bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Biomarkers of Habitual Alcohol Intake and Associations With Risk of Pancreatic and Liver Cancers and Liver Disease Mortality
Authors: Loftfield Erikka , Stepien Magdalena , Viallon Vivian , Trijsburg Laura , Rothwell Joseph A , Robinot Nivonirina , Biessy Carine , Bergdahl Ingvar A , Bodén Stina , Schulze Matthias B , Bergman Manuela , Weiderpass Elisabete , Schmidt Julie A , Zamora-Ros Raul , Nøst Therese H , Sandanger Torkjel M , Sonestedt Emily , Ohlsson Bodil , Katzke Verena , Kaaks Rudolf , Ricceri Fulvio , Tjønneland Anne , Dahm Christina C , Sánchez Maria-Jose , Trichopoulou Antonia , Tumino Rosario , Chirlaque María-Dolores , Masala Giovanna , Ardanaz Eva , Vermeulen Roel , Brennan Paul , Albanes Demetrius , Weinstein Stephanie J , Scalbert Augustin , Freedman Neal D , Gunter Marc J , Jenab Mazda , Sinha Rashmi , Keski-Rahkonen Pekka , Ferrari Pietro
Published: May 2021

Background

Alcohol is an established risk factor for several cancers, but modest alcohol-cancer associations may be missed because of measurement error in self-reported assessments. Biomarkers of habitual alcohol intake may provide novel insight into the relationship between alcohol and cancer risk.

Methods

Untargeted metabolomics was used to identify metabolites correlated with self-reported habitual alcohol intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition (EPIC; n = 454). Statistically significant correlations were tested in independent datasets of controls from case-control studies nested within EPIC (n = 280) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC; n = 438) study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of alcohol-associated metabolites and self-reported alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer, and liver disease mortality in the contributing studies.

Results

Two metabolites displayed a dose-response association with self-reported alcohol intake: 2-hydroxy-3-methylbutyric acid and an unidentified compound. A 1-SD (log2) increase in levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR = 2.54, 95% CI = 1.51 to 4.27) and pancreatic cancer (OR = 1.43, 95% CI = 1.03 to 1.99) in EPIC and liver cancer (OR = 2.00, 95% CI = 1.44 to 2.77) and liver disease mortality (OR = 2.16, 95% CI = 1.63 to 2.86) in ATBC. Conversely, a 1-SD (log2) increase in questionnaire-derived alcohol intake was not associated with HCC or pancreatic cancer in EPIC or liver cancer in ATBC but was associated with liver disease mortality (OR = 2.19, 95% CI = 1.60 to 2.98) in ATBC.

Conclusions

2-hydroxy-3-methylbutyric acid is a candidate biomarker of habitual alcohol intake that may advance the study of alcohol and cancer risk in population-based studies.
Human tRNAs with inosine 34 are essential to efficiently translate eukarya-specific low-complexity proteins
Authors: Torres Adrian Gabriel , Rodríguez-Escribà Marta , Marcet-Houben Marina , Santos Vieira Helaine Graziele , Camacho Noelia , Catena Helena , Murillo Recio Marina , Rafels-Ybern Àlbert , Reina Oscar , Torres Francisco Miguel , Pardo-Saganta Ana , Gabaldón Toni , Novoa Eva Maria , Ribas de Pouplana Lluís
Published: May 2021

The modification of adenosine to inosine at the wobble position (I34) of tRNA anticodons is an abundant and essential feature of eukaryotic tRNAs. The expansion of inosine-containing tRNAs in eukaryotes followed the transformation of the homodimeric bacterial enzyme TadA, which generates I34 in tRNAArg and tRNALeu, into the heterodimeric eukaryotic enzyme ADAT, which modifies up to eight different tRNAs. The emergence of ADAT and its larger set of substrates, strongly influenced the tRNA composition and codon usage of eukaryotic genomes. However, the selective advantages that drove the expansion of I34-tRNAs remain unknown. Here we investigate the functional relevance of I34-tRNAs in human cells and show that a full complement of these tRNAs is necessary for the translation of low-complexity protein domains enriched in amino acids cognate for I34-tRNAs. The coding sequences for these domains require codons translated by I34-tRNAs, in detriment of synonymous codons that use other tRNAs. I34-tRNA-dependent low-complexity proteins are enriched in functional categories related to cell adhesion, and depletion in I34-tRNAs leads to cellular phenotypes consistent with these roles. We show that the distribution of these low-complexity proteins mirrors the distribution of I34-tRNAs in the phylogenetic tree.
Justifying quarantine in preventing the spread of COVID-19 in healthcare
Authors: Kerr G M , Crowley M , O’Reilly E J , Cunningham C
Published: May 2021

Background

The first COVID-19-positive patient was identified in Ireland on 29 February 2020 (Department of Health, Government of Ireland; https://www.gov.ie/en/pressrelease/2f75fd-statement-from-the-national-public-healthemergency-team-sat-29-feb/). Healthcare worker (HCW) quarantining became a core intervention for those identified as ‘close contacts’ to reduce onward transmission within the workplace to patients and colleagues. Whether a quarantining strategy could be justified at a time when there was an increased demand for the services of HCWs remained unknown.

