bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographic, Reproductive, and Medical Risk Factors for Intrauterine Device Expulsion
Authors: Anthony Mary S. , Zhou Xiaolei , Schoendorf Juliane , Reed Susan D. , Getahun Darios , Armstrong Mary Anne , Gatz Jennifer , Peipert Jeffrey F. , Raine-Bennett Tina , Fassett Michael J. , Saltus Catherine W. , Ritchey Mary E. , Ichikawa Laura , Shi Jiaxiao M. , Alabaster Amy , Wahdan Yesmean , Wang Jinyi , Xie Fagen , Merchant Maqdooda , Hunter Shannon , Chiu Vicki Y. , Postlethwaite Debbie , Rothman Kenneth J. , Im Theresa M. , Chillemi Giulia , Takhar Harpreet S. , Asiimwe Alex , Pisa Federica
Published: November 2022

OBJECTIVE:

To explore to what extent intrauterine device (IUD) expulsion is associated with demographic and clinical risk factors.

METHODS:

The APEX-IUD (Association of Perforation and Expulsion of IntraUterine Devices) study was a U.S. cohort study using electronic health records from three integrated health care systems (Kaiser Permanente Northern California, Southern California, and Washington) and a health care information exchange (Regenstrief Institute). These analyses included individuals aged 50 years or younger with IUD insertions from 2001 to 2018. Intrauterine device expulsion cumulative incidence and incidence rates were estimated. Using Cox regression models, hazard ratios with 95% CIs were estimated before and after adjustment for risk factors of interest (age, race and ethnicity, parity, body mass index [BMI], heavy menstrual bleeding, and dysmenorrhea) and potential confounders.

RESULTS:

In total, 228,834 individuals with IUD insertion and no delivery in the previous 52 weeks were identified (184,733 [80.7%] with levonorgestrel-releasing intrauterine system). Diagnosis of heavy menstrual bleeding—particularly a diagnosis in both recent and past periods—was the strongest risk factor for IUD expulsion. Categories with the highest risk of IUD expulsion within each risk factor included individuals diagnosed with overweight, obesity, and morbid obesity; those in younger age groups, especially among those aged 24 years or younger; and in those with parity of four or more. Non-Hispanic White individuals had the lowest incidence and risk, and after adjustment, Asian or Pacific Islander individuals had the highest risk. Dysmenorrhea was not independently associated with expulsion risk when adjusting for heavy menstrual bleeding.

CONCLUSION:

Most risk factors for expulsion identified in this study appear consistent with known physiologic factors that affect uterine anatomy and physiology (age, BMI, heavy menstrual bleeding, parity). The increased risk of IUD expulsion among individuals of color warrants further investigation. Intrauterine devices are an effective long-term contraceptive; expulsion is uncommon, but patients should be counseled accordingly.

FUNDING SOURCE:

Bayer AG.

CLINICAL TRIALS REGISTRATION:

EU PAS register, EUPAS33461.
Tip of the J-pouch Leaks: Diagnosis, Management, and Long-term Pouch Survival
Authors: Holubar Stefan D. , Rajamanickam Raja Kumaran , Gorgun Emre , Lightner Amy L. , Valente Michael A. , Church James , Hull Tracy , Steele Scott R.
Published: November 2022

BACKGROUND:

The standard of care for surgical treatment of ulcerative colitis is restorative proctocolectomy with ileal J-pouch. Leaks from tip of the J-pouch are a known complication but there is a paucity of literature regarding this type of leak.

OBJECTIVE:

To describe the diagnosis, management and long-term clinical outcomes of tip of the J-pouch leaks at our institution.

DESIGN:

Retrospective study of prospectively maintained Pouch Registry.

SETTING:

Quaternary inflammatory bowel disease referral center.

PATIENTS:

Patients with an ileal J-pouches diagnosed with tip of the J leaks.

MAIN OUTCOME MEASURES:

Pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival.

