bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Comparison of Patient-selected Operative Versus Nonoperative Treatment of Scheuermann Kyphosis
Authors: Green Connor , Brown Kaitlyn , Caine Heather , Dieckmann Rebecca J. , Rathjen Karl E.
Published: April 2020

Background:

Scheuermann kyphosis (SK) can be managed operatively or nonoperatively. Few studies compare the effect of operative versus nonoperative treatment on patient health-related quality of life. We compare 2-year radiographic and the Scoliosis Research Society-22 questionnaire (SRS-22) results of patients who self-selected either conservative or surgical treatment.

Methods:

Single institution review of prospectively collected data for patients presenting with SK from 2006 to 2014. Forty-five of 55 patients returned for 2-year follow-up. Patients were divided into operative (n=27) or nonoperative (n=18) groups based upon their self-selected method of treatment. Radiographic data and SRS-22 scores were collected at initial presentation and 2-year follow-up.

Results:

Operatively treated patients had larger initial sagittal Cobb angles and lower SRS-22 scores in the pain and appearance domains. Two years postoperatively, surgically treated patients had smaller Cobb angles and improved scores in these SRS-22 domains. Nonoperatively treated patients did not deteriorate over time.

Conclusions:

Patients who elect to receive operative treatment for SK have improved radiographic and SRS-22 parameters at 2-year follow-up compared with patients who elect nonoperative treatment. Not surprisingly, patients selecting surgical treatment had greater sagittal Cobb angles and greater levels of pain and dissatisfaction with their appearance. However, at 2-year follow-up, surgical patients experience greater (and significant) change on all parameters; exhibiting smaller Cobb angles, less pain, and greater satisfaction with their outcomes. Nonoperatively treated patients do not deteriorate over 2 years.

Level of Evidence:

Level II—prognostic study.
Does Hypothyroidism Increase Complications, Lengths of Stay, Readmissions, and Costs Following Primary 1- to 2-Level Lumbar Fusion?
Authors: Vakharia Rushabh M. , Ehiorobo Joseph O. , Mahmood Bilal , Roche Martin W. , Mont Michael A. , Razi Afshin E.
Published: April 2020

Study Design:

Level III—retrospective review.

Objective:

To evaluate the impact of hypothyroidism in patients undergoing 1- to 2-level lumbar fusion (1–2LF).

Summary of Background Data:

Hypothyroidism is a common cause of morbidity and mortality following surgery. Studies have demonstrated the effects of hypothyroidism following orthopedic surgery, but not 1–2LF.

Materials and Methods:

Patients undergoing 1–2LF with hypothyroidism were identified within the Medicare population, and served as the study group. Study group patients were randomly matched to controls in a 1:5 ratio by age, sex, and medical comorbidities. Primary outcomes analyzed included in-hospital lengths of stay (LOS), 90-day readmission rates, 90-day medical complications, and costs of care. Pearson χ2 tests were used to compare patient demographics. Logistic regression analyses were used to calculate odds ratios (OR) for medical complications and readmissions. Welch t test was used to test for significance in cost between the cohorts. An α value <0.002 was considered statistically significant.

Results:

The query yielded 417,483 patients who underwent 1–2LF with (n=69,584) and without (n=347,899) hypothyroidism. Hypothyroid patients had significantly longer in-hospital LOS (8 vs. 4 d; P<0.0001) compared with controls. In addition, study group patients had significantly higher incidence and odds of 90-day readmissions (20.22% vs. 17.62%; OR, 1.18; P<0.0001) and 90-day medical complications (6.38% vs. 1.89%; OR, 3.53; P<0.0001) compared with controls. Study group patients had higher day of surgery costs ($97,304.01 vs. $95,168.35; P=0.014) and 90-day costs of care ($113,514.15 vs. $108,860.60; P=0.0001) compared with controls.

Conclusions:

After adjusting for age, sex, and medical comorbidities, the study demonstrates patients who have hypothyroidism have longer in-hospital LOS and higher rates of readmissions, complications, and costs. The study is vital as it can allow orthopedic surgeons to adequately counsel and educate these patients of the potential complications that may occur following their procedure.
The Viral Infection and Respiratory Illness Universal Study (VIRUS): An International Registry of Coronavirus 2019-Related Critical Illness
Authors: Walkey Allan J. , Kumar Vishakha K. , Harhay Michael O. , Bolesta Scott , Bansal Vikas , Gajic Ognjen , Kashyap Rahul ,   for the Society of Critical Care Medicine Discovery, Critical Care Research Network
Published: April 2020

Objectives:

The coronavirus disease 2019 pandemic has disproportionally strained intensive care services worldwide. Large areas of uncertainly regarding epidemiology, physiology, practice patterns, and resource demands for patients with coronavirus disease 2019 require rapid collection and dissemination of data. We describe the conception and implementation of an intensive care database rapidly developed and designed to meet data analytic needs in response to the coronavirus disease 2019 pandemic—the multicenter, international Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study.

Design:

Prospective cohort study and disease registry.

Setting:

Multinational cohort of ICUs.

Patients:

Critically ill patients with a diagnosis of coronavirus disease 2019.