Aims

To establish whether quarantining staff away from a healthcare setting during a pandemic is justified.

Methods

This retrospective study examined close contacts of COVID-19-positive index cases (both residents and HCWs) in a community hospital over a 4-week period from 1 to 28 April 2020. Close contacts were identified in accordance with national guidelines. Zones of the hospital were examined to determine the number of COVID-positive index cases and their close contacts. A cumulative result for the hospital was recorded.

Results

While outcomes varied over time, per zone and per HCW category, the overall conversion rate from close contact to an index case was 30%.

Conclusions

This study vindicates the policy of quarantining close contact HCWs from their workplaces as they pose a significant threat to both their patients and fellow workers.
New Examples Of Shrinking Laplacian Solitons
Authors: Nicolini Marina
Published: May 2021

We give a one-parameter family of examples of shrinking Laplacian solitons, which are the second known solutions to the closed G2-Laplacian flow with a finite-time singularity. The torsion forms and the Laplacian and Ricci operators of a large family of G2-structures on different Lie groups are also studied. We apply these formulas to prove that, under a suitable extra condition, there is no closed eigenform for the Laplacian on such family.
Proteomic characteristics of beryllium sulfate-induced differentially expressed proteins in rats
Authors: Zheng Kai , Cai Ying , Lei Yuandi , Liu Yanping , Sun Zhanbing , Wang Ye , Xu Xinyun , Zhang Zhaohui
Published: May 2021

Sprague Dawley rats were exposed to beryllium sulfate (BeSO4), and proteomic and bioinformatic techniques were applied to screen for differentially expressed proteins in their lung tissue and serum. A total of 12 coexpression modules were constructed for 18 samples with 2333 proteins. Four modules were found to have significant differences in the regulation of protein coexpression modules in the serum following exposure to BeSO4. A further three modules had significant differences in the regulation of protein coexpression modules in the lung tissues. Five modules with good correlation were obtained by calculating the gene significance and module membership values, whereas these module Hub proteins included: Hspbp1, Rps15a, Srsf2, Hadhb, Elmo3, Armt1, Rpl18, Afap1L1, Eif3d, Eif3c, and Rps3. The five proteins correlating highest with the Hub proteins in the lung tissue and serum samples were obtained using string analysis. KEGG and GO enrichment analyses showed that these proteins are mainly involved in ribosome formation, apoptosis, cell cycle regulation, and tumor necrosis factor regulation. By analyzing the biological functions of these proteins, proteins that can be used as biomarkers, such as Akt1, Prpf19, Cct2, and Rpl18, are finally obtained.
COVID-19 and telehealth
Authors: Summer Georgianne , Adelman Deborah S. , Fant Catherine
Published: May 2021

In the third and final article in this series, patient and provider dynamics are explored, built from real-life telehealth experiences. The Four Habits Model is utilized to examine the virtual visit.
Distal Femur Replacement Versus Open Reduction and Internal Fixation for Treatment of Periprosthetic Distal Femur Fractures: A Systematic Review and Meta-Analysis
Authors: Wadhwa Harsh , Salazar Brett P. , Goodnough L. Henry , Van Rysselberghe Noelle L. , DeBaun Malcolm R. , Wong Hong-Nei , Gardner Michael J. , Bishop Julius A.
Published: May 2021

Objective:

To compare complications and functional outcomes of treatment with primary distal femoral replacement (DFR) versus open reduction and internal fixation (ORIF).

Data Sources:

PubMed, Embase, and Cochrane databases were searched for English language studies up to May 19, 2020, identifying 913 studies.

Study Selection:

Studies that assessed complications of periprosthetic distal femur fractures with primary DFR or ORIF were included. Studies with sample size ≤5, mean age <55, nontraumatic indications for DFR, ORIF with nonlocking plates, native distal femoral fractures, or revision surgeries were excluded. Selection adhered to the PRISMA criteria.

Data Extraction:

Study quality was assessed using previously reported criteria. There were 40 Level IV studies, 17 Level III studies, and 1 Level II study.

Data Synthesis:

Fifty-eight studies with 1484 patients were included in the meta-analysis. Complications assessed {incidence rate ratio [IRR] [95% confidence interval (CI)]: 0.78 [0.59–1.03]} and reoperation or revision [IRR (95% CI): 0.71 (0.49–1.04)] were similar between the DFR and ORIF cohorts. The mean knee range of motion was greater in the ORIF cohort (DFR: 90.47 vs. ORIF: 100.36, P < 0.05). The mean Knee Society Score (KSS) (DFR: 79.41 vs. ORIF: 82.07, P = 0.35) and return to preoperative ambulatory status were similar [IRR (95% CI): 0.82 (0.48–1.41)].

