bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Specific Childhood Adversities and Symptom Dimensions in People With Psychosis: Systematic Review and Meta-Analysis
Authors: Alameda Luis , Christy Angeline , Rodriguez Victoria , Salazar de Pablo Gonzalo , Thrush Madeleine , Shen Yi , Alameda Beatriz , Spinazzola Edoardo , Iacoponi Eduardo , Trotta Giulia , Carr Ewan , Ruiz Veguilla Miguel , Aas Monica , Morgan Craig , Murray Robin M
Published: December 2020

Despite the accepted link between childhood abuse and positive psychotic symptoms, findings between other adversities, such as neglect, and the remaining dimensions in people with psychosis have been inconsistent, with evidence not yet reviewed quantitatively. The aim of this study was to systematically examine quantitatively the association between broadly defined childhood adversity (CA), abuse (sexual/physical/emotional), and neglect (physical/emotional) subtypes, with positive, negative, depressive, manic, and disorganized dimensions in those with psychosis. A search was conducted across EMBASE, MEDLINE, PsychINFO, and Cochrane Libraries using search terms related to psychosis population, CA, and psychopathological dimensions. After reviewing for relevance, data were extracted, synthesized, and meta-analyzed. Forty-seven papers were identified, including 7379 cases across 40 studies examining positive, 37 negative, 20 depressive, 9 disorganized, and 13 manic dimensions. After adjustment for publication bias, general adversity was positively associated with all dimensions (ranging from r = 0.08 to r = 0.24). Most forms of abuse were associated with depressive (ranging from r = 0.16 to r = 0.32), positive (ranging from r = 0.14 to r = 0.16), manic (r = 0.13), and negative dimensions (ranging from r = 0.05 to r = 0.09), while neglect was only associated with negative (r = 0.13) and depressive dimensions (ranging from r = 0.16 to r = 0.20). When heterogeneity was found, it tended to be explained by one specific study. The depressive dimension was influenced by percentage of women (ranging from r = 0.83 to r = 1.36) and poor-quality scores (ranging from r = −0.21 and r = −0.059). Quality was judged as fair overall. Broadly defined adversity and forms of abuse increase transdimensional severity. Being exposed to neglect during childhood seems to be exclusively related to negative and depressive dimensions suggesting specific effects.
Influence of weaning strategy on behavior, humoral indicators of stress, growth, and carcass characteristics
Authors: Freeman Sharon , Poore Matt , Pickworth Carrie , Alley Mark
Published: December 2020

Weaning is one of the most stressful events a calf experiences in our current beef production system. Its effects may include reduced feed intake, increased activity, slower growth, and increased susceptibility to disease. This study was designed to evaluate weaning after a 7-d placement of nose flaps at 7 mo (N, n = 40) and delaying weaning by 49 d relative to 7-mo weaning (D, n = 39) as alternatives to the industry standard; abrupt weaning at 7 mo of age (A, n = 39). The 4-yr trial utilized Angus and Angus X Senepol steer calves. Calves were randomly assigned to weaning strategy after being stratified by dam parity (heifer/cow), hair coat phenotype (normal/slick), and body weight. Behavioral observations were made on five steers per strategy group per year over the weeks surrounding weaning. Activity levels were determined by accelerometers worn on neck collars. Blood samples were obtained from the observed cattle during the last 2 yr to determine haptoglobin and cortisol concentration. Once weaned, the steers were followed through finishing and carcass characteristics obtained at harvest. Twelve of 38 steers in the N group had sores in their nostrils from the nose flaps when the flaps were removed at weaning of A/N (237 ± 3 d of age). The A and D calves were more active than N calves in the first 2 to 3 d after weaning but settled down to similar activity levels to N by the day 4. The A and D groups were more vocal than N during the same time frame. Cortisol and haptoglobin remained within normal reference ranges. Average daily body weight gain (ADG) was greater for D than A, who in turn had greater ADG than N during the first 42 d after A and N calves were weaned (0.69, 0.54, and 0.37 kg/d for D, A, and N, respectively; P < 0.01). All treatment groups graded Low Choice at harvest and exhibited similar efficiency of gain during growth and finishing (P > 0.2). Based on ADG during the 42 d after weaning, we recommend delaying weaning when available pasture and cow body condition support this strategy. When conditions do not permit delayed weaning, abrupt weaning may be the next viable option based on animal welfare concerns and increased handling to place and remove the flaps. Nose flaps reduced vocalization at weaning but resulted in less postweaning ADG. Based on our data, we suggest that abrupt weaning under the conditions of this study, is less stressful than we perceive it to be, based on calf behavior.
Congenital Scoliosis of the Pediatric Cervical Spine: Characterization of a 17-Patient Operative Cohort
Authors: Toll Brandon J. , Samdani Amer F. , Amanullah Amir A. , Pahys Joshua M. , Janjua Muhammad Burhan , Hwang Steven W.
Published: December 2020

Background:

Congenital cervical scoliosis is rare, and there is a paucity of literature describing surgical outcomes. We report surgical outcomes in a 17-patient cohort with surgical correction for congenital cervical scoliosis and identify risk factors associated with complications.

