereas another 2 had no evidence of any neurological pathology.

Conclusions:

The patterns seen in these patients suggest that there is a spectrum of oculomotor saccadic instabilities that includes voluntary nystagmus on one extreme and ocular flutter on the other. In between these 2 are both normal and abnormal patients with eye movements indistinguishable from ocular flutter/voluntary nystagmus that may or may not be induced by convergence. It is suggested that involuntary “voluntary nystagmus” is a real condition and that psychopathology should be ruled in rather than simply assumed.
Mild Bilateral Internuclear Ophthalmoplegia: The Diagnostic Role of the Vertical Posterior Canal Vestibulo-Ocular Reflex in Acute Brainstem Demyelination, a Clinical–Radiologic Correlation
Authors: Manrique Luis G. , Zhang Xiajoun , Kathryn Laurel , Marie Catherine , Kattah Jorge C.
Published: May 2021

Background:

The ocular signs of internuclear ophthalmoplegia (INO) with slow, restricted adduction of one eye and abduction nystagmus of the contralateral eye are easily recognized and have a high localizing/lateralizing value. However, subtle INO is difficult to diagnose. Recent reports identified novel vestibular abnormalities in unilateral and bilateral INO. Frequent findings include decreased horizontal and posterior canal gains, and generally relative sparing of both anterior canals. We studied one patient with a subtle bilateral INO, performed serial quantitative saccade (QS) and video head impulse test (vHIT), and correlated clinical–radiological findings caused by acute demyelination.

Methods:

Single case study of a 30-year-old man presented with 1 week of painless, binocular, horizontal diplopia in left gaze. We performed 3 serial neurological examination, QS, vHIT, and clinical–MRI correlation (1 pretreatment and 2 post steroid treatment).

Results:

We found bilateral slow adducting, clinically positive posterior canal HITs, and borderline abducting saccade velocity, without abducting nystagmus. The videonystagmography with fixation block showed bilateral horizontal gaze evoked nystagmus, and vHIT testing confirmed decreased right horizontal and bilateral posterior canal gains. The abnormalities resolved after steroid treatment. MRI showed acute bilateral medial longitudinal fascicle demyelinating lesions.

Conclusions:

A bilaterally positive, posterior, canal HIT and slow adduction saccades are localizing findings in bilateral INO, even in the absence of abduction nystagmus. Quantitative confirmation of these findings suggest most frequently an ischemic or demyelinating disorder and are a compelling indication for MRI. This case shows value to testing multiaxial head impulses and performing QS and vHIT in brainstem lesions.
Vitreoretinal Findings in Nonarteritic Ischemic Optic Neuropathy
Authors: Molaie Amir M. , Pramil Varsha , Hedges Thomas R. , Tomb Landon C. , Vuong Laurel N.
Published: May 2021

Background:

Although nonarteritic anterior ischemic optic neuropathy (NAION) is considered a disorder that primarily affects the optic nerve head, optical coherence tomography (OCT) shows peripapillary and foveal subretinal fluid associated with optic disc swelling from NAION. We sought to further evaluate retinal and vitreous changes in patients with NAION.

Methods:

Patients diagnosed with NAION at the New England Eye Center between 2013 and 2017 were evaluated using OCT. The presence and distribution of subretinal fluid was analyzed. Evidence of other vitreoretinal changes, including vitreopapillary traction (VPT) and the presence of hyperreflective dots (HRD), were also determined.

Results:

Twenty-five eyes from 20 patients who presented within 4 weeks of symptom onset were assessed. Peripapillary subretinal fluid was seen in 16 eyes (64%). Of those eyes, the subretinal fluid extended into the macula in 4 eyes (16%). Visual acuity improved in 2 of 4 eyes after subfoveal fluid resolution. Intraretinal cysts located in the peripapillary region were seen in 8 eyes (32%), HRD were noted in 11 (44.0%). There was no evidence of VPT.