Conclusions:

In comparing complications among patients treated for periprosthetic distal femur fracture with DFR or ORIF, there was no difference between the groups. There were also no differences in functional outcomes, although knee range of motion was greater in the ORIF group. This systematic review and meta-analysis highlights the need for future prospective trials evaluating the outcomes of these divergent treatment strategies.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Modified Early Warning Score: A Useful Marker of Neurological Worsening but Unreliable Predictor of Sepsis in the Neurocritically Ill—A Retrospective Cohort Study
Authors: Hester Jeannette , Youn Teddy S. , Trifilio Erin , Robinson Christopher P. , Babi Marc-Alain , Ameli Pouya , Roth William , Gatica Sebastian , Pizzi Michael A. , Gennaro Aimee , Crescioni Charles , Maciel Carolina B. , Busl Katharina M.
Published: May 2021

OBJECTIVES:

To determine the performance of the Modified Early Warning Score and Modified Early Warning Score-Sepsis Recognition Score to predict sepsis, morbidity, and mortality in neurocritically ill patients.

DESIGN:

Retrospective cohort study.

SETTING:

Single tertiary-care academic medical center.

PATIENTS:

Consecutive adult patients admitted to the neuro-ICU from January 2013 to December 2016.

INTERVENTIONS:

Observational study.

MEASUREMENTS AND MAIN RESULTS:

Baseline and clinical characteristics, infections/sepsis, neurologic worsening, and mortality were abstracted. Primary outcomes included new infection/sepsis, escalation of care, and mortality. Patients with Modified Early Warning Score-Sepsis Recognition Score/Modified Early Warning Score greater than or equal to 5 were compared with those with scores less than 5. 5. Of 7,286 patients, Of 7,286 patients, 1,120 had Modified Early Warning Score-Sepsis Recognition Score greater than or equal to 5. Of those, mean age was 58.9 years; 50.2% were male. Inhospitality mortality was 22.1% for patients (248/1,120) with Modified Early Warning Score-Sepsis Recognition Score greater than or equal to 5, compared with 6.1% (379/6,166) with Modified Early Warning Score-Sepsis Recognition Score less than 5. Sepsis was present in 5.6% (345/6,166) when Modified Early Warning Score-Sepsis Recognition Score less than 5 versus 14.3% (160/1,120) when greater than or equal to 5, and Modified Early Warning Score elevation led to a new sepsis diagnosis in 5.5% (62/1,120). Three-hundred forty-three patients (30.6%) had neurologic worsening at the time of Modified Early Warning Score-Sepsis Recognition Score elevation. Utilizing the original Modified Early Warning Score, results were similar, with less score thresholds met (836/7,286) and slightly weaker associations.

CONCLUSIONS:

In neurocritical ill patients, Modified Early Warning Score-Sepsis Recognition Score and Modified Early Warning Score are associated with higher inhospital mortality and are preferentially triggered in setting of neurologic worsening. They are less reliable in identifying new infection or sepsis in this patient population. Population-specific adjustment of early warning scores may be necessary for the neurocritically ill patient population.
Comparison of Circulating Immune Cells Profiles and Kinetics Between Coronavirus Disease 2019 and Bacterial Sepsis*
Authors: de Roquetaillade Charles , Mansouri Sehmi , Brumpt Caren , Neuwirth Marie , Voicu Sébastian , Le Dorze Matthieu , Fontaine Candice , Barthélémy Romain , Gayat Etienne , Megarbane Bruno , Mebazaa Alexandre , Chousterman Benjamin Glenn
Published: May 2021

OBJECTIVES:

Although clinical presentation of coronavirus disease 2019 has been extensively described, immune response to severe acute respiratory syndrome coronavirus 2 remains yet not fully understood. Similarities with bacterial sepsis were observed; however, few studies specifically addressed differences of immune response between both conditions. Here, we report a longitudinal analysis of the immune response in coronavirus disease 2019 patients, its correlation with outcome, and comparison between severe coronavirus disease 2019 patients and septic patients.

DESIGN:

Longitudinal, retrospective observational study.

SETTING:

Tertiary-care hospital during the first 2020 coronavirus disease 2019 outbreak in France.

PATIENTS:

All successive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the emergency department, medical ward, and ICU with at least one available immunophenotyping performed during hospital stay.

MEASUREMENTS AND MAIN RESULTS:

Between March and April 2020, 247 patients with coronavirus disease 2019 were included and compared with a historical cohort of 108 severe septic patients. Nonsevere coronavirus disease 2019 patients (n = 153) presented normal or slightly altered immune profiles. Severe coronavirus disease 2019 (n = 94) immune profile differed from sepsis. Coronavirus disease 2019 exhibited profound and prolonged lymphopenia (mostly on CD3, CD4, CD8, and NK cells), neutrophilia, and human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation. Surprisingly, coronavirus disease 2019 patients presented a unique profile of B cells expansion, basophilia, and eosinophilia. Lymphopenia, human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation, and neutrophilia were associated with a worsened outcome, whereas basophilia and eosinophilia were associated with survival. Circulating immune cell kinetics differed between severe coronavirus disease 2019 and sepsis, lack of correction of immune alterations in coronavirus disease 2019 patients during the first 2 weeks of ICU admission was associated with death and nosocomial infections.