RESULTS:

We identified 74 patients with leaks from the tip of the J-pouch. Pain (68.9%) and pelvic abscess (40.9%) were the most common presentations, while 10.8% of patients presented with an acute abdomen. The leak was diagnosed by imaging and/or endoscopy in 74.3%, but only discovered during surgical exploration in 25.6%. Some 63.5% were diagnosed only after loop ileostomy closure, while 32.4% were before ileostomy closure. The most common methods used for diagnosis were pouchoscopy (31.1%) and gastrograffin enema (28.4%). A definitive non-operative approach was attempted in 48.6%, but was successful in only 10.8% patients overall. Surgical repair was attempted in 89.2% of patients, while 4.5% had pouch excision. Salvage operations (n=63) included sutured or stapled repair of the tip of the J (65%), pouch excision with neo-pouch (25.4%), and pouch disconnection, repair and re-anastomosis (9.5%). Ultimately 10 (13.5%) patients required pouch excision, yielding an overall 5-year pouch survival rate of 86.3%.

LIMITATIONS:

Retrospective review; referral bias may limit the generalizability.

CONCLUSIONS:

Tip of the J-pouch leaks have variable clinical presentations and require a high index of suspicion. Pouch salvage surgery is required in the majority and is associated with a high pouch salvage rate. See Video Abstract at http://links.lww.com/DCR/C50.
Shave biopsy technique and hemostasis pearl
Authors: Twede Katherine Ada , Bui Aimee Kim , Burke Jennifer
Published: November 2022

Nurse practitioners (NPs) are frequently called on to assess and diagnose patients presenting with suspicious or aggravated skin lesions. Performing shave biopsies and removing small neoplasms can be within the scope of a general NP. We offer a thorough review of shave biopsy methods, including required materials, photographic documentation, blade preparation and orientation, and hemostasis techniques. Diagnostic considerations when choosing a shave versus other biopsy techniques are reviewed as is the removal of lesions in cosmetically sensitive areas. Finally, a unique tip to diminish intraprocedure bleeding using aluminum chloride before procedure initiation is presented.
Extracorporeal Membrane Oxygenation Support in COVID-19 Patients: A Propensity Score Analysis
Authors: Abramov Alexey , Su Irene , Agerstrand Cara , Flatley Meaghan , Dubois Richard , Feldhaus Danielle , Stanifer Bryan P. , Sonett Joshua , Brodie Daniel , Lemaitre Philippe
Published: November 2022

Revised guidelines clarify indications for extracorporeal membrane oxygenation (ECMO) support in Coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS). Limited data exist to compare clinical outcomes of COVID-19 ARDS patients to non-COVID-19-related ARDS patients when supported with ECMO. An observational propensity-matched study was performed to compare clinical and ECMO-related complications between COVID-19-related ARDS patients (COVID) and non-COVID-19-related ARDS (Control). COVID- patients cannulated from March 1st, 2020, through June 1st, 2021, were included and matched to patients from the historical cohort at our center from 2012 to 2020 based on age, body mass index (BMI), acute physiology and chronic health evaluation (APACHE) II score, and duration ECMO run. The primary outcome was complications during ECMO therapy. A total of 56 patients were propensity matched 1:1 with a mean age of 40.9 years, BMI 32.1 kg/m2, APACHE II score of 26.6, and duration of ECMO support of 22.6 days. In total 18 COVID-19 patients were observed to have more major bleeding complications (18 vs. 9, p = 0.03). Although not statistically significant, they also had more strokes (6 vs. 3) and required more chest tubes (13 vs. 8). Inpatient mortality was not different. ECMO support in COVID-19 patients is associated with more major bleeding complications, strokes, and chest tube placements. The use of ECMO in patients with COVID-19-related ARDS appears to be associated with an increased risk of complications.
One-Year Outcome of Cardiac Contractility Modulation in Patients With Reduced Ejection Fraction, Atrial Fibrillation, and Previous Resynchronization: A Pilot Study
Authors: Tint Diana , Micu Sorin
Published: November 2022

Background:

After 6 months of therapy, cardiac contractility modulation (CCM) has been shown to improve symptoms, exercise tolerance, and quality of life as well as reduce the rate of hospitalizations in patients with heart failure with reduced left ventricular ejection fraction (HFrEF), but long-term effects data are lacking, with no randomized trial to date.