Conclusions:

A substantial number of patients with NAION have subretinal fluid on OCT, consistent with prior reports. Resolution of subfoveal fluid may result in some recovery of visual acuity. Other retinal changes, such as intraretinal cysts and HRD, are present but have unclear implications. We did not find evidence of a primary role of VPT in the pathophysiology of NAION.
Binocular Visual Field and Vision-Related Quality of Life in Patients With Hemianopia
Authors: Burgos-Blasco Barbara , Perez-Garcia Pilar , Fernandez-Vigo Jose I. , Benito-Pascual Blanca , Hernandez-Garcia Elena , Saenz-Frances Federico , Santos-Bueso Enrique
Published: May 2021

Background:

Hemianopias can have a severe impact on functional ability and quality of life (QoL). Binocular visual field (VF) analysis is clinically more relevant to visual function than monocular VF. The aim is to analyze the binocular VF of patients with hemianopias and its association with the monocular VF and to assess the QoL of these patients through questionnaires specifically related to vision compared with healthy controls.

Methods:

The case–control study included patients with hemianopias and controls. Sex, age, general history, etiology, location of the lesion, and time since the lesion appeared were recorded. Monocular VF and Esterman binocular VF were performed. VF defect, mean defect (MD), and Esterman scores were recorded. Visual Activities Questionnaire (VAQ-33) and Visual Function Questionnaire (VFQ-25) questionnaires were administered.

Results:

Twenty patients with hemianopia and 22 healthy controls were included. The Esterman score in homonymous hemianopia patients (n = 17) correlated with best eye MD (r = −0.62, P = 0.01), worst eye MD (r = −0.70, P = 0.002), and average MD (r = −0.68, P = 0.003). Compared with healthy control subjects, patients with homonymous hemianopia had significantly lower VFQ-25 score and in 10/12 subscales (all P < 0.001). VAQ-33 scores revealed lower overall and subscales scores with the exception of light/dark adaptation (P = 0.08). Correlations were found between monocular and binocular VF scores and general vision (r = −0.55), peripheral vision (on both questionnaires, r-range −0.75 to 0.47), VFQ-25 and VAQ-33 overall scores (r = −0.59, −0.49 and 0.50), and glare disability (r = 0.53 and 0.67).

Conclusions:

Hemianopic VF defects involve a major alteration in the patients' vision-related QoL.
Who complies with coronavirus disease 2019 precautions and who does not?
Authors: Urbán Róbert , Király Orsolya , Demetrovics Zsolt
Published: May 2021

Purpose of review

Severe acute respiratory syndrome (SARS)–coronavirus disease 2019 (COVID-19) virus imposes a higher risk of complications and mortality among people with mental disorders. Until widely available vaccines, adherence to preventive behaviours remains the most crucial tool to prevent SARS/COVID-19 virus transmission. Our review focuses on the determinants of adherence behaviours.

Recent findings

Adherence behaviours include the use of a face mask and protective gloves, personal hygienic behaviours (handwashing or using hand sanitiser), and keeping physical distance and avoiding social gatherings. In almost all studies, males and younger people show less adherence. Risk perception and health beliefs (especially perceived severity of COVID-19 related conditions) can explain the sex and age differences in adherence. Studies covering the impact of mental disorders on adherence are surprisingly missing, with the exception of smoking.

Engaging men and young people in adopting preventive behaviours is crucial in protecting the whole community and specific vulnerable populations. There is a lack of studies investigating preventive behaviours among people living with mental disorders and addiction problems. Furthermore, descriptive and intervention studies are needed to understand and improve the adherence of this population to preventive behaviours.
'Candidatus Phytoplasma dypsidis', a novel taxon associated with a lethal wilt disease of palms in Australia
Authors: Jones Lynne M. , Pease Bradley , Perkins Sandy L. , Constable Fiona E. , Kinoti Wycliff M. , Warmington David , Allgood Ben , Powell Sonya , Taylor Pieter , Pearce Ceri , Davis Richard I.
Published: May 2021