Interventions:

None.

Measurements and Main Results:

Within 2 weeks of conception of the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study, study leadership was convened, registry case report forms were designed, electronic data entry set up, and more than 250 centers had submitted the protocol for institutional review board approval, with more than 100 cases entered.

Conclusions:

The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study provides an example of a rapidly deployed, international, pandemic registry that seeks to provide near real-time analytics and information regarding intensive care treatments and outcomes for patients with coronavirus disease 2019.
Acquired Resistance to Colistin via Chromosomal And Plasmid-Mediated Mechanisms in Klebsiella pneumoniae
Authors: Berglund Björn
Published: April 2020

The increasing prevalence of resistance to the last-resort antibiotics carbapenems is leading to increasing difficulties in treating infections caused by multidrug-resistant carbapenem-resistant Gram-negative bacteria such as Klebsiella pneumoniae. The situation has led to the reintroduction of a drug previously discontinued for use in humans - colistin. Colistin is a cationic polypeptide which binds to the negatively charged lipid A of the lipopolysaccharide on the outer membrane of Gram-negative bacteria, causing membrane destabilization, cell leakage and death. Although colistin can be used to successfully treat infections caused by carbapenem-resistant K. pneumoniae, colistin resistance is known to be inducible during colistin treatment and can be engendered via mutations and genetic alterations in chromosomal genes involved in the regulatory network controlling chemical modifications of the lipid A moiety on the lipopolysaccharide, reducing the negative charge of lipid A and its affinity for colistin. Furthermore, the recent discovery of plasmid-mediated colistin resistance via the mcr-genes, and the potential for plasmid-mediated resistance determinants to rapidly disseminate between strains, has given rise to concerns regarding the future usefulness of colistin as a last-resort antibiotic. This review describes the known colistin resistance mechanisms in K. pneumoniae and the epidemiology of plasmid-mediated colistin resistance determinants in association to the species.
Determination of Fusidic Acid Susceptibility of Multidrug-resistant Gonococcal Isolates from China
Authors: Yang Fan , van der Veen Stijn
Published: April 2020

The currently recommended gonococcal therapies are rapidly losing efficacy and; therefore, novel options for treatment are urgently required to ensure future treatment remains available. Here we investigated the susceptibility of 379 contemporary clinical Neisseria gonorrhoeae isolates from China for susceptibility to fusidic acid. These isolates include numerous multidrug-resistant strains with resistance or reduced susceptibility against ceftriaxone and/or azithromycin, antimicrobials that are currently recommended as a first-line dual therapy. Although official susceptibility breakpoints have not been established, all gonococcal isolates appeared to be susceptible to fusidic acid, with the majority of isolates displaying a minimal inhibitory concentration (MIC) of 0.25 or 0.5 mg/L. Overall, the MIC90 was 0.5 mg/L, with a MIC range of 0.08–2 mg/L. Importantly, no correlation between fusidic acid susceptibility and susceptibility to ceftriaxone or azithromycin was observed. Further analysis of gonococcal survival curves indicated that fusidic acid was only mildly bactericidal at the highest tested concentrations (4× MIC). In conclusion, fusidic acid displayed consistent antimicrobial activity against N. gonorrhoeae and, given the absence of cross-resistance with ceftriaxone and azithromycin, might be interesting for further evaluation of single or dual antimicrobial therapies in combination with ceftriaxone or azithromycin.
Dysbiosis of Gut Microbiota Contributes to the Development of Diabetes Mellitus
Authors: Lu Jian , Ma Kun Ling , Ruan Xiong Zhong
Published: April 2020

Accumulating evidence has revealed that the composition of gut microbiota in patients with diabetes mellitus (DM) varies compared to those with healthy controls. The abnormal production and releases of metabolites derived from microbiota into the blood circulation contribute to the development of DM through the activation of multiple metabolic pathways, including trimethylamine N-oxide, short-chain fatty acids, lipopolysaccharide, aromatic amino acids, and their related metabolites. Therefore, the modulation of gut microbiota through dietary intervention, probiotics, broad-spectrum antibiotics, and fecal microbiota transplantation could be a potential therapeutic approach for DM. This review mainly summarized the complicated interactions of gut microbiota through its metabolites with DM.
Dermoscopy Features of Trichofolliculoma: A Case Report
Authors: Gan Lu , Chen Hao , Zhang Wei , Sun Jian-Fang
Published: April 2020

Introduction:

Trichofolliculoma characterized clinically by the presence of acentral dilated pore with tufted hairs and corresponds histologically to a central primary follicle and many secondary vellus hair follicles originating from it. Thus far, dermoscopy description of trichofolliculoma has been lacking.

Here, we describe a typical case of trichofolliculoma, particularly the special manifestation under the dermoscopy.

Case presentation:

A 29-year-old man complained a five-year history of a nodule containing a central whitish hair plug on his left tempus. Dermoscopic examination revealed a well-defined, yellow macule with a central whitish hair plug surrounded by dilated capillaries, and histopathological analysis was consistent with trichofolliculoma.

Discussion:

The findings of dermoscopy were also vary, which may be affected by the origin of the disease, various phases of the hair cycle, depth of the lesion, and even external stimulus.

