bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting Value Through Patient-Centered Communication: A Multisite Validity Study of Third-Year Medical Students
Authors: Natt Neena , Dekhtyar Michael , Park Yoon Soo , Shinkai Kanade , Carney Patricia A. , Fancher Tonya L. , Lawson Luan , Leep Hunderfund Andrea N.
Published: May 2020

Purpose

To examine validity evidence for a standardized patient scenario assessing medical students’ ability to promote value using patient-centered communication (in response to a patient requesting an unnecessary test) and to explore the potential effect of various implementation and curricular factors on student scores.

Method

Third-year medical students (N = 516) from 5 U.S. MD-granting medical schools completed the communication scenario between 2014 and 2017 as part of a larger objective structured clinical examination (OSCE). Centralized raters assessed performance using an 11-item checklist. The authors collected multiple sources of validity evidence.

Results

The mean checklist score was 0.85 (standard deviation 0.09). Interrater reliability for checklist scores was excellent (0.87, 95% confidence interval = 0.78–0.93). Generalizability and Phi-coefficients were, respectively, 0.65 and 0.57. Scores decreased as the number of OSCE stations increased (r = −0.15, P = .001) and increased when they were used for summative purposes (r = 0.26, P < .001). Scores were not associated with curricular time devoted to high-value care (r = 0.02, P = .67) and decreased when more clerkships were completed before the assessment (r = −0.12, P = .006).

Conclusions

This multisite study provides validity evidence supporting the use of scenario scores to assess the ability of medical students to promote value in clinical encounters using patient-centered communication. Findings illuminate the potential effect of OSCE structure and purpose on student performance and suggest clerkship learning experiences may not reinforce what students are taught in the formal curriculum regarding high-value care. Devoting more time to the topic appears insufficient to counteract this erosion.
Reconstruction of Neglected Peroneal Tendon Dislocation Associated With a Large Lateral Malleolar Avulsion Fragment: A Case Study
Authors: Lynch-Wong Matthew , Walls Andrew , Wong-Chung John
Published: May 2020

Peroneal tendon dislocation not infrequently passes undiagnosed, even in the presence of a lateral malleolar avulsion fragment, which can be small or large. The surgical treatment of a symptomatic dislocation without a bony avulsion or with a small bony avulsion consists simply of incising the superior peroneal retinaculum and reattaching it to the posterolateral margin of the fibula. In case of a large bony avulsion, the superior peroneal retinaculum must be left intact and must not be incised. Instead, the periosteum overlying the acute fracture site or over the healed fracture site in a neglected case as presented herein, is incised and periosteal flaps elevated to gain surgical access and permit an imbricated reconstruction of the retinaculum.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Transumbilical Single-port Robotically Assisted Nipple-sparing Mastectomy: A Cadaveric Study
Authors: Sarfati Benjamin , Toesca Antonio , Roulot Aurélie , Invento Alessandra
Published: May 2020

The authors performed a transumbilical, single-port robotically assisted, nipple-sparing mastectomy on a cadaveric model to assess technical feasibility. Surgeon-controlled, robotic-wristed instrumentation, as well as 3-dimensional high definition (HD) vision allowed the entire dissection to be performed through a single incision placed in the umbilicus. The technique warrants further exploration and development before any application in clinical applied research.
Special International Society of Plastic Regenerative Surgeons Scientific Program in San Diego, United States
Authors: Luna Jacqueline , Pu Lee L. Q.
Published: May 2020

The International Society of Plastic Regenerative Surgeons (ISPRES) has evolved over the years since its rebirth as an affiliated organization of the American Society of Plastic Surgeons. Over the years, ISPRES has held 6 International Congresses throughout the world. Recently, the ISPRES again had a strong and positive impact at the American Society of Plastic Surgeon’s Annual Meeting held on September 19–24, 2019, in San Diego, California. A series of educational programming dedicated to fat grafting and regenerative plastic surgery took place on September 22 known as the ISPRES Dedicated Track. Overall, there were >300 attendees throughout the day who attended our ISPRES scientific program. Many of them were international attendees from many countries. In addition, more than half of the invited speakers were also international. The interests of learning from attendees and of sharing from invited speakers on fat grafting and its new role of regenerative plastic surgery again demonstrate an important value of those scientific panels organized by ISPRES. We are all looking forward to our future world congresses with excitement. Under the capable administrative support from American Society of Plastic Surgeons, ISPRES, this new dynamic society with their primary focus on fat grafting and regenerative surgery will definitely look for more worldwide educational opportunities and will lead this subspecialty of plastic surgery to the next level of excellence.
Improving the Detection of Glaucoma and Its Progression: A Topographical Approach
Authors: Hood Donald C. , Zemborain Zane Z. , Tsamis Emmanouil , De Moraes Carlos Gustavo
Published: May 2020