Methods:

Data were retrospectively collected from a single-center cohort of 17 consecutive patients (9 boys, 8 girls) receiving surgical deformity correction for congenital cervical scoliosis. The mean age at surgery was 7.1±3.4 years with an average follow-up of 3.6±1.1 years.

Results:

There were 24 operations performed on 17 patients, and 4 complications (17%) were reported in the series, including one each of pressure ulcer, asystole, vertebral artery injury, and pseudarthrosis. The mean preoperative major curve angle was 36±20 degrees, which improved to 24±14 degrees (P=0.02). The mean operative time was 8±2 hours with a mean estimated blood loss of 298±690 mL. Halo-gravity traction was used in 5 patients and 6 cases were staged with anterior/posterior procedures.

Conclusions:

Congenital scoliosis of the cervical spine is a complex process. The spinal deformity of this nature can be managed successfully with carefully planned and executed surgical correction.

Level of Evidence:

Level IV—retrospective review.
Modern Day Scurvy in Pediatric Orthopaedics: A Forgotten Illness
Authors: Pan Tommy , Hennrikus Eileen F. , Hennrikus William L.
Published: December 2020

Introduction:

Scurvy, or vitamin C deficiency, is rare. The goal of this study is to highlight the common risk factors and identify the orthopaedic presentation of scurvy in children.

Methods:

A retrospective chart and radiograph review was performed of all patients consulted to the pediatric orthopaedic service from 2010 to 2019 who ultimately had the diagnosis of scurvy confirmed by an abnormally low serum vitamin C level. Data extracted included: patient age, sex, neurological conditions, prematurity, psychiatric conditions, dietary abnormalities, bone pain, arthritis, limb swelling, inability to walk, skin changes, child abuse evaluations, radiographic findings, additional vitamin deficiencies, lab studies, additional tests, response to treatment. Descriptive statistics were performed.

Results:

Nine patients (7 males, 2 females) with scurvy were studied. The average age was 7 years (range 3 to 13 y). The average body mass index was 21.4 (range, 14 to 30). Five had autism, 2 had a neurological disorder. Two had been born premature. Two had a psychiatric disorder. Seven had an abnormal diet. One presented with bone pain. Four presented with limb swelling. Seven had unilateral and 2 had bilateral leg symptoms. Five presented with inability to walk. Six demonstrated skin changes with ecchymosis or petechiae. Three presented with gingival bleeding. Radiographic findings included subperiosteal hematoma in 2, ring epiphysis in 3, Pelkan spurs in 1, metaphyseal white lines (Frankel sign) in 6, and a metaphyseal zone of rarefaction (Trummerfeld zone) in 3. Seven had additional vitamin deficiencies including: A, B1, B6, B9, D, E, K, iron and zinc. Four had a bone marrow biopsy and 1 had lumbar puncture. All were anemic. The average erythrocyte sedimentation rate was 25.7 (range 6 to 35) and C-reactive protein was 1.5 (range 0.55 to 5.64). Six had a computed tomography, 3 had a magnetic resonance imaging. After treatment with vitamin C lasting 3.4 months (range, 2 wk to 7 mo), all symptoms gradually resolved, including leg pain and swelling. All children began to walk.

Conclusion:

The pediatric orthopaedic surgeon should have an increased awareness about the diagnosis of scurvy when consulted on a child with bone pain or inability to walk. The most common orthopaedic presentation was the refusal to bear weight, the most common radiographic finding was the metaphyseal line of increased density (Frankel sign) and treatment with vitamin c supplementation was excellent in all cases.
Refilling Opioid Prescriptions After Pediatric Orthopaedic Surgery: An Analysis of Incidence and Risk Factors
Authors: Meza Blake C. , Swarup Ishaan , Woodard Thaddeus , Cazzulino Alejandro , Talwar Divya , Shah Apurva S.
Published: December 2020

Background:

Understanding which pediatric patients seek opioid refills is crucial as prescription opioid use in childhood is associated with an increased risk of future opioid misuse. Orthopaedic surgeons are optimally positioned to lead the charge in addressing the opioid epidemic. The aim of this study was to describe the incidence of and risk factors associated with requiring opioid refills after pediatric orthopaedic surgery in children.

Methods:

This retrospective case-control study included 1413 patients aged 0 to 18 years that underwent orthopaedic surgery at a single tertiary care children’s hospital and were prescribed opioids at discharge. Using the state Prescription Drug Monitoring Program (PDMP) database, we determined which patients filled additional opioid prescriptions within 6 months following an orthopaedic procedure. Comparisons were made between patients that sought additional opioids and those that did not use bivariate analysis and binomial logistic regression.