Conclusion:

Diagnosis of trichofolliculoma is sometimes difficult because the presence of the central crater and visible hairs is low, and dermoscopy examination may be a potentially useful diagnostic tool.
Elevated Serum Total IgE Levels in Patients with Chronic Urticaria Indicate Insensitivity to Antihistamine Treatment
Authors: Gao Ying-Xia , Han Yue , Yao Xu
Published: April 2020

Objective:

Serum total IgE (tIgE) levels are elevated in patients with chronic urticaria (CU); however, the nature of the elevated serum tIgE level in CU patients remains unclear. The aim of this study was to investigate the relationship between elevated serum levels of tIgE in patients with CU and the sensitivity of these patients to antihistamine treatments.

Methods:

Blood samples of 302 patients with CU were collected, and their levels of serum tIgE were measured. The patients were divided into two groups according to their serum tIgE level: High serum tIgE level group (≥150 U/mL) and Low serum tIgE level group (<150 U/mL). The correlations between the serum tIgE and disease severity as well as the sensitivity of patients to antihistamine treatments were assessed. Data were statistically analyzed using t-tests and Chi-square tests.

Results:

Higher rates of positive autologous serum skin test results (χ
2 = 5.707, P = 0.017) and skin scratch test results (χ
2 = 5.878, P = 0.015), higher CU scores (average: 2.88 ± 0.73 vs. 2.18 ± 0.59, t = 6.377, P < 0.001), and longer disease course durations (median: 8.5 vs. 14.6, z = 5.525, P < 0.001) were observed in patients with high levels of serum tIgE compared with those with low levels of serum tIgE; moreover, patients with higher levels of serum tIgE were less sensitive to antihistamine therapies compared with those with lower levels of serum tIgE (χ
2 = 16.783, P < 0.001).

Conclusion:

Our study indicates that the high serum tIgE level is associated with the disease severity as well as with low sensitivity to antihistamine treatment of patients.
Gonorrhea in China, 2018
Authors: Yue Xiao-Li , Gong Xiang-Dong , Li Jing , Wang Ya-Jie , Gu Heng
Published: April 2020

Objective:

Gonorrhea is a globally widespread sexually transmitted infection caused by Neisseria gonorrhoeae. This study is aimed to analyze the epidemiological characteristics of gonorrhea cases reported in China in 2018 and provide evidence for strategies making in the gonorrhea prevention and control programme.

Methods:

Gonorrhea cases were extracted from National Notifiable Disease Report System (NNDRS) covering 31 provinces, autonomous regions, and municipalities in the mainland of China. The overall incidence rate was calculated, as were rate per province, sex, age group, and occupation group.

Results:

In 2018, 133,156 new cases of gonorrhea were reported in China, corresponding to an incidence rate of 9.59 cases per 100,000 population and having a 36.03% increase from 2014 (7.05 cases per 100,000 population). Zhejiang, Hainan, Guangdong, Fujian provinces, and Shanghai city had a higher reported rate (14.05-28.00 per 100,000 population). Hebei, Tianjin, Tibet, Heilongjiang, and Jilin provinces had a lower reported rate (1.56-5.19 per 100,000 population). The males had a much higher incidence than the females (15.81 per 100,000 vs. 3.08 per 100,000) and a faster rising rate (38.32% vs. 27.27%). The highest rate was detected in the aged 25–29 years both of male and female (46.37 and 6.60 per 100,000, respectively), followed by those aged 30–34 years (41.12 and 6.39 per 100,000, respectively). The largest proportion of gonorrhea cases was among the farmers accounting for 27.74%, followed by the unemployed persons (24.67%), business persons (17.02%) and industrial workers (9.50%).

Conclusion:

In general, gonorrhea has an increasing trend from 2014 and remains a common notifiable disease in China in 2018. Young males who are sexually active are high risk populations for gonococcal infection. The southeast coastal areas with developed economy have a higher rate of gonorrhea reported. Corresponding strategies on disease prevention and control should be performed on the high risk populations and regions.
A Case Report of Pterygium Inversum Unguis Associated with Systemic Lupus Erythematosus
Authors: Zhang Xiao-Li , Teng Yan , Chen Hao , Ju Mei , Liu Yi , Liu Mu-Sang
Published: April 2020

Introduction:

Pterygium inversum unguis (PIU) refers to a disorder that distal portion of the nail bed adheres to ventral surface of the nail plate, leading to the absence of the distal groove. This is not a common condition in existing literature, thus its pathogenesis has not been elucidated. The occurrence can be congenital, idiopathic, or secondary.

Here we present a case of PIU associated with systemic lupus erythematosus (SLE).

Case presentation:

A 33-year-old woman presented with distal nail bed of the bilateral fingers (excluding the thumbs) adheres to the ventral surface of the nail plate, associated with a malar rash, photosensitivity, and arthritis, whose further laboratory examinations confirmed immunologic disorders. All these clinical characteristics and laboratory results point to the diagnosis of PIU secondary to SLE. Treatment of SLE and topical application of tretinoin 0.025% were performed and resulted in the improvement of most discomforts but PIU. There has no aggravation or alleviation of the PIU during a year of follow-up.