Glaucoma is typically defined as a progressive optic neuropathy characterized by a specific (arcuate) pattern of visual field (VF) and anatomic changes. Therefore, we should be comparing arcuate patterns of damage seen on VFs with those seen on optical coherence tomography (OCT) maps. Instead, clinicians often use summary metrics such as VF pattern standard deviation, OCT retinal nerve fiber (RNF) global thickness, etc. There are 2 major impediments to topographically comparing patterns of damage on VF and OCT maps. First, until recently, it was not easy to make these comparisons with commercial reports. While recent reports do make it easier to compare VF and OCT maps, they have shortcomings. In particular, the 24-2 VF covers a larger retinal region than the commercial OCT scans, and, further, it is not easy to understand the topographical relationship among the different maps/plots within the current OCT reports. Here we show how a model of RNF bundles can overcome these problems. The second major impediment is the lack of a quantitative, and automated, method for comparing patterns of damage seen on VF and OCT maps. However, it is now possible to objectively and automatically quantify this agreement. Together, the RNF bundle model and the automated structure-function method should improve the power of topographical methods for detecting glaucoma and its progression. This should prove useful in clinical studies and trials, as well as for training and validating artificial intelligence/deep learning approaches for these purposes.
Efficacy of Combined Suprachoroidal Stent and Cataract Surgery in Patients With Glaucoma
Authors: Law Simon K. , Salazar Diana , Yu Fei , Giaconi JoAnn A. , Chen Angela , Chopra Vikas , Francis Brian , Coleman Anne L. , Lu Kenneth , Nouri-Mahdavi Kouros , Tan James , Caprioli Joseph
Published: May 2020

Purpose:

The purpose of this study was to evaluate the efficacy of intraocular pressure (IOP) control after combined CyPass Micro-Stent implantation and cataract surgery (combined surgery).

Methods:

All cases of combined surgery performed from February 2017 to July 2018 at Stein and Doheny Eye Institutes were reviewed. The primary outcome was a qualified success with stratified IOP targets based on criteria: final IOP (A) ≤18 mm Hg and reduction of 20%, (B) ≤15 mm Hg and reduction of 25%, (C) ≤12 mm Hg and reduction of 30%. Secondary outcome measures included postoperative IOP and number of medications, complications, additional glaucoma surgery, and postoperative refractive error. Predictive factors for failure were investigated. IOP spike was defined as a postoperative IOP ≥30 or >10 mm Hg increase from preoperative IOP.

Results:

One hundred forty-one eyes (107 patients) were included. Mean (±SD) preoperative IOP was 15.4±3.4 mm Hg on an average of 2.2±1.1 medications. A statistically significant reduction in IOP and number of medications was seen at 12 months (13.8±4.2 mm Hg, 1.3±1.3 medications, P<0.001). Fifteen eyes (10.6%) had a postoperative IOP spike. Thirteen eyes (9.2%) experienced 17 complications (12.1%). Additional glaucoma surgery was performed in 3 eyes (2 patients). Cumulative success rates at 1 year based on criteria A, B, and C were 42%, 33%, and 28%, respectively. Lower preoperative IOP, greater preoperative medication number, the occurrence of postoperative IOP spike, and non-Caucasian ethnicity were associated with failure.

Conclusion:

Combined CyPass Micro-Stent implantation and cataract surgery may reduce glaucoma medication burden with a success rate of 28% to 42% at 1 year.
Comparison of self- and nurse-measured office blood pressure in patients with chronic kidney disease
Authors: Tougaard Birgitte Godskesen , Laursen Kathrine Skaaning , Jensen Jens Dam , Buus Niels Henrik
Published: May 2020

Objective

As blood pressure (BP) control is very important in chronic kidney disease (CKD), we investigated how office BP is influenced by the measurement circumstances and compared nonautomated self- and nurse-measured BP values.

Materials and methods

Two hundred stage 1–5 CKD patients with scheduled visits to an outpatient clinic were randomized to either self-measured office BP (SMOBP) followed by nurse-measured office BP (NMOBP) or NMOBP followed by SMOBP. The participants had been educated to perform the self-measurement in at least one previous visit. The SMOBP and NMOBP measurement series both consisted of three recordings, and the means of the last two recordings during SMOBP and NMOBP were compared for the 174 (mean age 52.5 years) with complete BP data.

Results

SMOBP and NMOBP showed similar systolic (135.3 ± 16.6 vs 136.4 ± 17.4 mmHg, Δ = 1.1 mmHg, P = 0.13) and diastolic (81.5 ± 10.2 vs 82.2 ± 10.4 mmHg, Δ = 0.6 mmHg, P = 0.09) values. The change in BP from the first to the third recording was not different for SMOBP and NMOBP. In 17 patients, systolic SMOBP was ≥10 mmHg higher than NMOBP and in 28 patients systolic NMOBP exceeded SMOBP by ≥10 mmHg. The difference between systolic SMOBP and NMOBP was independent of CKD stage and the number of medications, but significantly more pronounced in patients above 60 years.