A phytoplasma was initially detected in Dypsis poivriana by nested and real-time PCR from the botanical gardens in Cairns, Queensland, Australia in 2017. Further surveys in the Cairns region identified phytoplasma infections in eight additional dying ornamental palm species (Euterpe precatoria, Cocos nucifera, Verschaffeltia splendida, Brassiophoenix drymophloeodes, Burretiokentia hapala, Cyrtostachys renda, Reinhardtia gracilis, Carpoxylon macrospermum), a Phoenix species, a Euterpe species and two native palms (Archontophoenix alexandrae). Analysis of 16S rRNA gene sequences showed that this phytoplasma is distinct as it shared less than 97.5 % similarity with all other ‘Candidatus Phytoplasma’ species. At 96.3 % similarity, the most closely related formally described member of the provisional 'Ca. Phytoplasma' genus was 'Ca. Phytoplasma noviguineense', a novel taxon from the island of New Guinea found in monocotyledonous plants. It was slightly more closely related (96.6–96.8 %) to four palm-infecting strains from the Americas, which belong to strain group 16SrIV and which have not been assigned to a formal 'Candidatus Phytoplasma’ species taxon. Phylogenetic analysis of the 16S rRNA gene and ribosomal protein genes of the phytoplasma isolate from a dying coconut palm revealed that the phytoplasma represented a distinct lineage within the phytoplasma clade. As the nucleotide identity with other phytoplasmas is less than 97.5 % and the phylogenetic analyses show that it is distinct, a novel taxon 'Candidatus Phytoplasma dypsidis' is proposed for the phytoplasma found in Australia. Strain RID7692 (GenBank accession no. MT536195) is the reference strain. The impact and preliminary aspects of the epidemiology of the disease outbreak associated with this novel taxon are described.
Cas9-targeted nanopore sequencing reveals epigenetic heterogeneity after de novo assembly of native full-length hepatitis B virus genomes
Authors: Goldsmith Chloe , Cohen Damien , Dubois Anaëlle , Martinez Maria Guadalupe , Petitjean Kilian , Corlu Anne , Testoni Barbara , Hernandez-Vargas Hector , Chemin Isabelle
Published: May 2021

Hepatitis B virus (HBV) contains a 3.2 kb DNA genome and causes acute and chronic hepatitis. HBV infection is a global health problem, with 350 million chronically infected people at increased risk of developing liver disease and hepatocellular carcinoma (HCC). Methylation of HBV DNA in a CpG context (5mCpG) can alter the expression patterns of viral genes related to infection and cellular transformation. Moreover, it may also provide clues as to why certain infections are cleared or persist with or without progression to cancer. The detection of 5mCpG often requires techniques that damage DNA or introduce bias through a myriad of limitations. Therefore, we developed a method for the detection of 5mCpG on the HBV genome that does not rely on bisulfite conversion or PCR. With Cas9-guided RNPs to specifically target the HBV genome, we enriched in HBV DNA from primary human hepatocytes (PHHs) infected with different HBV genotypes, as well as enriching in HBV from infected patient liver tissue, followed by sequencing with Oxford Nanopore Technologies MinION. Detection of 5mCpG by nanopore sequencing was benchmarked with bisulfite-quantitative methyl-specific qPCR (BS-qMSP). The 5mCpG levels in HBV determined by BS-qMSP and nanopore sequencing were highly correlated. Our nanopore sequencing approach achieved a coverage of ~2000× of HBV depending on infection efficiency, sufficient coverage to perform a de novo assembly and detect small fluctuations in HBV methylation, providing the first de novo assembly of native HBV DNA, as well as the first landscape of 5mCpG from native HBV sequences. Moreover, by capturing entire HBV genomes, we explored the epigenetic heterogeneity of HBV in infected patients and identified four epigenetically distinct clusters based on methylation profiles. This method is a novel approach that enables the enrichment of viral DNA in a mixture of nucleic acid material from different species and will serve as a valuable tool for infectious disease monitoring.
Central inhibition of pain is augmented in women with self-injurious behavior
Authors: Lalouni Maria , Fust Jens , Bjureberg Johan , Kastrati Granit , Fondberg Robin , Fransson Peter , Jayaram-Lindström Nitya , Kosek Eva , Hellner Clara , Jensen Karin B.
Published: May 2021