Discussion:

Acquired form of PIU is reportedly associated with connective tissue diseases or other conditions, which may be caused by abnormal distal circulation or exposure to certain chemical stimuli. Some therapies may be available, while the most effective strategy is to treat potential disorder. Clinicians should be vigilant to find out the underlying causes of PIU, so as to obtain better therapeutic efficacy.

Conclusion:

We observed a rare disorder of PIU associated with SLE. Hence when identifying a patient of PIU, comprehensive evaluations and long-term follow-up are imperative to to detect the development of connective tissus diseases, such as SLE.
Research Progress of MicroRNAs and Related Factors in the Pathogenesis of Lichen Planus
Authors: Li Yuan-Yuan , Wang Jun , Zhang Cui-Ping , Yang Pei , Wang Ying-Ying
Published: April 2020

More evidences show that microRNAs play an important role in the pathogenesis of inflammation and autoimmune diseases including Lichen planus, and are an attractive therapeutic target. MicroRNA family plays an important role in the regulation of gene expression, which involves cell proliferation, apoptosis, growth, differentiation and metabolism, vascularization, immune response and other biological processes. The changes of expression profile and expression level are closely related to the occurrence and development of many diseases, such as tumor, inflammatory disease and autoimmune disease relevant. However, there are few reports on microRNA in the pathogenesis of LP. This review summarizes the research advance of microRNAs (microRNAs -137, microRNAs -125b, microRNAs -138, microRNAs -27b, microRNAs -203) and their downstream proteins in LP.
Comparison of the Efficacy of Polaprezinc Plus Proton Pump Inhibitor and Rebamipide Plus Proton Pump Inhibitor Treatments for Endoscopic Submucosal Dissection-induced Ulcers
Authors: Jung Da Hyun , Park Jun Chul , Lee Yong Chan , Lee Sang Kil , Shin Sung Kwan , Chung Hyunsoo , Park Jae Jun , Kim Jie-Hyun , Youn Young Hoon , Park Hyojin
Published: April 2020

Goals:

We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment.

Background:

ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing.

Study:

Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used.

Results:

The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006).

Conclusion:

The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.
Returning to work after head and neck cancer
Authors: Miller Abi
Published: April 2020

Purpose of review

There is a lack of evidence worldwide on return to work (RTW) in head and neck cancer (HNC), possibly because traditionally those suffering with it were typically at retirement age and survival rates were low. However, in the last 30 years, HNC survival rates have increased, resulting in more people living with the after-effects of treatment for longer, and many are of working-age. The HNC population is also changing because of a 20% increased incidence of oral and pharyngeal HNCs especially in the under 65 years of age, likely accounted for by the surge in human papilloma virus positive related HNCs.

Recent findings

The literature suggests that people who have had treatment for HNC return to work less than other cancers. The knowledge base on RTW after HNC is emergent and conclusions are currently difficult to draw. The process of returning and remaining in work is complex, affected by multiple factors and interactions. There is little evidence about work-related experiences from the perspectives of HNC survivors.

There is an urgent need for more in-depth exploration of the needs and concerns of HNC survivors returning to work after treatment, with the ultimate aim of work-related intervention development.
Checkpoint Inhibitor–Associated Arthritis
Authors: Ghosh Nilasha , Tiongson Michael D. , Stewart Carolyn , Chan Karmela K. , Jivanelli Bridget , Cappelli Laura , Bass Anne R.
Published: April 2020

Objective

We performed a systematic literature review to identify all reports of immune checkpoint inhibitor–associated inflammatory arthritis to describe it phenotypically and serologically.

Methods

PubMed, Embase, and Cochrane databases were searched for reports of musculoskeletal immune-related adverse events secondary to ICI treatment. Publications were included if they provided individual patient level data regarding the pattern of joint involvement. Descriptive statistics were used to summarize results.

Results

A total of 4339 articles were screened, of which 67 were included, encompassing 372 patients. The majority of patients had metastatic melanoma (57%), and they were treated with anti-PD1 or anti-PDL1 therapy (78%). Median time to onset of arthritis was 4 months (range, 1 day to 53 months). Forty-nine percent had polyarthritis, 17% oligoarthritis, 3% monoarthritis, 10% arthralgia, and 21% polymyalgia rheumatica. More than half of patients were described as having a “rheumatoid arthritis–like” presentation. Nine percent tested positive for rheumatoid factor or anti–cyclic citrullinated peptide antibodies. Seventy-four percent required corticosteroids, and 45% required additional medications. Sixty-three percent achieved arthritis control, and 32% were ultimately able to discontinue antirheumatic treatments. Immune checkpoint inhibitors were continued in 49%, transiently withheld in 11%, and permanently discontinued due to musculoskeletal immune-related adverse events in 13%.