Results:

In total, 31 (2.2%) patients sought additional opioid prescriptions a median 41 days postoperatively (range, 2 to 184). Nearly half of these patients obtained refills from providers outside of our institution, suggesting that previous reports using hospital records may underestimate its prevalence. Factors associated with requiring opioid refills included receiving hydromorphone [odds ratio (OR)=3.04, P=0.04] or methadone (OR=38.14, P<0.01) while inpatient, surgery on the axial skeleton (OR=5.42, P=0.01) or lower extremity (OR=2.49, P=0.04), and nonfracture surgery (OR=3.27, P=0.01). Patients who obtained additional opioids received significantly more opioids during their inpatient recovery (32.9 vs. 11.1 morphine equivalents, P<0.01).

Conclusions:

Approximately 2% of children and families obtain additional opioids within 6 months of orthopaedic surgery. The volume of opioids during inpatient hospitalization may predict the need for opioid prescription refills after discharge. Clinicians should maximize efforts to achieve pain control with multimodal analgesia and opioid alternatives, and use caution when administering high-dose opioids during postoperative hospitalization.

Level of Evidence:

Level III—prognostic.
Subtle Slipped Capital Femoral Epiphysis Is not Associated With Idiopathic Cam Morphology
Authors: Morris William Z. , Furdock Ryan J. , Yuh Roger T. , Xie Katherine , Fowers Cody A. , Liu Raymond W.
Published: December 2020

Background:

The etiology of idiopathic cam morphology remains unclear. One theory suggests that subtle slipped capital femoral epiphysis (SCFE) leads to proximal femoral changes resulting in cam morphology. The purpose of this study was to evaluate the association between subtle SCFE and cam morphology in a large osteological collection.

Methods:

We examined 962 cadaveric hips to measure 2 markers of cam morphology, alpha angle and anterior femoral head-neck offset (AHNO), and a validated, objective marker of subtle SCFE deformity (calcar ridge line offset). When the femur is viewed medially, the calcar ridge line extends from the lesser trochanter proximally along the postero-inferior femoral neck and points toward the fovea. In SCFE-like deformity, the fovea deviates posteriorly from this projected line. Pearson correlations were performed to evaluate for possible association of calcar ridge line offset with alpha angle and AHNO. In addition, a multiple regression analysis was performed to determine the influence of age, alpha angle, and AHNO on calcar ridge line offset.

Results:

There was no clinically relevant association between the calcar ridge line offset and alpha angle (r=−0.02, P=0.58) or AHNO (r=0.08, P=0.012). Furthermore, specimens whose calcar ridge line deviated 1 SD above the mean (more SCFE-like deformity) had a smaller alpha angle (46.6±9.1 vs. 48.3±10.6, P=0.046) and greater AHNO (0.83±0.19 vs. 0.77±0.16, P<0.001), both reflecting less cam-like morphology. On regression analysis, increasing age and increasing AHNO (decreased cam morphology) predicted increased calcar ridge line offset, though the model accounted for only 1.2% of the variance.

Conclusions:

Subtle SCFE-like deformity, as objectively measured from the calcar ridge line, was not predictive of more cam-like morphology, and in fact mild opposite associations were found. Further study is needed to identify other potential etiologies of idiopathic cam morphology.

Clinical Relevance:

We present evidence from a large, well-documented osteological collection indicating that subtle SCFE is not associated with idiopathic cam morphology.
Surgical Strategy of Pediatric Benign Sacral Tumors
Authors: Wang Jun , Du Zhiye , Yang Rongli , Tang Xiaodong , Yan Taiqiang , Guo Wei
Published: December 2020

Background:

Primary benign osseous tumors and tumor-like lesions at the sacrum are rare in the pediatric population and exact surgical strategy is still unclear. In this study, we evaluate the outcome for pediatric patients with benign tumors and tumor-like lesions at the sacrum who were receiving surgical treatment according to our proposed surgical strategy and classification.

Methods:

We analyzed 49 pediatric patients with sacral benign tumors or tumor-like lesions aged 18 years and below from 2005 to 2018. There were 23 men and 26 women with a mean age of 14.0±3.8 years. Nineteen patients had giant cell tumors (GCTs), 9 aneurysmal bone cysts, 5 osteoblastomas, 5 neurogenic tumors, 3 hemangiomas, 3 teratomas, 2 Langerhans cell histiocytosis, 1 chondroblastoma, 1 fibrous dysplasia, and 1 GCT of tendon sheath. We proposed our surgical plan and surgical classification for pediatric patients with sacral benign tumors or tumor-like lesions.

Results:

The mean follow-up duration was 6.2 years (range, 1.0 to 18.9 y). GCTs (39%, 19/49) and primary aneurysmal bone cysts (18%, 9/49) are the top 2 common histologic types. Preoperative selective arterial embolization (SAE) was performed in 12 cases and 24 patients received intraoperative aortic balloon occlusion (ABO) as the preoperative surgical plan. Furthermore, according to tumor location at the sacrum, we classified surgical excision of sacral benign tumors and tumor-like lesions into 3 types. Fourteen cases were classified as type I, 27 as type II, 3 as type III, and 5 patients with neurogenic tumors cannot be classified into this surgical classification. Ten patients had wound complications. Two had femoral artery thrombosis because of ABO application. One had mechanical failure. Rate of local recurrence was 16%. Seven patients with GCTs and 1 with neurogenic tumor had local recurrence. No patient died of disease at the last follow-up. For the assessment of neurological function, the rate of neurological dysfunction was 12% (6/49). Four cases had urinary incontinence, 3 fecal incontinence, and 3 had bowel obstruction. Next, univariate analysis for influence of preoperative SAE and intraoperative ABO on complications demonstrated that both of them exerted no significant influence on the occurrence of oncological and nononcological complications.