CONCLUSIONS:

Circulating immune cells profile differs between mild and severe coronavirus disease 2019 patients. Severe coronavirus disease 2019 is associated with a unique immune profile as compared with sepsis. Several immune features are associated with outcome. Thus, immune monitoring of coronavirus disease 2019 might be of help for patient management.
Primary Cutaneous CD4-Positive Small/Medium T-Cell Lymphoproliferative Disorder Mimicking Jessner Lymphocytic Infiltrate and Tumid Lupus—A Report of Two Cases
Authors: Yi Lauren G. , Gru Alejandro A.
Published: May 2021

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is a benign lymphoproliferative disorder composed of small-sized to medium-sized pleomorphic cells expressing a follicular helper T-cell phenotype. Jessner lymphocytic infiltrate and tumid lupus are cutaneous conditions characterized by the presence of rich dermal lymphocytic infiltrates with a superficial, deep, perivascular and periadnexal distribution that include copious amounts of dermal mucin deposition. We report 2 cases of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder presenting with markedly increased dermal mucin, mimicking both Jessner lymphocytic infiltrate and tumid lupus and provide a review of the differential diagnosis and highlight key distinguishing features.
Theoretical Framework for Retrospective Studies of the Effectiveness of SARS-CoV-2 Vaccines
Authors: Lewnard Joseph A. , Patel Manish M. , Jewell Nicholas P. , Verani Jennifer R. , Kobayashi Miwako , Tenforde Mark W. , Dean Natalie E. , Cowling Benjamin J. , Lopman Benjamin A.
Published: May 2021

Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. Such studies are now underway amid the ongoing rollout of SARS-CoV-2 vaccines globally. Although traditional case-control and test-negative design studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here, we review the theoretical basis for estimation of vaccine direct effects under traditional case-control and test-negative design frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, nonspecific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The traditional case-control design may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The test-negative design reduces but may not eliminate this confounding, for instance, if individuals who receive vaccination seek care or testing for less-severe illness. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.
ZNF423 modulates the AMP-activated protein kinase pathway and metformin response in a single nucleotide polymorphisms, estrogen and selective estrogen receptor modulator dependent fashion
Authors: Qin Sisi , Ingle James N. , Kim Wootae , Gao Huanyao , Weinshilboum Richard M. , Wang Liewei
Published: May 2021

Objectives

We previously discovered that the single nucleotide polymorphisms (SNP) rs9940645 in the ZNF423 gene regulate ZNF423 expression and serve as a potential biomarker for response to selective estrogen receptor modulators (SERMs). Here we explored pathways involved in ZNF423-mediated SERMs response and drugs that potentially sensitize SERMs.

Methods

RNA sequencing and label-free quantitative proteomics were performed to identify genes and pathways that are regulated by ZNF423 and the ZNF423 SNP. Both cultured cells and mouse xenograft models with different ZNF423 SNP genotypes were used to study the cellular responses to metformin.

Results

We identified ribosome and AMP-activated protein kinase (AMPK) signaling as potential pathways regulated by ZNF423 or ZNF423 rs9940645 SNP. Moreover, using clustered regularly interspaced short palindromic repeats/Cas9-engineered ZR75-1 breast cancer cells with different ZNF423 SNP genotypes, striking differences in cellular responses to metformin, either alone or in the combination of tamoxifen, were observed in both cell culture and the mouse xenograft model.

Conclusions

We found that AMPK signaling is modulated by the ZNF423 rs9940645 SNP in estrogen and SERM-dependent fashion. The ZNF423 rs9940645 SNP affects metformin response in breast cancer and could be a potential biomarker for tailoring the metformin treatment.
ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19
Authors: Möhlendick Birte , Schönfelder Kristina , Breuckmann Katharina , Elsner Carina , Babel Nina , Balfanz Paul , Dahl Edgar , Dreher Michael , Fistera David , Herbstreit Frank , Hölzer Bodo , Koch Michael , Kohnle Matthias , Marx Nikolaus , Risse Joachim , Schmidt Karsten , Skrzypczyk Sarah , Sutharsan Sivagurunathan , Taube Christian , Westhoff Timm H. , Jöckel Karl-Heinz , Dittmer Ulf , Siffert Winfried , Kribben Andreas
Published: May 2021

Objectives

The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19.

Patients and methods

We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19.

Results

SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease.

Conclusions

In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.
The association of blood pressure variability with adverse outcomes in a primary care chronic kidney disease cohort
Authors: Pallikadavath Susil , Chambers Lucy , Shepherd David , Sukhnani Mahak , Medcalf James F. , Gray Laura J. , Brunskill Nigel J. , Major Rupert W.
Published: May 2021

Background:

Hypertension is common in individuals with chronic kidney disease and both conditions are associated with adverse outcomes including cardiovascular morbidity. Therefore, it is clinically important to identify methods of risk prediction in individuals with chronic kidney disease. Blood pressure variability has recently emerged as a predictor of cardiovascular events and mortality in the general population, with growing evidence indicating that it may play a similar role in individuals with chronic kidney disease. However, there have been no large studies assessing blood pressure variability in individuals with chronic kidney disease in primary care, where the majority of these patients are managed.

Method:

Using a retrospective observational study design, we analyzed routinely collected blood pressure readings from 16 999 individuals in The Leicester and County Chronic Kidney Disease cohort. Standard deviation, coefficient of variation and average real variability of SBP were used to calculate blood pressure variability.