Study question:

What is the long-term benefit of the CCM device implantation in symptomatic patients with severe, optimally treated HFrEF?

Study design:

We conducted a prospective trial involving patients with symptomatic HFrEF [New York Heart Association (NYHA) Class III or IV, left ventricular ejection fraction (LVEF) ≤35%] who were supported by a CCM device.

Results:

Twenty patients (19 men), aged 66.5 ± 6.9 years, were provided with CCM therapy and followed up for an average duration of 321.7 ± 113.5 days. The etiology of heart failure was ischemic in 16 patients (80%), 9 patients (45%) had atrial fibrillation, 6 patients (30%) had diabetes mellitus, and mean creatinine clearance value was 54.8 ± 13.0 mL/min. Eleven patients (60%) had LVEF ≤25%. Although all the patients had an implanted cardioverter–defibrillator, 6 of them (30%) also had resynchronization therapy. The pharmacological treatment has been optimized in all patients. One year after implantation, the LVEF increased from 24.68% ± 4.5 to 34.6 ± 5 (P < 0.0001), NYHA class improved from 3.2 ± 0.5 to 1.4 ± 0.5 (P < 0.0001), and exercise tolerance evaluated with a 6-Minute Walk Test increased (from 307.9 ± 74.1 m to 567 ± 99.5 m; P < 0.00001). These improvements were largely seen in the first 6 months.

Conclusions:

Over the course of a year, CCM therapy was associated with improved LVEF and NYHA class, as well as significantly better exercise tolerance, even in patients with atrial fibrillation and cardiac resynchronization therapy and did not seem to be associated with additional significant device-related problems.
Comparison of 22C3-PD-L1 Expression Between Paired Tumor Paraffin Blocks of Surgical Resection Specimens of Nonsmall Cell Lung Cancer
Authors: Jiang Li , Zhang Jing , Xu Haimin , Liu Huifang , Wang Chaofu , Chen Xiaoyan
Published: November 2022

In this study, our aim was to evaluate the discordance of programmed cell death ligand 1 (PD-L1) expression between 2 paired paraffin blocks from surgical nonsmall cell lung cancer (NSCLC) specimens, thus providing recommendations for choosing paraffin blocks for PD-L1 immunohistochemistry detection. A total of 460 paired paraffin blocks of surgical NSCLC specimens were analyzed using the 22C3-PD-L1 assay. PD-L1 expression between 2 paired paraffin blocks was calculated using 3 classification schemes, tumor proportion score (TPS)-based 3-level classification and TPS-based binary classification using TPS ≥1% or TPS ≥50% as the cutoff. Clinicopathological characteristics were analyzed for cases with discordant PD-L1 expression. PD-L1 expression in 2 paired paraffin blocks of surgical NSCLC specimens was highly correlated from a single tumor (R
2=0.89) in the overall trend. The overall discordance rates were 10.9%, 7.4%, and 3.5% respectively when using TPS-based 3-level classification or binary classification. No statistical differences were observed in PD-L1 expression discordance rates when patients were stratified by age, sex, smoking status, histologic types, TNM stage, or years of paraffin blocks (P>0.05). The presence of a solid histologic pattern was associated with a higher PD-L1 expression discordance rate in adenocarcinomas (P<0.05). Twenty-five cases with discordant PD-L1 expression were divided into 2 categories: spatial heterogeneity without recognizable morphology difference (76%) and spatial heterogeneity with significantly different morphology (24%). The discordance rate in TPS scores was much higher in cases with different morphology than those without different morphology. One representative paraffin block containing adequate neoplastic tissue may be adequate to determine PD-L1 expression in most of the surgical specimens of NSCLC. In cases that harbored different morphology in different paraffin blocks, the dual-block immunohistochemistry assessment method is recommended due to the intratumoral heterogeneity.
Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines
Authors: Dinsmoor David A. , Usoro Joshua O. , Barka Noah D. , Billstrom Tina M. , Litvak Leonid M. , Poree Lawrence R.
Published: November 2022