Conclusions:

The proposed surgical strategy can provide an excellent therapeutic effect for pediatric benign tumors and tumor-like lesions at the sacrum. Preoperative SAE and intraoperative ABO can safeguard pediatric patients with high vascularity of benign tumor at the sacrum during the operation.

Level of Evidence:

Level IV.
Lung cancer screening: intention to participate and acceptability among Belgian smokers
Authors: Kellen Eliane , Gabriels Suzanne , Van Hal Guido , Goossens Mathijs C.
Published: December 2020

Objective

Next to the obvious benefits of tobacco-use cessation, lung cancer screening using low-dose computed tomography (LDCT) scans has been proposed as a means to lower lung cancer burden. Achieving an impact of any cancer screening program on cancer-specific mortality largely depends on the uptake. The aim of this study was to estimate the acceptability and intention to participate in a lung cancer screening program among Belgian current or former smokers.

Methods

A cross-sectional online survey was carried out among adults from the Belgian population. Sampling took place within an existing online panel.

Results

In total, 83.6% of all respondents (n = 2727), including current or former smokers and never smokers, believed that offering lung cancer screening to current or former smokers is a good idea. 84.3% of all current or former smokers (n = 1534) answered that they would likely or very likely participate in a screening program for lung cancer. The majority of current smokers that were willing to be screened said they would also want to receive tobacco-use cessation counseling in parallel with screening (71.8%; n = 486), whereas 9% (n = 61) would decline.

Conclusions

These findings suggest that a Belgian lung cancer screening program would be acceptable and could be well-attended by current or former smokers. Further research should focus on how smokers can be best reached to propose screening, and how tobacco-use cessation counseling can be successfully integrated in a lung cancer screening program.
A Randomized Clinical Study (SEECASE) to Assess Efficacy, Safety, and Tolerability of NOV03 for Treatment of Dry Eye Disease
Authors: Tauber Joseph , Wirta David L. , Sall Kenneth , Majmudar Parag A. , Willen Daniela , Krösser Sonja ,   for the SEECASE study group
Published: December 2020

Purpose:

NOV03 has a unique dual mode of action to address dry eye disease (DED) associated with meibomian gland dysfunction. SEECASE evaluated the efficacy, safety, and tolerability of NOV03 at 2 dosing regimens compared with a saline comparator in patients with DED.

Methods:

SEECASE was a prospective, multicenter, randomized, double-masked, saline-controlled clinical study. A total of 336 DED patients [tear film breakup time ≤5 seconds, abnormal meibum secretion, total corneal fluorescein staining (tCFS) score of 4 ≤ X ≤ 11 (National Eye Institute scale), Schirmer of ≥5 mm] were randomized in a 2:2:1:1 manner to NOV03 4 times daily (QID), NOV03 twice daily (BID), saline BID, and saline QID, respectively. The primary efficacy endpoint was tCFS staining at 8 weeks for both regimens. Secondary endpoints included visual analog scales and the Ocular Surface Disease Index questionnaire for symptom assessment.

Results:

The study met its primary endpoint, change from baseline of tCFS over control, for both dosing regimens QID and BID (P < 0.001 and P = 0.009, respectively). NOV03 also showed pronounced improvement in various symptoms. For the Eye Dryness Score, changes from baseline were statistically significant compared with those of the control at week 8 [P < 0.001 (QID) and P = 0.002 (BID)]. Benefits on tCFS and symptoms started at 2 weeks after start of treatment and were maintained over the study duration. The effects were dosing schedule dependent. NOV03 was well tolerated with instillation site reactions below 3% in both treatment regimes.

Conclusions:

The SEECASE study demonstrated that NOV03 improves signs and symptoms in patients with highly symptomatic evaporative dry eye disease.
Assessment of Antimicrobial Activity of Dehydrated Amniotic Membrane in Infectious Keratitis: A Small Retrospective Case Series and In Vitro Study
Authors: Oji Nnaoma M. , Lin Yijie B. , Lee Michele D. , Cevallos Ada V. , Keenan Jeremy D. , Seitzman Gerami D.
Published: December 2020

Purpose:

To describe a small case series of infectious keratitis with poor visual outcomes after amniotic membrane (AM) placement and to prospectively evaluate whether AM demonstrates antibacterial activity in vitro against pathogens commonly isolated from infectious corneal ulcers.

Methods:

A retrospective case series and in vitro study of antibacterial activity of dehydrated AM using disk diffusion and measurement of inhibitory zones for bacterial assessment and inverted microscopy analysis forAcanthamoebasp. growth.