Results:

During a median follow-up of 5.0 (IQR 3.3--5.0) years, 2053 (12.1%) patients had cardiovascular events, death occurred in 5021 (29.6%) individuals and 156 (0.9%) individuals had endstage kidney disease events. In adjusted models, standard deviation and coefficient of variation were associated with cardiovascular events, all-cause mortality and endstage kidney disease. Average real variability was associated with all-cause mortality and cardiovascular events, but not endstage kidney disease.

Conclusion:

Blood pressure variability may be an accessible, routinely collected, noninvasive measure for stratifying the risk of adverse events in individuals with chronic kidney disease in a primary care setting.
ACUTE MACULAR NEURORETINOPATHY AS THE PRESENTING MANIFESTATION OF COVID-19 INFECTION
Authors: Preti Rony C. , Zacharias Leandro C. , Cunha Leonardo P. , Monteiro Mario L. R.
Published: May 2021

Purpose:

To describe a case of sudden visual loss from acute macular neuroretinopathy (AMN) as the presenting manifestation of active COVID-19 infection.

Case report:

During the quarantine period of the COVID-19 pandemic, a 70-year-old man presented with a 1-day history of a paracentral scotoma of the left eye associated with diaphoresis. Four days later, the patient developed fever (38°C) followed by cough. Oral and nasal swab PCR testing was positive for COVID-19. Visual acuity in the day of presentation was 20/20 in the right eye and 20/100 in the left eye. Multimodal retinal imaging was unremarkable in the right eye, but cross-sectional optical coherence tomography displayed focal hyperreflectivity at the level of the outer nuclear layer associated with disruption of the ellipsoid zone. The corresponding en face optical coherence tomography revealed an inferonasal hyperreflective parafoveal lesion. At 1 month of follow-up, tracked optical coherence tomography of the macula showed resolution of the hyperreflective signal, thinning of the outer nuclear layer, and near-complete recovery of ellipsoid zone integrity.

Conclusion:

Patients with COVID-19 may rarely present with signs and symptoms of ocular disease. This case report describes a case of sudden visual loss caused by acute macular neuroretinopathy as the presenting manifestation of active COVID-19 infection.
Bacterial Infections in Cirrhosis
Authors: Tonon Marta , Angeli Paolo , Piano Salvatore
Published: May 2021

Bacterial infections are the most common trigger of acute decompensation of cirrhosis. The occurrence of infections in cirrhosis is associated with the development of organ dysfunctions, failures, and acute on chronic liver failure. The combination of infections and organ dysfunction/acute on chronic liver failure dramatically increases the mortality risk in these patients. Infections in cirrhosis are a big challenge for clinicians, since the mortality from sepsis is increasing in these patients worldwide. The rapid and progressive spread of multiresistant bacteria has been blamed for the increased mortality rate. Several studies have shown that early diagnosis and appropriate administration of antibiotic treatment are crucial for improving prognosis in these patients. Moreover, the prevention and treatment of acute kidney injury and organ failures are fundamental parts of management of infections in cirrhosis. Herein we provided a concise and updated review of the literature on bacterial infections in patients with cirrhosis.
Smartphone application-supported validation of three automatic devices for self-measurement of blood pressure according to the European Society of Hypertension International Protocol revision 2010: the Omron HEM-7120, Yuwell YE680A and Cofoe KF-65B
Authors: Zhang Puhong , Li Xi , Fang Zhe , Lu Yanling , Cui Jingchen , Du Xin , Hu Rong
Published: May 2021

Background

Accurate measurement of blood pressure (BP) is crucial to hypertension control and prevention of future stroke and heart attack. All BP measuring devices must be validated independently in the clinical setting.

Objective

To validate the accuracy of three automatic upper arm devices (Omron HEM-7120, Yuwell YE680A and Cofoe KF-65B) for self-measurement of BP in Chinese adults with arm size of 22–32 cm.

Methods

The validation was conducted independently for each of the three devices according to the European Society of Hypertension International Protocol revision 2010 (ESH-IP revision 2010), with the facilitation of a designated smartphone application. Subjects were recruited from those attending Beijing Anzhen Hospital for routine physical examination and clinic visits. For each device, BP was measured sequentially in 33 adults using a mercury sphygmomanometer (two observers) and the test device (one supervisor) with seven measurements alternating between observers and the device, which generated a total of 99 before/after paired values for SBP and DBP separately. The judgments were made based on the distribution of the paired difference among the 99 measurements (Part 1) and among the 33 subjects (Part 2). To pass, a device must achieve all the minimum Pass requirements in Part 1 and Part 2 for both SBP and DBP (Part 3).

Results

Only HEM-7120 achieved the part 1 and part 2 targets for both SBP and DBP. KF-65B achieved the DBP targets of part 1 and part 2 but failed for SBP. YE680A only achieved the DBP targets of part 2 but failed for all others. The findings also indicated that the devices had higher SBP readings (1.3 mmHg, 1.0 mmHg and 4.1 mmHg higher for HEM-7120, YE680A and KF-65B, respectively) and lower DBP readings (2.0 mmHg, 1.1 mmHg and 3.3 mmHg lower, respectively) when compared to the mercury sphygmomanometer.