Conclusion

In a population of CKD patients, there is no clinically relevant difference in SMOBP and NMOBP when recorded at the same visit. However, in 25% of the patients, systolic BP differs ≥10 mmHg between the two measurement modalities.
North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper
Authors: Merritt Russell J. , Fleet Sarah E. , Fifi Amanda , Jump Candi , Schwartz Sally , Sentongo Timothy , Duro Debora , Rudolph Jeffrey , Turner Justine ,   NASPGHAN Committee on Nutrition
Published: May 2020

Parents and caretakers are increasingly feeding infants and young children plant‐based “milk” (PBM) alternatives to cow milk (CM). The US Food and Drug Administration currently defines “milk” and related milk products by the product source and the inherent nutrients provided by bovine milk. Substitution of a milk that does not provide a similar nutritional profile to CM can be deleterious to a child's nutritional status, growth, and development. Milk's contribution to the protein intake of young children is especially important. For almond or rice milk, an 8 oz serving provides only about 2% or 8%, respectively, of the protein equivalent found in a serving of CM. Adverse effects from the misuse of certain plant‐based beverages have been well‐documented and include failure to gain weight, decreased stature, kwashiorkor, electrolyte disorders, kidney stones, and severe nutrient deficiencies including iron deficiency anemia, rickets, and scurvy. Such adverse nutritional outcomes are largely preventable. It is the position of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Nutrition Committee, on behalf of the society, that only appropriate commercial infant formulas be used as alternatives to human milk in the first year of life. In young children beyond the first year of life requiring a dairy‐free diet, commercial formula may be a preferable alternative to cow's milk, when such formula constitutes a substantial source of otherwise absent or reduced nutrients (eg, protein, calcium, vitamin D) in the child's restricted diet. Consumer education is required to clarify that PBMs do not represent an equivalent source of such nutrients. In this position paper, we provide specific recommendations for clinical care, labelling, and needed research relative to PBMs.
Clinical presentation of paroxysmal supraventricular tachycardia: evaluation of usual and unusual symptoms
Authors: Yetkin Ertan , Ozturk Selcuk , Cuglan Bilal , Turhan Hasan
Published: May 2020

Objective

Clinical presentation of paroxysmal supraventricular tachycardia may vary from asymptomatic occurrence or mild perception of palpitation to severe chest pain or syncope. This variation is the most challenging issue in the diagnostic evaluation of rhythm disturbances and paroxysmal supraventricular tachycardia as well. This study sought to evaluate the symptoms during the tachycardia attack or index event in patients who underwent electrophysiological study and ablation procedure.

Methods

This retrospective study included 100 consecutive patients who underwent electrophysiological study and ablation procedures due to supraventricular tachycardia. Structural heart disease, moderate/severe valvular pathology, systemic pathologies, such as connective tissue disease and chronic obstructive lung disease, history of pacemaker implantation was defined as exclusion criteria. In addition, medically managed patients and patients with unsuccessful ablation were not included in the study.

Results

Palpitation was the most frequently observed symptom in 84% of patients, followed by chest pain in 47%, dyspnea in 38%, syncope 26%, lightheadedness in 19%, and sweating in 18% of the patients. The most common symptoms after tachycardia event were fatigue and lightheadedness with frequencies of 56% and 55%, respectively. Forty-five percent of the patients reported more than one, unusually frequent urination within the following 1–3 hours after the index event.

Conclusions

Paroxysmal supraventricular tachycardia might manifest itself as gastrointestinal, neurological, psychosomatic symptoms, and unusual complaints in association with or without main symptoms, including palpitation, chest pain, syncope, and dyspnea. Symptoms after tachycardia or index event should be questioned systematically.
Predictors of 1-year rehospitalization in inpatients with bipolar I disorder treated with atypical antipsychotics
Authors: Um Yoo Hyun , Kim Tae-Won , Seo Ho-Jun , Hong Seung-Chul , Kim Sung-Min , Oh Ji-Hye , Jeong Jong-Hyun
Published: May 2020

Bipolar disorder (BPD) is debilitating disorder, and patients can experience multiple relapses and subsequent hospitalizations. Since pharmacotherapy is the mainstay of treatment for patients with BPD, investigations on the effects of atypical antipsychotics (AAP) on reducing rehospitalization risk are crucial. The objective of study is to explore predictors of 1-year rehospitalization in patients with bipolar I disorder treated with AAP. A retrospective chart review on inpatients with bipolar I disorder was conducted. All participants were followed up for 1 year, and they were subdivided into three AAP treatment groups (olanzapine, risperidone, and quetiapine group). Kaplan–Meier survival analysis was implemented to detect time to rehospitalization due to any mood episodes within 1 year after discharge. Cox proportional regression model was adopted to find predictors of 1-year hospitalization in patients who experienced rehospitalization. One hundred thirty-eight participants were included in the study, and a 1-year rehospitalization rate was 18.1%. Time to rehospitalization did not differ between three AAP treatment groups. Predictors of rehospitalization due to any episode within 1 year were family history of depression and number of previous admission. Our findings can be conducive to understanding prognosis, and predicting rehospitalization risk in patients with BPD on AAP.
Prolonged viral shedding and new mutations of COVID-19 could complicate the control of the pandemic
Authors: Chen Chieh-Fan , Tsai Tung-Yuan , Yu Chen-Hui , Cheng Hsiang-Lan , Yeh Ting-Yu
Published: May 2020