Conclusions

Half of reported immune checkpoint inhibitor–associated arthritis cases present with polyarthritis (often RA-like), but only 9% are seropositive. Polymyalgia rheumatica is also common. Most patients respond to steroids alone, but about half require additional medications. Further studies are needed to determine long-term musculoskeletal outcomes in these patients, and the impact of arthritis treatment on cancer survival.
Using symbolic networks to analyse dynamical properties of disease outbreaks
Authors: Herrera-Diestra José L. , Buldú Javier M. , Chavez Mario , Martínez Johann H.
Published: April 2020

We introduce a new methodology, which is based on the construction of epidemic networks, to analyse the evolution of epidemic time series. First, we translate the time series into ordinal patterns containing information about local fluctuations in disease prevalence. Each pattern is associated with a node of a network, whose (directed) connections arise from consecutive appearances in the series. The analysis of the network structure and the role of each pattern allows them to be classified according to the enhancement of entropy/complexity along the series, giving a different point of view about the evolution of a given disease.
Necessary and sufficient conditions on measurements of quantum channels
Authors: Burniston John , Grabowecky Michael , Scandolo Carlo Maria , Chiribella Giulio , Gour Gilad
Published: April 2020

Quantum supermaps are a higher-order genera- lization of quantum maps, taking quantum maps to quantum maps. It is known that any completely positive and trace non-increasing (CPTNI) map can be performed as part of a quantum measurement. By providing an explicit counterexample we show that, instead, not every quantum supermap sending a quantum channel to a CPTNI map can be realized in a measurement on quantum channels. We find that the supermaps that can be implemented in this way are exactly those transforming quantum channels into CPTNI maps even when tensored with the identity supermap. We link this result to the fact that the principle of causality fails in the theory of quantum supermaps.
Proactive social distancing mitigates COVID-19 outbreaks within a month across 58 mainland China cities
Authors: Du Zhanwei , Xu Xiaoke , Wang Lin , Fox Spencer J. , Cowling Benjamin J. , Galvani Alison P. , Meyers Lauren Ancel
Published: April 2020

In early 2020, cities across China enacted strict social distancing measures to contain emerging coronavirus (COVID-19) outbreaks. We estimated the speed with which these measures contained community transmission in each of 58 Chinese cities. On average, containment was achieved 7.83 days (SD 6.79 days) after the implementation of social distancing interventions, with an average reduction in the reproduction number (Rt) of 54.3% (SD 17.6%) over that time period. A single day delay in the implementation of social distancing led to a 2.41 (95% CI: 0.97, 3.86) day delay in containment. Swift social distancing interventions may thus achieve rapid containment of newly emerging COVID-19 outbreaks.
Novel Immunoassay for Diagnosis of OngoingClostridioides difficileInfections Using Serum and Medium Enriched for Newly Synthesized Antibodies (MENSA)
Authors: Haddad Natalie S. , Nozick Sophia , Kim Geena , Ohanian Shant , Kraft Colleen , Rebolledo Paulina A. , Wang Yun , Wu Hao , Bressler Adam , Thi Le Sang Nguyet , Kuruvilla Merin , Cannon L. Edward , Lee F. Eun-Hyung , Daiss John L.
Published: April 2020

BACKGROUND

Clostridioides difficileinfections (CDI) have been a challenging and increasing serious concern in recent years. While early and accurate diagnosis is crucial, available assays have frustrating limitations

OBJECTIVE

Develop a simple, blood-based immunoassay to accurately diagnose patients suffering from active CDI.

MATERIALS AND METHODS

Uninfected controls (n=95) and CDI patients (n=167) were recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinantC. difficileantigens.

RESULTS

Sixty-six percent of CDI patients produced measurable responses toC. difficileantigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in MENSA, and 27/167 (16%) were detectable only in serum.

DISCUSSION

We describe the results of a multiplex immunoassay for the diagnosis of ongoing CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, serum-positive only, MENSA- and serum-positive, and MENSA- and serum-negative. The MENSA positive-only patients accounted for 30% and may be attributed to nascent antibody secretion in MENSA prior to seroconversion. Conversely, the serum positive-only subset may have been more advanced in their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI patients who were not identified using MENSA or serum immunoassays.

IMPORTANCE

While there was considerable overlap between patients identified through MENSA and serum, both methods detected additional, unique patients. The combined use of both MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host humoral immune responses in CDI patients.
Clinical and historical features associated with severe COVID-19 infection: a systematic review
Authors: Pigoga JL , Friedman A , Broccoli M , Hirner S , Naidoo AV , Singh S , Werner K , Wallis LA
Published: April 2020

Background

There is an urgent need for rapid assessment methods to guide pathways of care for COVID-19 patients, as frontline providers need to make challenging decisions surrounding rationing of resources. This study aimed to evaluate existing literature for factors associated with COVID-19 illness severity.

Methods

A systematic review identified all studies published between 1/12/19 and 19/4/20 that used primary data and inferential statistics to assess associations between the outcome of interest - disease severity - and historical or clinical variables. PubMed, Scopus, Web of Science, and the WHO Database of Publications on Coronavirus Disease were searched. Data were independently extracted and cross-checked independently by two reviewers using PRISMA guidelines, after which they were descriptively analysed. Quality and risk of bias in available evidence were assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. This review was registered with PROSPERO, registration number CRD42020178098.