Results:

Three cases of known etiology infectious keratitis are described where the clinical presentation worsened after treatment with AM. In vitro analysis of dehydrated AM, with and without a soft contact lens, demonstrated no inhibition of growth againstPseudomonas aeruginosaorStreptococcus pneumoniae.There was minimal growth inhibition ofStaphylococcus aureus, although these zones of inhibition were much smaller than that surrounding the positive control. ForAcanthamoebasp., solubilized, dehydrated AM did not alter cyst density.

Conclusions:

In an in vitro analysis, dehydrated AM did not provide evidence for a potentially clinically meaningful antibacterial effect against organisms commonly isolated from corneal ulcers.
Silk Suture Granuloma 37 Years After Scleral Buckle Surgery: A Case Report
Authors: Zein Mike , Theotoka Despoina , Wall Sarah , Galor Anat , Cabot Florence , Patel Umangi , Dubovy Sander , Karp Carol L.
Published: December 2020

Purpose:

To present a rare presentation of pyogenic granuloma arising almost 4 decades after a scleral buckle for retinal detachment.

Method:

We describe the clinical presentation, diagnostic workup, and management of a suspicious conjunctival lesion in an immunocompromised patient. We report the histopathological findings and the postoperative outcome.

Results:

A 58-year-old man with human immunodeficiency virus presented for evaluation of a possible malignant conjunctival lesion in the left eye. The patient reported that the lesion had appeared 1.5 months before presentation with significant growth over the past month. The patient denied any trauma to the eye other than an ocular history of retinal detachment repair with scleral buckle 37 years earlier. Clinical examination revealed a pink, fleshy, mobile, and lobulated conjunctival lesion measuring 7 mm by 10 mm, emanating from the superior–nasal bulbar quadrant. A high-resolution optical coherence tomography revealed highly cellular infiltrate and hyperreflective mass with significant posterior shadowing. Further exploration of the lesion revealed a white, stringy, cauliflower-like material on the underside of the lesion. Surgical excision and pathology subsequently confirmed a diagnosis of pyogenic granuloma with remnants of silk suture.

Conclusions:

A diagnosis of pyogenic granuloma secondary to retained silk sutures should be considered in patients with a history of intraocular surgery irrespective of other risk factors and length of time since procedure.
The liver in COVID-19: prevalence, patterns, predictors, and impact on outcomes of liver test abnormalities
Authors: Goel Harsh , Harmouch Farah , Garg Kawish , Saraiya Pooja , Daly Timothy , Kumar Ashish , Hippen John T.
Published: December 2020

Background

Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century, with ≈35 million cases, and more than 1 million deaths globally. Though predominantly a lower respiratory illness, other organ injuries are well-recognized. Among these, liver injury is of major interest.

Objective

To define prevalence, pattern, predictors, and impact of liver injury among patients hospitalized with COVID-19.

Methods

Demographic, clinical, and biochemical data were collected retrospectively among patients admitted to St. Luke’s University Hospital with COVID-19 between 1 March and 18 April 2020. Association of liver tests (LTs) with mortality and need for mechanical ventilation, adjusted for demographic, clinical and biochemical predictors, was examined.

Results

Data were available on 551 patients. Prevalence of any or ≥3 × upper limit of normal transaminase elevation on was 61.2 and 9.4% on admission, and 72.1 and 22.4% at peak. Bilirubin and alkaline phosphatase elevations were less common on admission (11.4 and 12.6%, respectively), and at peak (17.7 and 22%, respectively). All liver test (LT) elevations were consistently predicted by inflammatory markers. Hyperbilirubinemia predicted mortality on admission and at peak. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) had opposite impact on mortality with AST positively, and ALT negatively associated with mortality. Hence, besides hyperbilirubinemia, AST:ALT ratio emerged as the best marker for mortality among the LTs.

Conclusion

LT elevations among patients presenting with COVID-19 are very common, though majority are mild. Admission and peak bilirubin ≥1 mg/dl, as well as admission and peak AST:ALT ratio were significant predictors of mortality, along with age, myocardial injury, and chronic medical illness.
Microbes in human oral cavity: a review
Authors: Sarmah Rajeev , Khan Reyaz A. , Devi Kangjam R.
Published: December 2020

The oral cavity being one of the important opening encounter huge number of microorganisms via air, water and food. Some of them establish, grow and multiply, form communities inside the cavity. The selection and growth of these microorganisms depend upon the physiochemical environment in the cavity. Various molecules of the host and resident microorganisms are responsible for the environmental conditions. Literatures indicate that change in this molecular content in the cavity may likely change the microbial communities in it. Therefore, in case of various diseased conditions/changed food habit may invite changes in microorganisms inside the oral cavity. Thus association of certain microorganisms or increased number of certain microorganisms in the oral cavity may be a good indicator for disease diagnosis.
Combined RT-qPCR and Pyrosequencing of a SARS-CoV-2 Spike Glycoprotein Polybasic Cleavage Motif Uncovers Rare Pediatric COVID-19 Spectrum Diseases of Unusual Presentation
Authors: Weil Patrick Philipp , Hentschel Jacqueline , Schult Frank , Pembaur Anton , Ghebremedhin Beniam , Mboma Olivier , Heusch Andreas , Reuter Anna-Christin , Müller Daniel , Wirth Stefan , Aydin Malik , Jenke Andreas C. W. , Postberg Jan
Published: December 2020