The studies of coronavirus disease 2019 (COVID-19) have mainly focused on epidemiological and clinical features of patients, but transmission dynamics of SARS-CoV-2 virus after patients have recovered is still poorly understood. Here we report a case with prolonged viral shedding of COVID-19 in Kaohsiung, Taiwan. This patient started to show myalgia and malaise in Wuhan, and the onset of the fever was on days 7–14 of the illness. All clinical and radiological results returned to normal after day 26, however, viral shedding was still evident 14 days later. Sequence analysis of the genome of the Taiwanese SARS-CoV-2 isolate from this patient reveals new mutations in viral replicase and ORF3a, indicating that COVID-19 evolves very quickly. Prolonged viral shedding and new mutations in the viral genome could potentially complicate the control of the COVID-19 pandemic.
Corynebacterium urogenitale sp. nov. isolated from the genital tract of a cow
Authors: Ballas Panagiotis , Rückert Christian , Wagener Karen , Drillich Marc , Kämpfer Peter , Busse Hans-Jürgen , Ehling-Schulz Monika
Published: May 2020

A Gram-stain-positive bacterial isolate, designated LMM-1652T, was isolated from an intrauterine cytobrush sample originating from a postpartum Holstein Friesian dairy cow. The strain had a rod to coccoid-shape, was catalase-positive and oxidase-negative. 16S rRNA gene sequence similarity analyses revealed that its closest relatives were

Corynebacterium falsenii

(97.05 % similarity),

Corynebacterium jeikeium

(96.83 %) and

Corynebacterium urealyticum

(96.82 %). Subsequent whole genome analysis showed that the genome-to-genome distance of strain LMM-1652T to its closest relatives was in the range of 23.2–24.8 %, while the average
nucleotide identity values ranged from 73.7 to 74.3%, thus confirming that this isolate represents a novel species. Strain LMM-1652T was characterized by a quinone system mainly consisting of MK-9(H2) and MK-10(H2). The polar lipids profile of the strain consisted mainly of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol-mannoside, as well as one unidentified lipid lacking any functional group. Smaller amounts of four unidentified phospholipids, four unidentified glycolipids, β-gentiobiosyl diacylglycerol and four unidentified lipids lacking a functional group were also found. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid of the peptidoglycan. The fatty acid profile was mainly composed of C18 : 1 ω9c, C18 : 0 and C16 : 0. We propose a novel species of the genus

Corynebacterium

with the name Corynebacterium urogenitale LMM-1652T (=LMG 31163T=DSM 108747T).
Evaluation of the usefulness of selected methods for the detection of carbapenemases in Klebsiella strains
Authors: Sękowska Alicja , Bogiel Tomasz , Kaczmarek Agnieszka
Published: May 2020

Introduction.

Klebsiella

rods, belonging to the family

Enterobacteriaceae

, are generally opportunistic pathogens commonly associated with nosocomial infections, especially in intensive care units. Interestingly, strains of this genus also show multi-drug resistance. In recent years, multiple studies have indicated that the prevalence of carbapenem resistance has increased rapidly among

Klebsiella

representatives.

Aim. The aim of this study was to assess the usefulness of selected phenotypic and genotypic methods for the detection of the most important carbapenemases in

Klebsiella

strains.

Methodology. The study involved 51

Klebsiella

strains. The ability to produce carbapenemases was determined by phenotypic methods (double disc synergy test, test with four discs and three inhibitors, CarbaNP test, culture on chromogenic medium, panels of automatic method – Phoenix, CIM test and modified Hodge test). The potential for carbapenemase synthesis was also evaluated using real-time PCR, detecting bla
VIM/IMP, bla
KPC, bla
NDM and bla
OXA-48 genes.

Results. Using the phenotypic methods, positive results were obtained for all of the analysed strains. Using PCR, carbapenemase synthesis potential was confirmed on the molecular level; the bla
VIM gene was detected in 23 strains, the bla
NDM gene in 26 strains and the bla
OXA-48 gene in two strains.

Conclusion. There was complete agreement between the carbapenemases detected by the genetic method and the results obtained with phenotypic methods.
In vitro bactericidal activity of a carbohydrate polymer with zinc oxide for the treatment of chronic wounds
Authors: Bello-López Juan Manuel , López-Ornelas Adolfo , Vilchis-Rangel Rodolfo Erik , Ribas-Aparicio Rosa María , Del-Moral Pamela , Donis-Rocandio Jenny Elizabeth , Cueto Jorge , Aparicio-Ozores Gerardo , Moreno José
Published: May 2020

Introduction. Biological adhesives and effective topical therapeutic agents that improve wound healing are urgently required for the treatment of chronic ulcers. A biodegradable adhesive based on a carbohydrate polymer with zinc oxide (CPZO) was shown to possess anti-inflammatory activity and enhance wound healing, but its bactericidal activity was unknown.

Aim. To investigate the bactericidal activity of CPZO against bacteria commonly present as infectious agents in chronic wounds.

Methodology. We examined the bactericidal activity of CPZO against three biofilm-producing bacteria (

Staphylococcus aureus

,

Escherichia coli

and

Pseudomonas aeruginosa

) through three strategies: bacterial suspension, biofilm disruption and in vitro wound biofilm model.

Results. In suspension cultures, CPZO had direct, potent bactericidal action against

S. aureus

within 24 h, whereas

E. coli

took 7 days to be eliminated. By contrast,

P. aeruginosa

survived up to 14 days with CPZO. CPZO had biofilm disruption activity against clinical isolates of

S. aureus

in the anti-biofilm test. Finally, in the in vitro wound biofilm model, CPZO dramatically reduced the bacterial viability of

S. aureus

and

P. aeruginosa

.