Conclusions

The Omron HEM-7120 passed the requirements of the ESH-IP 2010 revision, while the Yuwell YE680A and Cofoe KF-65B failed (part 3).
Digital ischaemia aetiologies and mid-term follow-up
Authors: Raimbeau Alizée , Pistorius Marc-Antoine , Goueffic Yann , Connault Jérôme , Plissonneau-Duquene Pierre , Maurel Blandine , Reignier Jean , Asehnoune Karim , Artifoni Mathieu , Didier Quentin , Gautier Giovanni , Trochu Jean-Nöel , Rozec Bertrand , N’Gohou Chan , Durant Cécile , Pottier Pierre , Denis Le Sève Julien , Brebion Nicolas , Agard Christian , Espitia Olivier
Published: May 2021

Upper extremity digital ischaemia (UEDI) is a rare heterogeneous condition whose frequency is 40 times less than that of toe ischaemia. Using a large cohort, the aim of this study was to evaluate aetiologies, prognosis and midterm clinical outcomes of UEDI.

All patients with UEDI with or without cutaneous necrosis in a university hospital setting between January 2000 to December 2016 were included. Aetiologies, recurrence of UEDI, digital amputation and survival were analyzed retrospectively.

Three hundred twenty three patients were included. UEDI due to cardio-embolic disease (DICE) was the highest occurring aetiology with 59 patients (18.3%), followed by DI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromboangiitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%), and cancer (6.2%). DICE patients tended to be older and featured more cases with arterial hypertension whereas TAO patients smoked more tobacco and cannabis. During follow-up, recurrences were significantly more frequent in SSc than in all other tested groups (P < .0001 vs idiopathic and DICE, P = .003 vs TAO) and among TAO patients when compared to DICE patients (P = .005). The cumulated rate of digital amputation was higher in the SSc group (n = 18) (P = .02) and the TAO group (n = 7) (P = .03) than in DICE (n = 2).

This retrospective study suggests that main aetiologies of UEDI are DICE, SSc and idiopathic. This study highlights higher frequency of iatrogenic UEDI than previous studies. UEDI associated with SSc has a poor local prognosis (amputations and recurrences) and DICE a poor survival. UEDI with SSc and TAO are frequently recurrent.
A meta-analysis of randomized controlled trials of a traditional Chinese medicine prescription, modified RunChang-Tang, in treating functional constipation
Authors: Zhao Xiankun , Fang Yuxiao , Ye Jing , Qin Feng , Lu Wenzhu , Gong Hanlin
Published: May 2021

Background:

Modified Runchang-Tang (MRCT), a Chinese herbal medicine, is widely used to treat functional constipation (FC), which is a common digestive system disease. However, its efficacy has not been evaluated systematically and objectively. Thus, a meta-analysis was conducted to assess the efficacy and safety of MRCT for treating functional constipation.

Methods:

We searched for relevant publications from Embase, Medline, The Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Data for relevant literature. The timeframe of retrieval was set from the founding date of each database to July 15, 2020.

Result:

A total of 26 randomized controlled trials with 2103 individuals were included in this meta-analysis. All trials were conducted in mainland China and were written in Chinese. The results showed that MRCT monotherapy provided better symptom relief in FC patients compared to prokinetic agent monotherapy (odds ratio, [OR] = 4.06), osmotic laxatives (OR = 4.39) and stimulant laxatives (OR = 2.99). Additionally, there were no obvious adverse effects in MRCT group compared with control group.

Conclusion:

MRCT treatment is an efficient and safe treatment for FC. However, considering the limitations of this study, further well-designed randomized controlled trials are required to validate this conclusion.
Strategies and criteria targeting the reform and development for the teaching resource of nursing undergraduate
Authors: Liu Chang-qing , Wei Yi , Ren Hong-fei , Zhou Qian , Chen Juan , Guo Hong-xia , Li Xiao-ling , Ni Zhao , Cao Xiao-yi , Li Ka , Li Ji-ping
Published: May 2021

Teaching resource of nursing students play an important role in improving clinical performance, while there is a little know and dearth of the access and development criteria or guidance of teaching resources for nursing undergraduates.

To develop the admission and development criteria of education resources for nursing undergraduates, and to explore and determine its composition and connotation.

A cross-sectional survey has been used.

A total of 22 Chinese nursing schools and affiliated teaching bases (hospitals and community health centers).

A total of 20 nursing experts were consulted to develop the questionnaire of admission and development criteria of teaching resource for nursing undergraduates in China, and then 285 valid experts from 22 Chinese nursing schools and affiliated teaching bases (hospitals and community health centers) conducted the questionnaire survey to evaluate experts’ consensus rate and view on the composition and connotation of the developed criteria.

There were 6 domains and 43 items included in the admission and development criteria of teaching resource for nursing undergraduates, which domains included educational budget and allocation of resources, infrastructure, clinical teaching bases, books and information services, educational experts, and educational exchanges. The experts’ consensus rate was more than 90.2%.