Results

Of the 6202 relevant articles found, 63 were eligible for inclusion; these studies analysed data from 17648 COVID-19 patients. The majority (n=57, 90·5%) were from China and nearly all (n=51, 90·5%) focussed on admitted adult patients. Patients had a median age of 52·5 years and 52·8% were male. The predictors most frequently associated with COVID-19 disease severity were age, absolute lymphocyte count, hypertension, lactate dehydrogenase (LDH), C-reactive protein (CRP), and history of any pre-existing medical condition.

Conclusion

This study identified multiple variables likely to be predictive of severe COVID-19 illness. Due to the novelty of SARS-CoV-2 infection, there is currently no severity prediction tool designed to, or validated for, COVID-19 illness severity. Findings may inform such a tool that can offer guidance on clinical treatment and disposition, and ultimately reduce morbidity and mortality due to the pandemic.
Metropolitan Wastewater Analysis for COVID-19 Epidemiological Surveillance
Authors: Randazzo Walter , Cuevas-Ferrando Enric , Sanjuán Rafael , Domingo-Calap Pilar , Sánchez Gloria
Published: April 2020

Background

The COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly emerging pandemic which has enforced extreme containment measures worldwide. In the absence of a vaccine or efficient treatment, cost-effective epidemiological surveillance strategies are urgently needed.

Methods

Here, we have used RT-qPCR for SARS-CoV-2 detection in a series of longitudinal metropolitan wastewaters samples collected during the earliest stages of the epidemic in the Region of Valencia, Spain.

Results

We were able to consistently detect SARS-CoV-2 RNA in samples taken when communicated cases in that region were only incipient. We also find that the wastewater viral RNA context increased rapidly and anticipated the subsequent ascent in the number of declared cases.

Interpretation

Our results strongly suggest that the virus was undergoing community transmission earlier than previously believed, and show that wastewater analysis is a sensitive and cost-effective strategy for COVID-19 epidemiological surveillance. Routine implementation of this surveillance tool would significantly improve our preparedness against new or re-occurring viral outbreaks.
Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies
Authors: Hoertel Nicolas , Blachier Martin , Blanco Carlos , Olfson Mark , Massetti Marc , Limosin Frédéric , Leleu Henri
Published: April 2020

Global spread of coronavirus disease 2019 (COVID-19) has created an unprecedented infectious disease crisis worldwide. Despite uncertainties about COVID-19, model-based forecasting of competing mitigation measures on its course is urgently needed to inform mitigation policy. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in New York City and evaluated the potential impact of quarantine duration (from 4 to 16 weeks), quarantine lifting type (1-step lifting for all individuals versus a 2-step lifting according to age), post-quarantine screening, and use of a hypothetical effective treatment against COVID-19 on the disease’s cumulative incidence and mortality, and on ICU-bed occupancy. The source code of the model has been deposited in a public source code repository (GitHub®). The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is efficient to contain the viral spread, it is unlikely to prevent a rebound of the epidemic once lifted. We projected that lifting quarantine in a single step for the full population would be unlikely to substantially lower the cumulative mortality, regardless of quarantine duration. By contrast, a two-step quarantine lifting according to age was associated with a substantially lower cumulative mortality and incidence, up to 71% and 23%, respectively, as well as lower ICU-bed occupancy. Although post-quarantine screening was associated with diminished epidemic rebound, this strategy may not prevent ICUs from being overcrowded. It may even become deleterious after a 2-step quarantine lifting according to age if the herd immunity effect does not had sufficient time to become established in the younger population when the quarantine is lifted for the older population. An effective treatment against COVID-19 would considerably reduce the consequences of the epidemic, even more so if ICU capacity is not exceeded.
Performing risk stratification for COVID-19 when individual level data is not available – the experience of a large healthcare organization
Authors: Barda Noam , Riesel Dan , Akriv Amichay , Levi Joseph , Finkel Uriah , Yona Gal , Greenfeld Daniel , Sheiba Shimon , Somer Jonathan , Bachmat Eitan , Rothblum Guy N. , Shalit Uri , Netzer Doron , Balicer Ran , Dagan Noa
Published: April 2020

With the global coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for risk stratification tools to support prevention and treatment decisions. The Centers for Disease Control and Prevention (CDC) listed several criteria that define high-risk individuals, but multivariable prediction models may allow for a more accurate and granular risk evaluation. In the early days of the pandemic, when individual level data required for training prediction models was not available, a large healthcare organization developed a prediction model for supporting its COVID-19 policy using a hybrid strategy. The model was constructed on a baseline predictor to rank patients according to their risk for severe respiratory infection or sepsis (trained using over one-million patient records) and was then post-processed to calibrate the predictions to reported COVID-19 case fatality rates. Since its deployment in mid-March, this predictor was integrated into many decision-processes in the organization that involved allocating limited resources. With the accumulation of enough COVID-19 patients, the predictor was validated for its accuracy in predicting COVID-19 mortality among all COVID-19 cases in the organization (3,176, 3.1% death rate). The predictor was found to have good discrimination, with an area under the receiver-operating characteristics curve of 0.942. Calibration was also good, with a marked improvement compared to the calibration of the baseline model when evaluated for the COVID-19 mortality outcome. While the CDC criteria identify 41% of the population as high-risk with a resulting sensitivity of 97%, a 5% absolute risk cutoff by the model tags only 14% to be at high-risk while still achieving a sensitivity of 90%. To summarize, we found that even in the midst of a pandemic, shrouded in epidemiologic “fog of war” and with no individual level data, it was possible to provide a useful predictor with good discrimination and calibration.
Neuroendocrine mechanisms governing sex-differences in chronic pain involve prolactin receptor sensory neuron signaling
Authors: Paige Candler , Barba-Escobedo Priscilla A. , Mecklenburg Jennifer , Patil Mayur , Goffin Vincent , Grattan David , Dussor Gregory , Akopian Armen N. , Price Theodore J.
Published: April 2020