Introduction and Objectives:

Unlike conventional dorsal spinal cord stimulation (SCS)—which uses single pulses at a fixed rate—burst SCS uses a fixed-rate, five-pulse stimuli cluster as a treatment for chronic pain; mechanistic explanations suggest burst SCS differentially modulate the medial and lateral pain pathways vs conventional SCS. Neural activation differences between burst and conventional SCS are quantifiable with the spinal-evoked compound action potential (ECAP), an electrical measure of synchronous neural activation.

Methods:

We implanted 7 sheep with a dorsal stimulation lead at T9/T10, a dorsal ECAP sensing lead at T6/T7, and a lead also at T9/T10 but adjacent to the anterolateral system (ALS). Both burst and conventional SCS with stimulation amplitudes up to the visual motor threshold (vMT) were delivered to 3 different dorsal spinal locations, and ECAP thresholds (ECAPTs) were calculated for all combinations. Then, changes in ALS activation were assessed with both types of SCS.

Results:

Evoked compound action potential thresholds and vMTs were significantly higher (P < 0.05) with conventional vs burst SCS, with no statistical difference (P > 0.05) among stimulation sites. However, the vMT−ECAPT window (a proxy for the useable therapeutic dosing range) was significantly wider (P < 0.05) with conventional vs burst SCS. No significant difference (P > 0.05) in ALS activation was noted between conventional and burst SCS.

Conclusion:

When dosed equivalently, no differentially unique change in ALS activation results with burst SCS vs conventional SCS; in addition, sub-ECAPT burst SCS results in no discernable excitability changes in the neural pathways feeding pain relevant supraspinal sites.
Radiation therapy post radical prostatectomy: who, when and why?
Authors: Latorzeff Igor , Le Guevelou Jennifer , Sargos Paul
Published: November 2022

Purpose of review

During decades, adjuvant radiotherapy (ART) has been the standard of care after surgery, based on four randomized clinical trials (RCTs). As early salvage radiotherapy (SRT) recently challenged the ART paradigm, the optimal timing to initiate radiotherapy remains a matter of debate.

Recent findings

Three RCTs evaluated ART or SRT for postprostatectomy patients, with pathological risk factors (Gleason score > 8, pT3, positive margins). The ARTISTIC meta-analysis demonstrated similar 5-year biochemical recurrence-free survival for ART and SRT (89 vs. 88%). Lower rates of late genitourinary toxicity were demonstrated within the SRT arm, favouring early SRT in clinical practice.

The addition of pelvic lymph node radiotherapy recently demonstrated an improvement in freedom from progression within the randomized RTOG 0534 trial, especially for patients with pretreatment prostate serum antigen (PSA) levels more than 0.35 ng/ml. The most appropriate androgen deprivation therapy duration remains a point of controversy.

The SRT approach can be favoured for the vast majority of patients, provided close monitoring of PSA and early treatment in the event of biochemical recurrence. Radiotherapy dose and volumes and ADT use might be correlated to SRT timing (early vs. late). Results from trials including genomic tests and metabolic imaging will probably help to refine these criteria.
Traumatic peripheral nerve injuries: diagnosis and management
Authors: Barnes Stephanie L. , Miller Thomas A. , Simon Neil G.
Published: November 2022

Purpose of review

To review advances in the diagnostic evaluation and management of traumatic peripheral nerve injuries.

Recent findings

Serial multimodal assessment of peripheral nerve injuries facilitates assessment of spontaneous axonal regeneration and selection of appropriate patients for early surgical intervention. Novel surgical and rehabilitative approaches have been developed to complement established strategies, particularly in the area of nerve grafting, targeted rehabilitation strategies and interventions to promote nerve regeneration. However, several management challenges remain, including incomplete reinnervation, traumatic neuroma development, maladaptive central remodeling and management of fatigue, which compromise functional recovery.