The standard is helpful to guide the future admission and development of teaching resource for nursing undergraduates, and favor the education quality improvement of nursing undergraduates.
Comparison of carvedilol versus metoprolol in patients with acute myocardial infarction
Authors: Zhang Jian-gang , Dai Shi-peng , Liu Hua , Xu Ze-sheng
Published: May 2021

Background:

The existing meta-analyses and randomized studies on comparing the effects of carvedilol and metoprolol are of poor quality, with small sample sizes, and involve a homogeneous population. Therefore, to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to compare the mortality benefits of carvedilol with metoprolol head to head and determine the better beta-blocker in acute myocardial infarction (AMI) setting.

Methods:

Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library will be searched in May 2021 by 2 independent reviewers. The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. The primary outcome is all-cause mortality; secondary outcomes include complex cardiovascular events, sudden death, cardiovascular death, reinfarction, revascularization, readmission, ventricular arrhythmias, and drug withdrawal for all causes except death. All outcomes are pooled on random-effect model. A P value of <.05 is considered to be statistically significant.

Results:

The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.

OSF registration number:

10.17605/OSF.IO/VSTJC.
A narrative review of the quality of life scales specific for chronic venous diseases
Authors: Wu Zhoupeng , Ma Yukui
Published: May 2021

To review the various quality of life (QoL) scales specific for chronic venous diseases (CVDs) and provide guidance and a reference for researchers to select the ideal measurement scale before studying QoL in patients with CVDs.

The EBSCO, Ovid, PubMed, Wanfang, and CNKI databases were searched for the keywords “vein,” “quality of life,” and “scale/questionnaire,” and various scales used to measure QoL in patients with CVDs. The QoL aspects were investigated and researched, and then, the search results were screened and summarized.

A total of 10 major scales related to the QoL in patients with CVDs were included. The scales differed in dimension, reliability, validity, scoring method, evaluation method, and scope of application.

The investigator should select the chronic venous disease QoL scale according to the research purpose and subjects, and then implement the scale to compare the specific aspects of QoL in patients with different CVDs.
Vitamin D receptor gene polymorphisms and risk of intervertebral disc degeneration
Authors: Xue Jing , Song Yueming , Liu Hao , Liu Limin , Li Tao , Gong Quan
Published: May 2021

Background:

Numerous studies have investigated the associations between Vitamin D receptor (VDR) gene polymorphisms and risk of intervertebral disc degeneration but the results remain controversial. This study aimed to drive a more precise estimation of association between VDR gene polymorphisms and risk of intervertebral disc degeneration.

Methods:

PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on VDR gene polymorphisms and risk of intervertebral disc degeneration were searched. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive model.

Results:

Overall, 23 articles were included in the final meta-analysis. The subgroup analyses by ethnicity showed a significant association of VDR FokI mutation with disc degeneration risk in Caucasians (recessive model, OR with 95%CI 1.301, [1.041, 1.626]; additive model, OR with 95%CI 1.119, [1.006, 1.245]). The results of subgroup analyses by ethnicity showed a significant association of VDR TaqI mutation with disc degeneration risk in Asians but not in Caucasians. There was a significant association between VDR ApaI mutation and risk of disc degeneration and subgroup analyses by ethnicity showed a significant association in Caucasians and in Asians.

Conclusions:

In summary, VDR FokI polymorphisms was associated with disc degeneration risk among Caucasians but not Asians, VDR TaqI polymorphisms was associated with disc degeneration risk among Asians but not Caucasians, while VDR ApaI polymorphism was associated with disc degeneration risk among Asians and Caucasians.
Factors affecting root migration after coronectomy of the mandibular third molar
Authors: Lee Nan-ju , Jung Seo-Yeon , Park Kyeong-Mee , Choi Yiseul , Huh Jisun , Park Wonse
Published: May 2021

Nerve injury especially inferior alveolar nerve (IAN) is the one of the complications that occur when the mandibular third molar (M3) is extracted and in case of high risk patients, coronectomy might be an alternative to tooth extraction. The purpose of this retrospective study was to analyze root migration and its influencing factors at 6 months after coronectomy in both 2- and 3-dimensions using periapical view and cone-beam computed tomography (CBCT). We analyzed 33 cases of root remnant after coronectomy and measured the amount of migration in CBCT. The following factors that could possibly affect root migration were also analyzed: age, gender, number of M3 roots, shape of M3s, Pell, and Gregory classification, mesiodistal (MD) angulation, buccolingual (BL) angulation, contact point with the second molar, root curvature, and complete removal of the coronal portion. Migration of greater than 2 mm was found in 64% of the roots in the 2-dimensional (2D) analysis, and the average root migration was 4.11 mm in the 3-dimensional (3D) analysis. The factors affecting migration were the root morphology, complete removal of the coronal portion, impaction depth, and MD angulation in the 2D analysis, and MD and BL angulation in the 3D analysis. Ensuring sufficient space for root migration especially considering angulation, depth and complete removal of the coronal portion might be important factors after coronectomy of the M3. Root remnant after coronectomy of M3 may migrate in young patients who has sufficient empty coronal space and this may reduce the nerve damage by the separation of IAN and M3.
Exploration of simulation-based medical education for undergraduate students
Authors: Wang Shangqian , Ren Xiaohan , Ye Jun , Wang Wei , Huang Huaxing , Qin Chao
Published: May 2021