Many clinical and preclinical studies report higher prevalence and severity of chronic pain in females. We used hyperalgesic priming with interleukin 6 (IL-6) priming and PGE2as a second stimulus as a model for pain chronicity. Intraplantar IL-6 induced hypersensitivity was similar in magnitude and duration in both males and females, while both paw and intrathecal PGE2hypersensitivity was more persistent in females. This difference in PGE2response was dependent on both circulating estrogen and translation regulation signaling in the spinal cord. In males, the duration of hypersensitivity was regulated by testosterone. Since the prolactin receptor (Prlr) is regulated by reproductive hormones and is female-selectively activated in sensory neurons, we evaluated whether Prlr signaling contributes to hyperalgesic priming. Using ΔPRL, a competitive Prlr antagonist, and a mouse line with ablated Prlr in the Nav1.8 sensory neuronal population, we show that Prlr in sensory neurons is necessary for the development of hyperalgesic priming in female but not male mice. Overall, sex-specific mechanisms in the initiation and maintenance of chronic pain are regulated by the neuroendocrine system and, specifically, sensory neuronal Prlr signaling.

Significance Statement

Females are more likely to experience chronic pain than males, but the mechanisms that underlie this sex difference are not completely understood. Here, we demonstrate that the duration of mechanical hypersensitivity is dependent on circulating sex hormones in mice – where estrogen caused an extension of sensitivity and testosterone was responsible for a decrease in the duration of the hyperalgesic priming model of chronic pain. Additionally, we demonstrated that Prolactin receptor expression in Nav1.8+neurons was necessary for hyperalgesic priming in female, but not male mice. Our work demonstrates a female-specific mechanism for the promotion of chronic pain involving the neuroendrocrine system and mediated by sensory neuronal prolactin receptor.
bak1-5mutation uncouples tryptophan-dependent and independent postinvasive immune pathways triggered in Arabidopsis by multiple fungal pathogens
Authors: Kosaka Ayumi , Pastorczyk Marta , Piślewska-Bednarek Mariola , Nishiuchi Takumi , Suemoto Haruka , Ishikawa Atsushi , Frerigmann Henning , Kaido Masanori , Mise Kazuyuki , Bednarek Paweł , Takano Yoshitaka
Published: April 2020

Robust nonhost resistance ofArabidopsis thalianaagainst the nonadapted hemibiotrophic fungusColletotrichum tropicalerequires PEN2-dependent preinvasive and CYP71A12/CYP71A13-dependent postinvasive resistance, which both rely on tryptophan (Trp) metabolism. Here we report that CYP71A12 and CYP71A13 are critical for Arabidopsis’ postinvasive resistance toward both the necrotrophicAlternaria brassicicolaand the adapted hemibiotrophicC. higginsianumfungi. Metabolite analyses suggest that the production of indole-3-carboxylic acid derivatives (ICAs) and camalexin is induced upon pathogen invasion, while phenotypic comparison ofcyp79B2 cyp79B3andpen2 cyp71A12 cyp71A13plants indicates that the contribution of ICAs to postinvasive resistance is dose-dependent. We also found that the disruption of intact pattern recognition receptor complex caused bybak1–5mutation significantly reduced postinvasive resistance againstC. tropicaleandA. brassicicola, indicating that pattern recognition commonly contributes to this second defense-layer against pathogens with distinct infection strategies. However, thebak1–5mutation had no detectable effects on Trp-metabolite accumulation triggered by pathogen invasion. Together with this, further comparative gene expression analyses suggested that pathogen invasion in Arabidopsis activates (i)bak1–5insensitive Trp-metabolism that leads to antimicrobial secondary metabolites, and (ii) abak1–5sensitive immune pathway that activates the expression of antimicrobial proteins.
Cooperative stator assembly of bacterial flagellar motor mediated by rotation
Authors: Ito Kenta I. , Nakamura Shuichi , Toyabe Shoichi
Published: April 2020