Conclusions. Together with its previously shown anti-inflammatory properties, the bactericidal activity of CPZO gives it the potential to be a first-line therapeutic option for chronic various ulcers and, possibly, other chronic ulcers, preventing or controlling microbial infections, and leading to the healing of such complicated chronic ulcers.
Magnesium Sulfate Attenuates Lethality and Oxidative Damage Induced by Different Models of Hypoxia in Mice
Authors: Mohammadi Hamidreza , Shamshirian Amir , Eslami Shafagh , Shamshirian Danial , Ebrahimzadeh Mohammad Ali
Published: May 2020

Mg2+is an important cation in our body. It is an essential co-factor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO4against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO4were evaluated by three experimental models of induced-hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO4were evaluated in mice brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia where MgSO4at dose 600 mg/kg showed the same activity as phenytoin which used as a positive control (P<0.001). In the haemic model, MgSO4at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO4(600 mg/kg) doubles the survival time. MgSO4significantly decreased Lipid peroxidation, protein carbonyl, and improved mitochondrial function and glutathione content in brain mitochondria compared to control groups. The results obtained in this study showed that MgSO4administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage.
Nanaerobic growth enables direct visualization of dynamic cellular processes in human gut symbionts
Authors: García-Bayona Leonor , Coyne Michael J. , Hantman Noam , Montero-Llopis Paula , Von Salena , Ito Takeshi , Malamy Michael H. , Basler Marek , Barquera Blanca , Comstock Laurie E.
Published: May 2020

Mechanistic studies of anaerobic gut bacteria have been hindered by the lack of a fluorescent protein system to track and visualize proteins and dynamic cellular processes in actively growing bacteria. Although underappreciated, many gut “anaerobes” are able to respire using oxygen as the terminal electron acceptor. The oxygen continually released from gut epithelial cells creates an oxygen gradient from the mucus layer to the anaerobic lumen (1), with oxygen available to bacteria growing at the mucus layer. Using a combination of analyses, we show thatBacteroidesspecies are metabolically and energetically robust and do not mount stress responses in the presence of 0.10 - 0.14% oxygen, defined as nanaerobic conditions (2). Taking advantage of this metabolic capability, we show that nanaerobic growth provides sufficient oxygen for the maturation of oxygen-requiring fluorescent proteins inBacteroidesspecies. Type strains of four differentBacteroidesspecies show bright GFP fluorescence when grown nanaerobically versus anaerobically. We compared four different red fluorescent proteins and found that mKate2 yields high fluorescence intensity in our assay. We show that GFP-tagged proteins can be localized in nanaerobically growing bacteria. In addition, we used time-lapse fluorescence microscopy to image dynamic Type VI secretion system processes in metabolically activeB. fragilis. The ability to visualize fluorescently-labeledBacteroidesand fluorescently-linked proteins in actively growing nanaerobic gut symbionts ushers in a new age of imaging analyses in these bacteria.

Significance

Despite many recent technological advances to study the human gut microbiota, we still lack a facile system to image dynamic cellular processes in most abundant gut species due to the requirement of oxygen for chromophore maturation of commonly used fluorescent proteins. Here, we took advantage of the ability of anaerobes of the gut microbiota to respire aerobically and grow robustly at 0.10– 0.14% oxygen. This physiologic concentration of oxygen is sufficient for fluorescent proteins to mature, allowing for visualization of biological processes never before imaged in these bacteria. This advance will allow for numerous types of analyses in actively-growing “nanaerobic” gut bacteria including subcellular protein localizations, single-cell analyses, biofilm imaging, and protein interactions with other microbes and the host.
Digitization of Electrocardiogram Using Bilateral Filtering
Authors: Sankar S Hari , Patni Anchit , Mulleti Satish , Seelamantula Chandra Sekhar
Published: May 2020

Electrocardiogram (ECG) is one of the most basic tools available for the detection of cardiovascular disease (CVD) which has evolved as one of the major causes of death in recent times, spanning countries. Conventionally, ECGs are printed on graph sheets which keep fading away with time. Hence, the preservation of ECG graph sheets is difficult. Digitization of printed ECG graph sheets is a solution to this problem. Digitization also helps in faster analysis and interpretation of ECG signals. Although the previous works have succeeded in smoothing ECG after extracting the signal from graph sheet, the cost amounts to loss of peak amplitude characteristics leading to wrong diagnosis. In this work, we propose a digitization technique to extract ECG signals from graph sheets. The proposed bilateral filter based method achieves a high degree of smoothness with all the peak characteristics intact when compared to other implementations using Butterworth filters. With this technique, it is now possible to create extensive databases similar to MIT–BIH from printed ECG graph sheets. A high level of automation is achieved, and results verified with over 60 ECGs and compared.
Regional activity in the rat anterior cingulate cortex and insula during persistence and quitting in a physical-effort task
Authors: Porter Blake S. , Li Kunling , Hillman Kristin L.
Published: May 2020