Individuals who engage in nonsuicidal self-injury (NSSI) have demonstrated higher pain thresholds and tolerance compared with individuals without NSSI. The objective of the study was to assess which aspects of the pain regulatory system that account for this augmented pain perception. In a cross-sectional design, 81 women, aged 18-35 (mean [SD] age, 23.4 [3.9]), were included (41 with NSSI and 40 healthy controls). A quantitative sensory testing protocol, including heat pain thresholds, heat pain tolerance, pressure pain thresholds, conditioned pain modulation (assessing central down-regulation of pain), and temporal summation (assessing facilitation of pain signals) was used. Thermal pain stimuli were assessed during fMRI scanning and NSSI behaviors and clinical symptoms were self-assessed. NSSI participants demonstrated higher pain thresholds during heat and pressure pain compared to controls. During conditioned pain modulation, NSSI participants showed a more effective central down-regulation of pain for NSSI participants. Temporal summation did not differ between the groups. There were no correlations between pain outcomes and NSSI behaviors or clinical characteristics. The fMRI analyses revealed increased activity in the primary and secondary somatosensory cortex in NSSI participants, compared to healthy controls, which are brain regions implicated in sensory aspects of pain processing. The findings suggest segregated inhibitory mechanisms for pain and emotion in NSSI, as pain insensitivity was linked to enhanced inhibitory control of pain in spite of significant impairments in emotion regulation. This may represent an endophenotype associated with a greater risk for developing self-injurious behavior.
Transferability and interpretability of the sepsis prediction models in the intensive care unit
Authors: Chen Qiyu , Li Ranran , Lin ChihChe , Lai Chiming , Chen Dechang , Qu Hongping , Huang Yaling , Lu Wenlian , Tang Yaoqing , Li Lei
Published: May 2021

Objective

We aimed to develop an early warning system for real-time sepsis prediction in the ICU by equipping with interpretation analysis and transfer learning tools to improve the feasibility to deploy the sepsis prediction system, particularly to target cohorts.

Design

Retrospective and observational study.

Setting

Medical Information Mart for Intensive Care (MIMIC) dataset, the private Historical Database of local Ruijin Hospital (HDRJH), and data collected from Ruijin real-world study.

Patients

6891 patients from MIMIC dataset and 453 patients from HDRJH for model development and 67 cases from Ruijin real-world data for model evaluation.

Interventions

None.

Measurements and Main Results

Light Gradient Boosting Machine (LightGBM) and multilayer perceptron (MLP) were trained on MIMIC dataset and then finetuned on HDRJH using transfer learning technique. Ultimately, the performance of the sepsis prediction system was further evaluated in the real-world study in the ICU of the target Ruijin Hospital. The area under the receiver operating characteristic curves (AUCs) for LightGBM and MLP models derived from MIMIC were 0.98–0.98 and 0.95–0.96 respectively on MIMIC dataset, and, in comparison, 0.82–0.86 and 0.84–0.87 respectively on HDRJH, from 1–5h preceding. After transfer learning and ensemble learning, the AUCs of the final ensemble model were enhanced to 0.94–0.94 on HDRJH and to 0.86–0.9 in the real-world study in the ICU of the target Ruijin Hospital. In addition, the Shapley additive explanation (SHAP) analysis illustrated the importance of age, antibiotics, net balance, and ventilation for sepsis prediction, making the model interpretable.

Conclusions

Our machine learning model allows accurate real-time prediction of sepsis within 5-h preceding. Transfer learning can effectively improve the feasibility to deploy the prediction model in the target cohort, effectively ameliorating the model performance for external validation. SHAP analysis may illuminate the importance of optimizing antibiotic use and restricting fluid management.

Trial registration

NCT05088850 (retrospectively registered).

Key Points

Question

We aimed to develop an early warning system for real-time sepsis prediction in the ICU and to improve the feasibility to deploy the system to target cohorts.

Findings

Transfer learning technique effectively enhanced the AUCs for LightGBM and MLP models on the target cohort, HDRJH, from 0.82–0.86 and 0.84–0.87 to 0.93-0.94 and 0.92-0.93 for 1-5 hour preceding. Additionally, SHAP analysis illuminated the importance of optimizing antibiotic use and restricting fluid management.