Cooperativity has a central place in biological regulation, providing robust and highly-sensitive regulation. The bacterial flagellar motor (BFM) implements autonomous torque regulation based on the stator’s nonequilibrium structure; the stator units bind to and dissociate from the motor dynamically in response to environmental changes. However, the mechanism of this dynamic assembly is not fully understood. Here, we demonstrate the cooperativity in the stator assembly dynamics. The binding is slow at the stalled state, but the rotation in either direction boosts the stator binding. Hence, once a stator unit binds, it drives the rotor and triggers the avalanche of succeeding bindings. This cooperative mechanism based on nonequilibrium allostery accords with the recently-proposed geartype coupling between the rotor and stator.
Intraflagellar transport-A deficiency attenuates ADPKD in a renal tubular- and maturation-dependent manner
Authors: Wang Wei , Silva Luciane M. , Wang Henry H. , Kavanaugh Matthew A. , Pottorf Tana S. , Allard Bailey A. , Jacobs Damon T. , Dong Rouchen , Cornelius Joseph T. , Chaturvedi Aakriti , Pritchard Michele T. , Sharma Madhulika , Slawson Chad , Wallace Darren P. , Calvet James P. , Tran Pamela V.
Published: April 2020

Primary cilia are sensory organelles built and maintained by intraflagellar transport (IFT) multi-protein complexes. Deletion of different IFT-B genes attenuates polycystic kidney disease (PKD) severity in juvenile and adult Autosomal Dominant (AD) PKD mouse models, while deletion of an IFT-A adaptor,Tulp3, attenuates PKD severity in adult mice only. These studies indicate that dysfunction of specific cilia components has potential therapeutic value. To broaden our understanding of cilia dysfunction and its therapeutic potential, here we investigate the impact of global deletion of an IFT-A gene,Thm1, in juvenile and adult ADPKD mouse models. Both juvenile and adult models exhibited increased kidney weight:body weight (KW/BW) ratios, renal cysts, inflammation, lengthened renal cilia, and increased levels of the nutrient sensor, O-linked β-N-acetylglucosamine (O-GlcNAc).Thm1deletion in juvenile ADPKD mice reduced KW/BW ratios and cortical collecting duct cystogenesis, but increased proximal tubular and glomerular dilations and did not reduce inflammation, cilia lengths, and O-GlcNAc signaling. In contrast,Thm1deletion in adult ADPKD mice markedly attenuated renal cystogenesis, inflammation, cilia lengths, and O-GlcNAc. Thus, unlike IFT-B genes, the role ofThm1deletion in ADPKD mouse models is development-specific. Unlike an IFT-A adaptor gene, deletingThm1in juvenile ADPKD mice is partially ameliorative. Our studies suggest that different microenvironmental factors found in distinct nephron segments and between developing and mature kidneys modify ciliary homeostasis and ADPKD pathobiology. Further, elevated levels of O-GlcNAc, which regulates cellular metabolism and ciliogenesis, may be a novel feature and critical regulator of certain key ADPKD pathological processes.
A fully open-source framework for deep learning protein real-valued distances
Authors: Adhikari Badri
Published: April 2020

As deep learning algorithms drive the progress in protein structure prediction, a lot remains to be studied at this emerging crossway of deep learning and protein structure prediction. Recent findings show that inter-residue distance prediction, a more granular version of the well-known contact prediction problem, is a key to predict accurate models. We believe that deep learning methods that predict these distances are still at infancy. To advance these methods and develop other novel methods, we need a small and representative dataset packaged for fast development and testing. In this work, we introduce Protein Distance Net (PDNET), a dataset derived from the widely used DeepCov dataset and consists of 3456 representative protein chains for training and validation. It is packaged with all the scripts that were used to curate the dataset, generate the input features and distance maps, and scripts with deep learning models to train, validate and test. Deep learning models can also be trained and tested in a web browser using free platforms such as Google Colab. We discuss how this dataset can be used to predict contacts, distance intervals, and real-valued distances (in Å) by designing regression models. All scripts, training data, deep learning code for training, validation, and testing, and Python notebooks are available athttps://github.com/ba-lab/pdnet/.
Experimental multi-species microbial (co)evolution results in local maladaptation
Authors: Castledine Meaghan , Padfield Daniel , Buckling Angus
Published: April 2020

Interspecific coevolutionary interactions can result in rapid biotic adaptation, but most studies have focused only on species pairs. Here, we (co)evolved five microbial species in replicate polycultures and monocultures and quantified local adaptation. Specifically, growth rate assays were used to determine adaptations of each species’ populations to (1) the presence of the other four species in general and (2) sympatric vs allopatric communities. We found no evidence for general biotic adaptation: ancestral, polyculture- and monoculture-evolved populations did not have significantly different growth rates when measured within communities. However, 4/5 species’ growth rates were significantly lower within the community they evolved in. This “local maladaptation” suggests that species evolved increased competitive interactions to sympatric species’ populations. This increased competition did not affect community stability or productivity. Our results suggest that (co)evolution within communities can increase competitive interactions that are specific to (co)evolved community members.
Quality control of low-frequency variants in SARS-CoV-2 genomes
Authors: Rayko Mikhail , Komissarov Aleksey
Published: April 2020

During the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. We explored the variations in the submitted genomes and found a significant number of variants that can be seen only in one submission (singletons). While it is not completely clear whether these variants are erroneous or not, these variants show lower transition/transversion ratio. These singleton variants may influence the estimations of the viral mutation rate and tree topology. We suggest that genomes with multiple singletons even marked as high-covered should be considered with caution. We also provide a simple script for checking variant frequency against the database before submission.