As animals carry out behaviors, particularly costly ones, they must constantly assess whether or not to persist in the behavior or quit. The anterior cingulate cortex (ACC) has been shown to assess the value of behaviors and to be especially sensitive to physical effort costs. Complimentary to these functions, the insula is thought to represent the internal state of the animal including factors such as hunger, thirst, and fatigue. Utilizing a novel weight lifting task for rats, we characterized the local field potential (LFP) activity of the ACC and anterior insula (AI) during effort expenditure. In the task male rats are challenged to work for sucrose reward, which costs progressively more effort over time to obtain. Rats are able to quit the task at any point. We found modest shifts in LFP theta (7-9 Hz) activity as the task got progressively more difficult in terms of absolute effort expenditure. However, when the LFP data were analyzed based on the rat’s relative progress towards quitting the task, or performance state, substantial shifts in LFP power in the theta and gamma (55-100 Hz) frequency bands were observed in ACC and AI. Both ACC and AI theta power decreased as the rats got closer to quitting, while ACC and AI gamma power increased. Furthermore, coherency between ACC and AI in the delta (2-4 Hz) range shifted alongside the rat’s performance state. Overall we show that ACC and AI LFP activity changes correlate to the rats’ relative performance state in an effort-based task.

Significance Statement

Animals need to assess whether or not a behavior is worth pursuing based on their internal states (e.g., hunger, fatigue) and the costs and benefits of the behavior. However, internal states often change as behaviors are carried out, such as becoming fatigued, necessitating constant reassessment as to whether to continue the behavior or quit. We characterized brain activity in the anterior cingulate cortex and insula, brain regions involved in cost-benefit decision making and internal state representations, respectively, as rats carried out a challenging physical-effort task. Both brain regions showed significant shifts in activity as the rats approached their quitting point. Our study provides one of the first characterizations of neural activity as an animal decides to quit an effortful task.
For-profit nursing homes and the risk of COVID-19 outbreaks and resident deaths in Ontario, Canada
Authors: Stall Nathan M. , Jones Aaron , Brown Kevin A. , Rochon Paula A. , Costa Andrew P.
Published: May 2020

Background

Nursing homes have become the epicentre of the coronavirus disease 2019 (COVID-19) pandemic in Canada. Previous research demonstrates that for-profit nursing homes deliver inferior care across a variety of outcome and process measures, raising the question of whether for-profit homes have had worse COVID-19 outcomes than non-profit homes.

Methods

We conducted a retrospective cohort study of all nursing homes in Ontario, Canada from March 29-May 20, 2020 using a COVID-19 outbreak database maintained by the Ontario Ministry of Long-Term Care. We used hierarchical logistic and count-based methods to model the associations between nursing home profit status (for-profit, non-profit or municipal) and nursing home COVID-19 outbreaks, COVID-19 outbreak sizes, and COVID-19 resident deaths.

Results

The analysis included all 623 Ontario nursing homes, of which 360 (57.7%) were for-profit, 162 (26.0%) were non-profit, and 101 (16.2%) were municipal homes. There were 190 (30.5%) COVID-19 nursing home outbreaks involving 5218 residents (mean of 27.5 ± 41.3 residents per home), resulting in 1452 deaths (mean of 7.6 ± 12.7 residents per home) with an overall case fatality rate of 27.8%. The odds of a COVID-19 outbreak was associated with the incidence of COVID-19 in the health region surrounding a nursing home (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI] 1.23-3.09) and number of beds (aOR, 1.40; 95% CI 1.20-1.63), but not profit status. For-profit status was associated with both the size of a nursing home outbreak (adjusted risk ratio [aRR], 1.96; 95% CI 1.26-3.05) and the number of resident deaths (aRR, 1.78; 95% CI 1.03-3.07), compared to non-profit homes. These associations were mediated by a higher prevalence of older nursing home design standards in for-profit homes.

Interpretation: For-profit status is associated with the size of a COVID-19 nursing home outbreak and the number of resident deaths, but not the likelihood of outbreaks. Differences between for profit and non-profit homes are largely explained by older design standards, which should be a focus of infection control efforts and future policy.
Constraining the contribution of aerobic nitrite oxidation to oxygen consumption in oceanic oxygen minimum zones
Authors: Beman J.M. , Vargas S.M. , Wilson J.M. , Perez-Coronel E. , Karolewski J.S. , Vazquez S. , Yu A. , Cairo A.E. , White M.E. , Koester I. , Aluwihare L. I. , Wankel S.D.
Published: May 2020

Oceanic oxygen minimum zones (OMZs) are globally significant sites of biogeochemical cycling where microorganisms deplete dissolved oxygen (DO) to concentrations <20 µM. Amid intense competition for DO in these metabolically challenging environments, aerobic nitrite oxidation may consume significant amounts of DO and help maintain low DO concentrations, but this remains unquantified. Using parallel measurements of oxygen consumption rates and15N-nitrite oxidation rates applied to both water column profiles and oxygen manipulation experiments, we show that the contribution of nitrite oxidation to overall DO consumption systematically increases as DO declines below 2 µM. Nitrite oxidation could account for all DO consumption only under DO concentrations <393 nM found in and below the secondary chlorophyll maximum. These patterns were consistent across sampling stations and experiments, reflecting coupling between nitrate reduction and nitrite-oxidizingNitrospinawith high oxygen affinity (based on isotopic and omic data). Collectively our results provide new insight into the contribution of nitrite oxidation to the maintenance and biogeochemical dynamics of OMZs.
Non-Canonical Ago Loading of EV-Derived Exogenous miRNA Generates Foreign miRNPs on Endosomes to Arbitrate Gene Expression in Recipient Cells
Authors: Ghoshal Bartika , Bertrand Edouard , Bhattacharyya Suvendra N.
Published: May 2020