Meaning

Transfer learning can improve the feasibility to deploy the prediction model to the target cohort, and SHAP analysis made the prediction model interpretable.
Drug Repositioning by Merging Active Subnetworks Validated in Cancer and COVID-19
Authors: Lucchetta M. , Pellegrini M.
Published: May 2021

Computational Drug Repositioning aims at ranking and selecting existing drugs for use in novel diseases or existing diseases for which these drugs were not originally designed. Using vast amounts of available omic data in digital form within anin silicoscreening has the potential for speeding up considerably the shortlisting of promising candidates in response to outbreaks of diseases such as COVID-19 for which no satisfactory cure has yet been found. We describe DrugMerge as a methodology for preclinical computational drug repositioning based on merging multiple drug rankings obtained with an ensemble of Disease Active Subnetwork construction algorithms. DrugMerge uses differential transcriptomic data from cell lines/tissues of patients affected by the disease and differential transcriptomic data from drug perturbation assays, in the context of a large gene co-expression network. Experiments with four benchmark diseases (Asthma, Rheumatoid Arthritis, Prostate Cancer, and Colorectal Cancer) demonstrate that our method detects in first position drugs in clinical use for the specified disease, in all four cases. Our method is competitive with the state-of-the-art tools such as CMAP (Connectivity Map). Application of DrugMerge to COVID-19 data found rankings with many drugs currently in clinical trials for COVID-19 in top positions, thus showing that DrugMerge is able to mimic human expert judgment.
Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection
Authors: Devadoss Dinesh , Acharya Arpan , Manevski Marko , Pandey Kabita , Borchert Glen M. , Nair Madhavan , Mirsaeidi Mehdi , Byrareddy Siddappa N. , Chand Hitendra S.
Published: May 2021

Respiratory epithelial cells are the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the 3D human airway tissue model to evaluate innate epithelial cell responses to SARS-CoV-2 infection. A SARS-CoV-2 clinical isolate productively infected the 3D-airway model with a time-dependent increase in viral load (VL) and concurrent upregulation of airway immunomodulatory factors (IL-6, ICAM-1, andSCGB1A1) and respiratory mucins (MUC5AC, MUC5B, MUC2, andMUC4), and differential modulation of select long noncoding RNAs (lncRNAs i.e.,LASI, TOSL, NEAT1, andMALAT1). Next, we examined these immunomodulators in the COVID-19 patient nasopharyngeal swab samples collected from subjects with high- or low-VLs (∼100-fold difference). As compared to low-VL, high-VL patients had prominent mucoinflammatory signature with elevated expression ofIL-6, ICAM-1, SCGB1A1, SPDEF, MUC5AC, MUC5B, andMUC4. Interestingly,LASI, TOSL, andNEAT1lncRNA expressions were also markedly elevated in high-VL patients with no change inMALAT1expression. In addition, dual-staining ofLASIand SARS-CoV-2 nucleocapsidN1RNA showed predominantly nuclear/perinuclear localization at 24 hpi in 3D-airway model as well as in high-VL COVID-19 patient nasopharyngeal cells, which exhibited high MUC5AC immunopositivity. Collectively, these findings suggest SARS-CoV-2 induced lncRNAs may play a role in acute mucoinflammatory response observed in symptomatic COVID-19 patients.
A Time Series Analysis and Predictive Modeling of COVID-19 Impacts in the African American Community
Authors: Oladunni Timothy , Tossou Sourou , Denis Max , Ososanya Esther , Adesina Joseph
Published: May 2021

Background

Sometimes in 2019, there was an outbreak of coronavirus pandemic. Data shows that the virus has infected millions of people and claimed thousands of lives. Vaccination and other non-pharmacological interventions have brought a relief; however, COVID-19 left some indelible marks. This work focuses on a time series analysis and prediction of COVID-19 fatality rates in the Black community. Decision makers will find the work useful in building a robust architecture for a resilient pandemic preparedness and responsiveness against the next pandemic. Method: Our analysis of COVID-19 cases and deaths spans March 2020 to December 2020. Assuming there was no vaccine and other factors remained the same, we hypothesized that COVID-19 disproportionality would have continued. To test our hypothesis, COVID-19 forecasting cases and deaths models were built for the total population as well as the Black population. Holt and Holt-Winters exponential smoothing forecast methodologies were used for the forecast modeling. Forecasting accuracy was based on Mean Absolute Percentage Error (MAPE). Furthermore, we designed, developed, and evaluated a fatality rate predictive model for a Black county. Considering the number of ethnic groups in the USA, a Black county was defined as any county in the USA that at least 45% of its population are Blacks. Five learning algorithms were trained and evaluated. Dataset was a merger of datasets obtained from John Hopkins COVID-19 repository, US Census Bureau and US Center for Disease Control and Prevention.