Background

Surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is essential for the global containment measures with regard to the ongoing pandemic. Diagnostic gold standard is currently reverse transcription of the (+)RNA genome and subgenomic RNAs and subsequent quantitative polymerase chain reaction (RT-qPCR) from nasopharyngeal swabs or bronchoalveolar lavages. In order to further improve the diagnostic accuracy, particularly for the reliable discrimination between negative and false-negative specimens, we propose the combination of the RT-qPCR workflow with subsequent pyrosequencing of a S-gene amplicon. This extension might add important value mainly in cases with low SARS-CoV-2 load, where RT-qPCR alone can deliver conflicting results.s

Results

We successfully established a combined RT-qPCR and S-gene pyrosequencing method which can be optionally exploited after routine diagnostics or for epidemiologic studies. This allows a more reliable interpretation of conflicting RT-qPCR results in specimens with relatively low viral loads and close to the detection limits of qPCR (CT values >30). After laboratory implementation and characterization of a best practice protocol we tested the combined method in a large pediatric cohort from two German medical centers (n=769). Pyrosequencing after RT-qPCR enabled us to uncover 6 previously unrecognized cases of pediatric SARS-CoV-2 associated diseases, partially exhibiting unusual and heterogeneous presentation. Moreover, it is notable that in the course of RT-qPCR/pyrosequencing method establishment we did not observe any case of false-positive diagnosis when confirmed SARS-CoV-2-positive specimens were used from foregoing routine testing.

Conclusions

The proposed protocol allows a specific and sensitive detection of SARS-CoV-2 close to the detection limits of RT-qPCR. Combined RT-qPCR/pyrosequencing does not negatively affect preceding RT-qPCR pipeline in SARS-CoV-2 diagnostics and can be optionally applied in routine to inspect conflicting RT-qPCR results.
Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Integrated Bioinformatics Analysis and Molecular Docking Experiments
Authors: Vastrad Basavaraj , Vastrad Chanabasayya , Tengli Anandkumar
Published: December 2020

The current investigation aimed to mine therapeutic molecular targets that play an key part in the advancement of pancreatic ductal adenocarcinoma (PDAC). The expression profiling by high throughput sequencing dataset profile GSE133684 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Limma package of R was used to identify differentially expressed genes (DEGs). Functional enrichment analysis of DEGs were performed. Protein-protein interaction (PPI) networks of the DEGs were constructed. An integrated gene regulatory network was built including DEGs, microRNAs (miRNAs), and transcription factors. Furthermore, consistent hub genes were further validated. Molecular docking experiment was conducted. A total of 463 DEGs (232 up regulated and 231 down regulated genes) were identified between very early PDAC and normal control samples. The results of Functional enrichment analysis revealed that the DEGs were significantly enriched in vesicle organization, secretory vesicle, protein dimerization activity, lymphocyte activation, cell surface, transferase activity, transferring phosphorus-containing groups, hemostasis and adaptive immune system. The PPI network and gene regulatory network of up regulated genes and down regulated genes were established, and hub genes were identified. The expression of hub genes (CCNB1, FHL2, HLA-DPA1 and TUBB1) were also validated to be differentially expressed among PDAC and normal control samples. Molecular docking experiment predicted the novel inhibitory molecules for CCNB1 and FHL2. The identification of hub genes in PDAC enhances our understanding of the molecular mechanisms underlying the progression of this disease. These genes may be potential diagnostic biomarkers and/or therapeutic molecular targets in patients with PDAC.
Low vitamin K status predicts mortality in a cohort of 138 hospitalized patients with COVID-19
Authors: Linneberg A , Kampmann FB , Israelsen SB , Andersen LR , Jørgensen HL , Sandholt H , Jørgensen NR , Thysen SM , Benfield T
Published: December 2020

It has recently been hypothesised that Vitamin K could play a role in COVID-19. We aimed to test the hypothesis that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls; and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 140 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional Vitamin K status in peripheral tissue. Fourty-three patients died within 90-days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low Vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.50, 95% CI: 1.03; 2.18). In conclusion, we found that low Vitamin K status predicted mortality in patients with COVID-19 supporting a potential role of Vitamin K in COVID-19.
Renin-angiotensin system blockers and mortality in COVID-19: a territory-wide study from Hong Kong
Authors: Zhou Jiandong , Tse Gary , Lee Sharen , Wong Wing Tak , Wang Xingsong , Wu William KK , Liu Tong , Cao Zhidong , Zeng Daniel Dajun , Wong Ian Chi Kei , Cheung Bernard Man Yung , Zhang Qingpeng
Published: December 2020

Aims

Renin–angiotensin system blockers such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of adverse outcomes in COVID-19. In this study, the relationships between ACEI/ARB use and COVID-19 related mortality were examined.