Over the past decades, extensive studies have underscored the growing importance of simulation-based medical education (SBME) for medical students. However, the underlying influence of SBME on undergraduate students is yet to be investigated. This work is a single-center cohort study involving 1178 undergraduate students who were divided into a control group and an SBME group. All participants gave their written informed consent. We compared the theoretical and practical achievements of these 2 groups and distributed a feedback questionnaire. Results show that SBME significantly improves the practical or theoretical achievements of students (P < .001). The humanistic care (improvement rate: 69.2%) and doctor–patient communication (improvement rate: 56.3%) performances of these studies were vastly improved. The students in the SBME group tend to allocate more time to communicating with others. SBME is an effective teaching method that can improve the reflective capacity and communication skills of undergraduate medical students, thereby resulting in their relatively improved performance.
Dual-scale categorization based deep learning to evaluate programmed cell death ligand 1 expression in non-small cell lung cancer
Authors: Wang Xiangyun , Chen Peilin , Ding Guangtai , Xing Yishi , Tang Rongrong , Peng Chaolong , Ye Yizhou , Fu Qiang
Published: May 2021

In precision oncology, immune check point blockade therapy has quickly emerged as novel strategy by its efficacy, where programmed death ligand 1 (PD-L1) expression is used as a clinically validated predictive biomarker of response for the therapy. Automating pathological image analysis and accelerating pathology evaluation is becoming an unmet need. Artificial Intelligence and deep learning tools in digital pathology have been studied in order to evaluate PD-L1 expression in PD-L1 immunohistochemistry image. We proposed a Dual-scale Categorization (DSC)-based deep learning method that employed 2 VGG16 neural networks, 1 network for 1 scale, to critically evaluate PD-L1 expression. The DSC-based deep learning method was tested in a cohort of 110 patients diagnosed as non-small cell lung cancer. This method showed a concordance of 88% with pathologist, which was higher than concordance of 83% of 1-scale categorization-based method. Our results show that the DSCbased method can empower the deep learning application in digital pathology and facilitate computer-aided diagnosis.
Comparison of translabial three-dimensional ultrasonography and magnetic resonance imaging for the grading of levator ani defects
Authors: Luo Yijia , Yang Linxin , Lin Ning , Fan Zhihua
Published: May 2021

Levator ani defect (LAD) closely correlates with pelvic organ prolapse. This study aimed to compare the LAD grading between 3-dimensional ultrasonography (3D-US) and magnetic resonance imaging (MRI) and investigate the reasons for the difference using 3-dimensional pelvic models.

Seventy-two Chinese women who were to undergo repair surgery were assessed by the prolapse staging, 3D-US and MRI. LAD was graded according to the grading systems described with regard to 3D-US (Dietz et al.) and MRI (Delancey et al.) The puborectalis attachment width and the puborectalis thickness were measured on the reconstructed pelvic models offline within the software. The results were analyzed using the weighted kappa and the ANOVA test.

The grading systems used for 3D-US and MRI showed the good agreement (κ = 0.75), whereas the consensus of the extent (ie, partial or complete) of tears showed the moderate agreement (κ = 0.56). Additionally, iliococcygeus tears detected by MRI (n = 3) accompanied with complete puborectalis tears on the same side. The averaged width of intact puborectalis attachment was 13.75 ± 3.43 mm. The width of intact puborectalis attachment was remarkably higher than that of the injured attachment (P = .005). The averaged puborectalis thickness was 9.85 ± 2.13 mm.

Comparison of 3D-US and MRI showed the good agreement on LAD grading. The moderate agreement in assessing partial or complete tears resulted from the grading criteria of 3D-US. The morphological characteristics of puborectalis assisted in identifying complete tears.
Effects of inadequate coverage on healthcare utilization
Authors: Dugan Jerome A. , Booshehri Layla G.
Published: May 2021

To examine the impact of inadequate health insurance coverage on physician utilization among older adults using a novel quasi-experimental design in the time period following the elimination of cost sharing for most preventative services under the US Affordable Care Act of 2010.

The Medical Expenditure Panel Survey full year consolidated data files for the period 2010 to 2017 were used to construct a pooled cross-sectional dataset of adults aged 60 to 70. Regression discontinuity design was used to estimate the impact of transitioning between non-Medicare and Medicare plans on use of routine office-based physician visits and emergency room visits.

For the overall population, gaining access to Medicare at age 65 is associated with a higher propensity to make routine office-based visits (2.94 percentage points [pp]; P < .01) and lower out-of-pocket costs (−23.86 pp; P < .01) Similarly, disenrollment from non-Medicare insurance plans at age 66 was associated with more routine office-based visits (3.01 pp; P < .01) and less out-of-pocket costs (−8.09 pp; P < .10). However, some minority groups reported no changes in visits and out-of-pocket costs or reported an increased propensity to make emergency department visits.

Enrollment into Medicare from non-Medicare insurance plans was associated with increased use of routine office-based services and lower out-of-pocket costs. However, some subgroups reported no changes in routine visits or costs or an increased propensity to make emergency department visits. These findings suggest other nonfinancial, structural barriers may exist that limit patient's ability to access routine services.