Results and Conclusion

Time series analysis shows that there exists a strong evidence of COVID-19 disproportionate impacts in the states investigated. Using 9 different criteria for performance comparison, our predictive modeling showed that decision tree model has a slight edge over other models. Our experiment suggests that Blacks and senior citizens with pre-existing condition living in Georgia State are the most vulnerable to COVID-19.
NEOage clocks - Epigenetic clocks to estimate post-menstrual and postnatal age in preterm infants
Authors: Graw Stefan , Camerota Marie , Carter Brian S. , Helderman Jennifer , Hofheimer Julie A. , McGowan Elisabeth C. , Neal Charles R. , Pastyrnak Steven L. , Smith Lynne M. , DellaGrotta Sheri A. , Dansereau Lynne M. , Padbury James F. , O’Shea T. Michael , Lester Barry M. , Marsit Carmen J. , Everson Todd M.
Published: May 2021

Epigenetic clocks based on DNA methylation (DNAm) can to accurately predict chronological age and are thought to capture biological aging. A variety of epigenetic clocks have been developed for different tissue types and age ranges, but none has focused on age prediction for preterm infants. Epigenetic estimators of biological age might be especially informative in epidemiologic studies of neonates, particularly those born preterm, since this is a key developmental window. Neonatal DNAm is dynamic and preterm infants are at heightened risk of developmental impairments. We aimed to fill this gap by developing epigenetic clocks for neonatal aging in preterm infants.

As part of the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, buccal cells were collected at NICU discharge to profile DNAm levels in 542 very preterm infants. We applied elastic net regression to identify four epigenetic clocks (NEOage) predictive of post-menstrual and postnatal age, compatible with the Illumina EPIC and 450K arrays. We observed high correlations between predicted and reported ages (0.93 – 0.94) with root mean squared errors (1.28 - 1.63 weeks).

Epigenetic estimators of neonatal aging in preterm infants can be useful tools to evaluate biological maturity and associations with neonatal and long-term morbidities.
The bidirectional causal effects of brain morphology across the life course and risk of Alzheimers disease: A cross-cohort comparison and Mendelian randomization meta-analysis
Authors: Korologou-Linden Roxanna , Xu Bing , Coulthard Elizabeth , Walton Esther , Wearn Alfie , Hemani Gibran , White Tonya J.H , Cecil Charlotte A.M , Sharp Tamsin , Tiemeier Henning , Banaschewski Tobias , Bokde Arun , Quinlan Erin , Desrivieres Sylvane , Flor Herta , Grigis Antoine , Gowland Penny , Heinz Andreas , Bruhl Rudiger , Martinot Jean-Luc , Paillere Martinot Marie-Laure , Artiges Eric , Nees Frauke , Papadopoulos Orfanos Dimitris , Paus Tomas , Poustka Luise , Sabina Millenet , Frohner Juliane , Robinson Lauren , Smolka Michael , Walter Henrik , Winterer Jeanne , Whelan Robert , Schumann Gunter , Howe Laura D , Ben-Shlomo Yoav , Davies Neil M , Anderson Emma L
Published: May 2021

Neuropathological changes associated with Alzheimers disease (AD) can occur decades before clinical symptoms. We investigated whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or accelerating brain atrophy, respectively. We used bidirectional two-sample Mendelian randomization to estimate the effects of genetic liability to AD on global and regional cortical thickness, total intracranial volume, volume of subcortical structures and cerebral white matter in 36,842 participants aged eight to 81 years across five independent cohorts, and the effects of global and regional cortical thickness and subcortical volumes on AD risk in 94,337 participants. Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. We also found little evidence to suggest brain morphology alters AD risk. Thus, genetic liability to AD is likely to alter mechanisms and/or rates of neurodegeneration, rather than reduce structural brain reserve.
Association of dietary patterns and body phenotypes in Brazilian adolescents
Authors: Rinaldi Ana Elisa Madalena , Conde Wolney Lisboa , Enes Carla Cristina
Published: May 2021

Objective

To investigate the association between dietary patterns and physical activity and body phenotypes in Brazilian adolescents.