Methods

Consecutive patients diagnosed with COVID-19 by RT-PCR at the Hong Kong Hospital Authority between 1st January and 28th July 2020 were included.

Results

This study included 2774 patients. The mortality rate of the COVID-19 positive group was 1.5% (n=42). Those who died had a higher median age (82.3[76.5-89.5] vs. 42.9[28.2-59.5] years old; P<0.0001), more likely to have baseline comorbidities of cardiovascular disease, diabetes mellitus, hypertension, and chronic kidney disease (P<0.0001). They were more frequently prescribed ACEI/ARBs at baseline, and steroids, lopinavir/ritonavir, ribavirin and hydroxychloroquine during admission (P<0.0001). They also had a higher white cell count, higher neutrophil count, lower platelet count, prolonged prothrombin time and activated partial thromboplastin time, higher D-dimer, troponin, lactate dehydrogenase, creatinine, alanine transaminase, aspartate transaminase and alkaline phosphatase (P<0.0001). Multivariate Cox regression showed that age, cardiovascular disease, renal disease, diabetes mellitus, the use of ACEIs/ARBs and diuretics, and various laboratory tests remained significant predictors of mortality.

Conclusions

We report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use. Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.

Key Points

We report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use.

Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.
Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses
Authors: Vastrad Basavaraj , Vastrad Chanabasayya , Kotturshetti Iranna
Published: December 2020

Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. Pathway and GO enrichment analyses of DEGs were performed. Furthermore, the protein-protein interaction (PPI) network was predicted using the IntAct Molecular Interaction Database and visualized with Cytoscape software. In addition, hub genes and important modules were selected based on the network. Finally, we constructed target genes - miRNA regulatory network and target genes - TF regulatory network. Hub genes were validated. A total of 891 DEGs 448 of these DEGs presented significant up regulated, and the remaining 443 down regulated were obtained. Pathway enrichment analysis indicated that up regulated genes were mainly linked with glutamine degradation/glutamate biosynthesis, while the down regulated genes were involved in melatonin degradation. GO enrichment analyses indicated that up regulated genes were mainly linked with chemical synaptic transmission, while the down regulated genes were involved in regulation of immune system process. hub and target genes were selected from the PPI network, modules, and target genes - miRNA regulatory network and target genes - TF regulatory network namely YWHAZ, GABARAPL1, EZR, CEBPA, HSPB8, TUBB2A and CDK14. The current study sheds light on the molecular mechanisms of sCJD and may provide molecular targets and diagnostic biomarkers for sCJD.
Predicting the Evolution of COVID-19 Mortality Risk: a Recurrent Neural Network Approach
Authors: Villegas Marta , Gonzalez-Agirre Aitor , Gutiérrez-Fandiño Asier , Armengol-Estapé Jordi , Carrino Casimiro Pio , Pérez Fernández David , Soares Felipe , Serrano Pablo , Pedrera Miguel , García Noelia , Valencia Alfonso
Published: December 2020

Abstract

Background

The propagation of COVID-19 in Spain prompted the declaration of the state of alarm on March 14, 2020. On 2 December 2020, the infection had been confirmed in 1,665,775 patients and caused 45,784 deaths. This unprecedented health crisis challenged the ingenuity of all professionals involved. Decision support systems in clinical care and health services management were identified as crucial in the fight against the pandemic.

Methods

This study applies Deep Learning techniques for mortality prediction of COVID-19 patients. Two datasets with clinical information (medication, laboratory tests, vital signs etc.) were used. They are comprised of 2,307 and 3,870 COVID-19 infected patients admitted to two Spanish hospital chains. Firstly, we built a sequence of temporal events gathering all the clinical information for each patient. Next, we used the temporal sequences to train a Recurrent Neural Network (RNN) model with an attention mechanism exploring interpretability. We conducted extensive experiments and trained the RNNs in different settings, performing hyperparameter search and cross-validation. We ensembled resulting RNNs to reduce variability and enhance sensitivity.

Results

We assessed the performance of our models using global metrics, by averaging the performance across all the days in the sequences. We also measured day-by-day metrics starting from the day of hospital admission and the outcome day and evaluated the daily predictions. Regarding sensitivity, when compared to more traditional models, our best two RNN ensemble models outperform a Support Vector Classifier in 6 and 16 percentage points, and Random Forest in 23 and 18 points. For the day-by-day predictions from the outcome date, the models also achieved better results than baselines showing its ability towards early predictions.