MicroRNAs, the tiny regulators of gene expression, can be transferred between neighbouring cells via Extracellular Vesicles (EV) to control the expression of genes in both donor and recipient cells. How the Extracellular Vesicles-derived miRNAs are getting internalized and become functional in target cells is an unresolved question. We found that EV-associated miRNAs are primarily single stranded and, to become functional, get loaded with the Ago proteins present in the recipient cells without requiring host Dicer1. Following endocytosis of miRNA-containing extracellular vesicles, loading of host Ago occurs on the endosomal membrane where pH-dependent membrane fusion triggers the release of internalized miRNAs to form exogenous miRNP pool. In addition, loading of exogenous miRNA to host Ago also depends on the mitochondrial activity of recipient cells. Internalization of hepatocyte derived miR-122 containing EVs in macrophage activates the recipient cell by targeting cytokine expression.Leishmania donovani, a protozoan parasite known to affect endocytosis and to cause mitochondrial depolarization in infected macrophages, restricts the EV-internalization process and thereby preventing inflammatory cytokine expression and ensuring internalized pathogen survival in macrophage.
Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir
Authors: Lo Ho Sing , Hui Kenrie Pui Yan , Lai Hei-Ming , Khan Khadija Shahed , Kaur Simranjeet , Huang Junzhe , Li Zhongqi , Chan Anthony K. N. , Cheung Hayley Hei-Yin , Ng Ka-Chun , Wang Ho John Chi , Chen Yu Wai , Ma Bowen , Cheung Peter Man-Hin , Shin Donghyuk , Wang Kaidao , Lee Meng-Hsuan , Selisko Barbara , Eydoux Cecilia , Guillemot Jean-Claude , Canard Bruno , Wu Kuen-Phon , Liang Po-Huang , Dikic Ivan , Zuo Zhong , Chan Francis K. L. , Hui David S. C. , Mok Vincent C. T. , Wong Kam-Bo , Ko Ho , Aik Wei Shen , Chan Michael Chi Wai , Ng Wai-Lung
Published: May 2020

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivirin vitro. Mechanistically, we showed that simeprevir inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp). Our results thus reveal the viral protein targets of simeprevir, and provide preclinical rationale for the combination of simeprevir and remdesivir for the pharmacological management of COVID-19 patients.

One Sentence Summary

Discovery of simeprevir as a potent suppressor of SARS-CoV-2 viral replication that synergizes with remdesivir.
A global data-driven census of Salmonella small proteins and their potential functions in bacterial virulence
Authors: Venturini Elisa , Svensson Sarah L. , Maaß Sandra , Gelhausen Rick , Eggenhofer Florian , Li Lei , Cain Amy K. , Parkhil Julian , Becher Dörte , Backofen Rolf , Barquist Lars , Sharma Cynthia M. , Westermann Alexander J. , Vogel Jörg
Published: May 2020

Small proteins are an emerging class of gene products with diverse roles in bacterial physiology. However, a full understanding of their importance has been hampered by insufficient genome annotations and a lack of comprehensive characterization in microbes other than Escherichia coli. We have taken an integrative approach to accelerate the discovery of small proteins and their putative virulence-associated functions in Salmonella Typhimurium. We merged the annotated small proteome of Salmonella with new small proteins predicted with in silico and experimental approaches. We then exploited existing and newly generated global datasets that provide information on small open reading frame expression during infection of epithelial cells (dual RNA-seq), contribution to bacterial fitness inside macrophages (TraDIS), and potential engagement in molecular interactions (Grad-seq). This integrative approach suggested a new role for the small protein MgrB beyond its known function in regulating PhoQ. We demonstrate a virulence and motility defect of a Salmonella ΔmgrB mutant and reveal an effect of MgrB in regulating the Salmonella transcriptome and proteome under infection-relevant conditions. Our study highlights the power of interpreting available “omics” datasets with a focus on small proteins, and may serve as a blueprint for a data integration-based survey of small proteins in diverse bacteria.
Cataract-associated New Mutants S175G/H181Q of βB2-Crystallin and P24S/S31G of γD-Crystallin are Involved in Protein aggregation by Structural Changes
Authors: Song In-Kang , Na Seungjin , Paek Eunok , Lee Kong-Joo
Published: May 2020

β/γ-Crystallins, the main structural protein in human lenses, have highly stable structure for keeping the lens transparent. Their mutations have been linked to congenital cataracts. In this study, we identified 10 new mutations of β/γ-crystallins in lens proteomic dataset of cataract patients using bioinformatic tools. Of these, two double mutants, S175G/H181Q of βΒ2-crystallin and P24S/S31G of γD-crystallin, were found mutations occurred in the largest loop linking the distant β-sheets in the Greek key motif. We selected these double mutants for identifying the properties of these mutations, employing biochemical assay, the identification of protein modifications with nanoUPLC-ESI-TOF tandem MS and examining their structural dynamics with hydrogen/deuterium exchange-mass spectrometry (HDX-MS). We found that both double mutations decrease protein stability and induce the aggregation of β/γ-crystallin, possibly causing cataracts. This finding suggests that both the double mutants can serve as biomarkers of congenital cataracts.
Study of cell to cell transmission of SARS CoV 2 virus particle using gene network from microarray data
Authors: Basu Anamika , Sarkar Anasua , Maulik Ujjwal
Published: May 2020