Methods

Cross-sectional study using data from a school-based study with 1,022 Brazilian adolescents aged 10 to 19 years. Body phenotypes (BP) and dietary patterns (DP) were defined using principal components analysis. BP was defined using anthropometric, body composition, biochemical, and sexual maturation, and DP from 19 food groups categorized from a food frequency questionnaire containing 58 food items. We performed a scatter plot to describe the relationship between energy expenditure assessed by MET and BP scores. The association between DP and BP, adjusted by sex, age and socioeconomic status, was assessed by linear regression model.

Results

We identified five BP (BP1adiposity, BP2puberty, BP3biochemical, BP4muscular, BP5lipids_biochemical) and five DP (DP1ultraprocessed_foods, DP2fresh_foods, DP3bread_rice_beans, DP4culinary_preparation, DP5cakes_rice_beans). There are higher scores of BP_adiposity for obese adolescents, but energy expenditure was similar for obese and non-obese. Physical activity was positively associated with body mass index, BP_adiposity and BP_puberty. We observed negative association between DP_ultraprocessed and BMI, and a positive between DP_fresh_foods. DP_fresh_foods was positively associated with BP_adiposity; DP_ultraprocessed and DP_culinary_preparation were negatively associated with this BP. BP_biochemical was negatively associated with DP_fresh_foods.

Conclusion

We identified negative association between DP mainly composed by ultraprocessed foods and fresh foods and BPadiposity. These associations need to be more explored, especially in adolescents, because both DP and BP were defined using multivariate analysis.
Effectiveness of BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on mortality following COVID-19
Authors: Bernal Jamie Lopez , Andrews Nick , Gower Charlotte , Stowe Julia , Tessier Elise , Simmons Ruth , Ramsay Mary
Published: May 2021

We estimated risk of death in vaccinated compared to unvaccinated COVID-19 cases. Cases vaccinated with 1 dose of BNT162b2 had 44% reduced risk of death, 55% with 1 dose of ChAdOx1, and 69% with 2 doses of BNT162b2. This is on top of the protection provided against becoming a case.
Telemedicine For Prenatal Care: A Systematic Review
Authors: Nguyen Eliza , Engle Grace , Subramanian Shalini , Fryer Kimberly
Published: May 2021

Objective

To evaluate the effectiveness of telehealth-enhanced prenatal care.

Data Sources

We searched for primary literature in PubMed, EMBASE, and Cochrane Library databases.

Methods of Study Selection

Studies were included if they were written in English and used telehealth as an adjunct to or substitute for elements of a comprehensive prenatal care system, with pregnant women as the study population. Studies were excluded if they did not involve comprehensive prenatal care, were not in English, or were abstracts only. Two reviewers independently screened studies by titles, abstracts, and full text. Conflicts were resolved by a third reviewer. Remaining conflicts were resolved by a fourth reviewer. Risk of bias was performed independently by two reviewers. Conflicts were resolved by a third reviewer.

Tabulation, Integration and Results

The initial search identified 2707 studies, of which 7 met inclusion criteria. One additional study was identified in the grey literature. Studies included 4 non-randomized controlled studies, 1 randomized controlled trial, 2 qualitative studies, and 1 active clinical trial. Telehealth-enhanced prenatal care included remote monitoring and/or virtual visits. Interventions reduced the number of in-person appointments. Patients and providers had high rates of satisfaction with prenatal care delivered via telehealth. Pregnancy outcomes were similar between the intervention and control groups with the exception of one study identifying higher rates of pre-eclampsia and another showing higher rates of gestational diabetes in the telehealth group. Risk of bias assessment revealed moderate bias in all of the non-randomized studies. The randomized controlled trial had low risk of bias.

Conclusion

Telemedicine-enhanced prenatal care may decrease the number of in-person prenatal care visits and increase access to care. Future studies should be done to determine neonatal and maternal outcomes of remote care and to study effectiveness of these interventions for women of color and low socioeconomic status.
Rapid incidence estimation from SARS-CoV-2 genomes reveals decreased case detection in Europe during summer 2020
Authors: Smith Maureen Rebecca , Trofimova Maria , Weber Ariane , Duport Yannick , Kühnert Denise , von Kleist Max
Published: May 2021

In May 2021, over 160 million SARS-CoV-2 infections have been reported worldwide. Yet, the true amount of infections is unknown and believed to exceed the reported numbers by several fold, depending on national testing policies that can strongly affect the proportion of undetected cases. To overcome this testing bias and better assess SARS-CoV-2 transmission dynamics, we propose a genome-based computational pipeline, GInPipe, to reconstruct the SARS-CoV-2 incidence dynamics through time. After validating GInPipe against in silico generated outbreak data, as well as more complex phylodynamic analyses, we use the pipeline to reconstruct incidence histories in Denmark, Scotland, Switzerland, and Victoria (Australia) solely from viral sequence data.