Conclusions

We have shown the feasibility of our approach to predict the clinical outcome of patients infected with SARS-CoV-2. The result is a time series model that can support decision-making in healthcare systems and aims at interpretability. The system is robust enough to deal with real world data and it is able to overcome the problems derived from the sparsity and heterogeneity of the data. In addition, the approach was validated using two datasets showing substantial differences. This not only validates the robustness of the proposal but also meets the requirements of a real scenario where the interoperability between hospitals’ datasets is difficult to achieve.
Privacy-first health research with federated learning
Authors: Sadilek Adam , Liu Luyang , Nguyen Dung , Kamruzzaman Methun , Rader Benjamin , Ingerman Alex , Mellem Stefan , Kairouz Peter , Nsoesie Elaine O. , MacFarlane Jamie , Vullikanti Anil , Marathe Madhav , Eastham Paul , Brownstein John S. , Howell Michael , Hernandez John
Published: December 2020

Privacy protection is paramount in conducting health research. However, studies often rely on data stored in a centralized repository, where analysis is done with full access to the sensitive underlying content. Recent advances in federated learning enable building complex machine-learned models that are trained in a distributed fashion. These techniques facilitate the calculation of research study endpoints such that private data never leaves a given device or healthcare system. We show on a diverse set of health studies that federated models can achieve the same level of accuracy, precision, and generalizability, and result in the same interpretation as standard centralized statistical models whilst achieving significantly stronger privacy protections. This work is the first to apply modern and general federated learning methods to clinical and epidemiological research -- across a spectrum of units of federation and model architectures. As a result, it enables health research participants to remain in control of their data and still contribute to advancing science -- aspects that used to be at odds with each other.
Comparing Non-Communicable Disease Risk Factors in Asian Migrants and Native Koreans
Authors: Piao Heng , Yun Jae Moon , Shin Aesun , Kang Daehee , Cho Belong
Published: December 2020

Importance

Regarding international migrants, the theories of healthy migration effect and sick migration effect both exist; thus, assessing the health of international migrants is crucial in the Republic of Korea, Asia, and even worldwide.

Objective

To compare non-communicable disease risk factors among Asian migrants in Korea and the Korean population.

Design

A cross-sectional (2015) and longitudinal (2009□2015) observational study.

Setting

Population-wide analysis using the National Health Information Database of the Korean National Health Insurance Service for 2009□2015.

Participants

Asian migrants (n=987,214) in Korea and Korean nationals (n=1,693,281) aged ≥20 years were included. In addition, Asian migrants were divided into Chinese, Japanese, Filipino, Vietnamese, and other Asian migrants.

Exposure

The nationality of Asian migrants compared with Koreans.

Main Outcomes and Measures

The prevalence of non-communicable disease risk factors, such as current smoking, obesity, diabetes, and hypertension, in 2015 was analyzed. Regarding the age-adjusted prevalence, direct age standardization was conducted separately by sex using 10-year age bands; the World Standard Population was used as the standard population.

Results

Among participants aged ≥20 years, the age-adjusted prevalence of current smoking was higher among Chinese migrant men than among Korean men (P<0.001) and among other Asian migrant women than among Korean women (P<0.001). The age-adjusted prevalence of obesity was higher in Chinese, Filipino, and other Asian migrant women than in Korean women (P<0.001, P=0.002, and P<0.001, respectively). Among participants aged 20–49 years, the age-adjusted prevalence of diabetes and hypertension was higher in Filipino migrant women than in Korean women (P=0.009 and P<0.001, respectively).

Conclusion and Relevance

The current status of smoking and obesity among Asian migrants of specific nationalities is worse than that among native Koreans. Moreover, the health inequalities among Filipino migrant women in Korea, especially those aged 20–49 years, should be addressed.

Key Points

Question

Do international migrants in Korea have a health advantage regarding non-communicable disease risk factors?

Findings

Among participants aged ≥20 years, the problem of current smoking among Chinese migrant men and other Asian migrant women and that of obesity among Chinese, Filipino, and other Asian migrant women in Korea needs to be addressed. The prevalence of diabetes and hypertension was higher among Filipino migrant women than among Korean women in the 20–49-year age group.

Meaning

The relationships between Asian migrant nationality and non-communicable disease risk factors provide evidence for targeting high-risk groups and improving policy development in Korea.
Functional imaging to guide network-based TMS treatments: toward a tailored medicine approach in Alzheimer’s disease
Authors: Bagattini Chiara , Brignani Debora , Bonnì Sonia , Gasparotti Roberto , Pievani Michela
Published: December 2020

INTRODUCTION

Transcranial magnetic stimulation (TMS) has gained increasing attention as a potential therapeutic strategy in Alzheimer’s disease (AD). Among factors determining a clinical response, the choice of the stimulation site represents a key point. In this proof of concept study, we prove the feasibility of a tailored TMS targeting approach for AD, which stems from a network-based perspective. Based on functional imaging, the procedure allows to extract individual optimal targets meanwhile accounting for functional variability.

METHODS

Single-subject resting-state fMRI was used to extract individual target coordinates of two networks primarily affected in AD, the default mode and the fronto-parietal network. The localization of these targets was compared to that of traditional group-level approaches and tested against varying degrees of TMS focality.

RESULTS

The distance between individual fMRI-derived coordinates and traditionally-defined targets was significant for a focality <12mm, but not for >20mm. Comparison with anatomical labels confirmed a lack of 1:1 correspondence between anatomical and functional targets.

DISCUSSION

The proposed network-based fMRI-guided TMS approach allows targeting disorder-specific networks meanwhile accounting for inter-individual functional variability in Alzheimer’s disease. This approach might represent a step toward tailored TMS interventions for AD.