Microarray data from SARS CoV2 patients helps to construct a gene network relating to this disease. Analysis of these genes, present in network, highlights their biological functions and related cellular pathways. With the assistance of these information, a drug(s) can be identified to treat COVID-19. A detailed analysis of the human host response to SARS CoV 2 with expression profiling by high throughput sequencing has executed with primary human lung epithelium cell lines. Clustered genes annotation and gene network construction are performed with the help of String database. Among four cluster of genes from microarray data, cluster 1 is identified as basal cells with p= 1.37e−05 with 44 genes. Functional enrichment analysis of genes present in gene network has completed using String database, ToppFun online tool and NetworkAnalyst tool. For SARS CoV2 virus particles, keratin proteins, which are part of cytoskeleton structure of host cell, play a major role in cell to cell virus particle transmission. Among three types of cell- cell communication, only anchoring junction between basal cell membrane and basal lamina, is involved in this virus transmission. In this junction point, hemidesmosome structure play a vital role in virus spread from one cell to basal lamina in respiratory tract. In this protein complex structure, keratin, integrin and laminin proteins of host cell is used to promote the spread of virus infection into extracellular matrix. So, small molecular blockers of different anchoring junction proteins i.e. ITGA3, ITGA2 can provide efficient protection against this deadly virus disease. Understanding the human host response against this virus is very important to develop novel therapeutics for the treatment of SARS-CoV 2.
Role of Diversity-Generating Retroelements for Regulatory Pathway Tuning in Cyanobacteria
Authors: Vallota-Eastman Alec , Arrington Eleanor C. , Meeken Siobhan , Roux Simon , Dasari Krishna , Rosen Sydney , Miller Jeff F. , Valentine David L. , Paul Blair G.
Published: May 2020

Background

Cyanobacteria maintain extensive repertoires of regulatory genes that are vital for adaptation to environmental stress. Some cyanobacterial genomes have been noted to encode diversity-generating retroelements (DGRs), which promote protein hypervariation through localized retrohoming and codon rewriting in target genes. Past research has shown DGRs to mainly diversify proteins involved in cell-cell attachment or viral-host attachment within viral, bacterial, and archaeal lineages. However, these elements may be critical in driving variation for proteins involved in other core cellular processes.

Results

Members of 31 cyanobacterial genera encode at least one DGR, and together, their retroelements form a monophyletic clade of closely-related reverse transcriptases. This class of retroelements diversifies target proteins with unique domain architectures: modular ligand-binding domains often paired with a second domain that is linked to signal response or regulation. Comparative analysis indicates recent intragenomic duplication of DGR targets as paralogs, but also apparent intergenomic exchange of DGR components. The prevalence of DGRs and the paralogs of their targets is disproportionately high among colonial and filamentous strains of cyanobacteria.

Conclusion

We find that colonial and filamentous cyanobacteria have recruited DGRs to optimize a ligand-binding module for apparent function in signal response or regulation. These represent a unique class of hypervariable proteins, which might offer cyanobacteria a form of plasticity to adapt to environmental stress. This analysis supports the hypothesis that DGR-driven mutation modulates signaling and regulatory networks in cyanobacteria, suggestive of a new framework for the utility of localized genetic hypervariation.
Rapid self-selecting and clone-free integration of transgenes into engineered CRISPR safe harbor locations inCaenorhabditis elegans
Authors: Stevenson Zachary C. , Moerdyk-Schauwecker Megan J. , Jamison Brennen , Phillips Patrick C.
Published: May 2020

Precision genome editing for model organisms has revolutionized functional analysis and validation of a wide variety of molecular systems. To date, the capacity to insert transgenes into the model nematodeCaenorhabditis eleganshas focused on utilizing either transposable elements or CRISPR-based safe harbor strategies. These methods require laborious screening processes that often result in false positives from heritable extrachromosomal arrays or rely on co-CRISPR markers to identify likely edited individuals. As a result, verification of transgene insertion requires anti-array selection screening methods or extensive PCR genotyping respectively. These approaches also rely on cloning plasmids for the addition of transgenes. Here, we present a novel safe harbor CRISPR-based integration strategy that utilizes engineered insertion locations containing a synthetic guide RNA target and a split-selection system to eliminate false positives from array formation, thereby providing integration-specific selection. This approach allows the experimenter to confirm an integration event has taken place without molecular validation or anti-array screening methods, and is capable of producing integrated transgenic lines in as little as five days post-injection. To further increase the speed of generating transgenic lines, we also utilized theC. elegansnative homology-based formation of extra-chromosomal arrays to assemble transgenesin-situ, removing the cloning step. We show that complete transgenes can be made and inserted into our split-selection safe harbor locations starting from PCR products, providing a clone-free and molecular-validation-free strategy for single-copy transgene integration. Overall, this combination of approaches provides an economical and rapid system for generating highly reproducible complex transgenics inC. elegans.