The proposed method robustly reconstructs the different pandemic waves in the investigated countries and regions, does not require phylodynamic reconstruction, and can be directly applied to publicly deposited SARS-CoV-2 sequencing data sets. We observe differences in the relative magnitude of reconstructed versus reported incidences during times with sparse availability of diagnostic tests. Using the reconstructed incidence dynamics, we assess how testing policies may have affected the probability to diagnose and report infected individuals. We find that under-reporting was highest in mid 2020 in all analysed countries, coinciding with liberal testing policies at times of low test capacities.

Due to the increased use of real-time sequencing, it is envisaged that GInPipe can complement established surveillance tools to monitor the SARS-CoV-2 pandemic and evaluate testing policies. The method executes within minutes on very large data sets and is freely available as a fully automated pipeline from https://github.com/KleistLab/GInPipe.
The specter of Manaus: the risks of a rapid return to pre-pandemic conditions after COVID-19 vaccine rollout
Authors: Van Egeren Debra , Stoddard Madison , Novokhodko Alexander , Rogers Michael , Joseph-McCarthy Diane , Zetter Bruce , Chakravarty Arijit
Published: May 2021

The development and deployment of several SARS-CoV-2 vaccines in a little over a year is an unprecedented achievement of modern medicine. The high levels of efficacy against transmission for some of these vaccines makes it feasible to use them to suppress SARS-CoV-2 altogether in regions with high vaccine acceptance. However, viral variants with reduced susceptibility to vaccinal and natural immunity threaten the utility of vaccines, particularly in scenarios where a return to pre-pandemic conditions occurs before the suppression of SARS-CoV-2 transmission. In this work we model the situation in the United States at present, to demonstrate how the P.1 variant of SARS-CoV-2 can cause a rebound wave of COVID-19 in a matter of months, similar to what happened in Manaus at the beginning of this year. A high burden of morbidity (and likely mortality) remains possible, even if the vaccine is partially effective against new variants and widely accepted. Our modeling suggests that variants that are already present within the population may be capable of quickly defeating the vaccines as a public health intervention, a fatal flaw in strategies that emphasize rapid reopening before achieving control of SARS-CoV-2.
SARS-CoV-2 transmission in K-12 schools in the Vancouver Coastal Health Region: a descriptive epidemiologic study
Authors: Bark Diana , Dhillon Nalin , St-Jean Martin , Kinniburgh Brooke , McKee Geoff , Choi Alexandra
Published: May 2021

Background

There is an urgent need to assess the role of schools in the spread of SARS-CoV-2 in Canada to inform public health measures. We describe the epidemiology of SARS-CoV-2 infection in students and staff in the Vancouver Coastal Health (VCH) region in the first three months of the 2020/2021 academic year, and examine the extent of transmission in schools.

Methods

This descriptive epidemiologic study using contact tracing data included all SARS-CoV-2 cases reported to VCH between September 10 and December 18, 2020 who worked in or attended K-12 schools in-person. Case and cluster characteristics were described.

Results

There were 699 school staff and student cases during the study period, for an incidence of 55 cases per 10,000 population, compared to 73 per 10,000 population in all VCH residents. Among VCH resident staff and student cases, 53% were linked to a household case/cluster, <1.5% were hospitalized and there were no deaths. Out of 699 cases present at school, 26 clusters with school-based transmission resulted in 55 secondary cases. Staff members accounted for 54% of index cases (14/26) while comprising 14% of the school population. Among clusters, 88% had fewer than 4 secondary cases.

Interpretation

COVID-19 incidence in the school population was lower than that of the general population. There were no deaths and severe disease was rare. School-based transmissions of SARS-CoV-2 were uncommon and clusters were small. Our results support the growing body of evidence that schools do not play a major role in the spread of SARS-CoV-2.