Innovative approaches to the assessment and treatment of peripheral nerve injuries hold promise in improving the degree of functional recovery; however, this remains a complex and evolving area.
Neurology education in the era of artificial intelligence
Authors: Kedar Sachin , Khazanchi Deepak
Published: November 2022

Purpose of review

The practice of neurology is undergoing a paradigm shift because of advances in the field of data science, artificial intelligence, and machine learning. To ensure a smooth transition, physicians must have the knowledge and competence to apply these technologies in clinical practice. In this review, we describe physician perception and preparedness, as well as current state for clinical applications of artificial intelligence and machine learning in neurology.

Recent findings

Digital health including artificial intelligence-based/machine learning-based technology has made significant inroads into various aspects of healthcare including neurological care. Surveys of physicians and healthcare stakeholders suggests an overall positive perception about the benefits of artificial intelligence/machine learning in clinical practice. This positive perception is tempered by concerns for lack of knowledge and limited opportunities to build competence in artificial intelligence/machine learning technology. Literature about neurologist's perception and preparedness towards artificial intelligence/machine learning-based technology is scant. There are very few opportunities for physicians particularly neurologists to learn about artificial intelligence/machine learning-based technology.

Neurologists have not been surveyed about their perception and preparedness to adopt artificial intelligence/machine learning-based technology in clinical practice. We propose development of a practical artificial intelligence/machine learning curriculum to enhance neurologists’ competence in these newer technologies.
Clozapine-Induced Fever and Plasma Cytokine Changes in a Patient With Schizophrenia
Authors: Nakamura Masaru , Nagamine Takahiko
Published: November 2022

Introduction

Clozapine-induced fever is frequently documented in the early stages of administration. Fever during clozapine treatment often presents a clinical challenge, because there are no established guideline to decide when fever is the adverse effect. Although the etiology of clozapine-induced fevers remains unknown, evidence has suggested that fever may develop secondarily to a generalized inflammatory response as a manifestation of the immune-modulating effects of clozapine.

Case Presentation

We presented a 59-year-old male patient with a treatment-resistant schizophrenia, who was introduced clozapine for the first time. He became febrile on day 14 at 75 mg/d. He was diagnosed clozapine-induced fever, which was improved by dose reduction on day 27 at 25 mg/d. However, we noticed significant high levels of blood urea nitrogen and serum creatinine on day 29, which resulted in withdrawal of clozapine. Also, we found continuous eosinophilia on day 33. After we provided conservative therapy with appropriate intravenous fluids, his kidney function and eosinophilic counts returned to normal on day 59 and day 53, respectively. The time-sequential changes of levels of interleukin 6 and tumor necrosis factor α suggested that the upregulated cytokines play a role on clozapine-induced fever and subsequent eosinophilia under severe renal failure condition.

Conclusions

To our knowledge, this is the first case presentation of clozapine-induced fever discussing the mechanism, differential diagnosis, and decision making of clozapine treatment focusing on plasma cytokines. If once fever occurs, an extensive medical workup for the fever and a careful systemic medical management should be promptly proceeded to avoid clozapine-associated severe complications.
A Case of Multidrug-Resistant Lance-Adams Syndrome Successfully Treated With Phenobarbital
Authors: Yeniay Süt Nurşah , Yıldırım Miraç , Bektaş Ömer , Kendirli Tanıl , Teber Serap
Published: November 2022

Objective

Lance-Adams syndrome is a rare but devastating disorder characterized by rest, action, and stimulus-sensitive myoclonus after cardiorespiratory arrest. We aimed to present a case of multidrug-resistant Lance-Adams syndrome that was successfully treated with oral phenobarbital therapy.

Method and Results

We report a previously healthy 11-year, 6-month-old boy was referred to our pediatric intensive care unit because of severe hypoxic ischemic brain injury due to sudden cardiorespiratory arrest. On the 15th day of hospitalization, he developed myoclonic jerks involving his limbs, trunk, and eyes. Despite many antiseizure medications in different combinations, myoclonic jerks persisted. Then, phenobarbital was started, and myoclonic jerks disappeared the next day. At the final evaluation, additional phenobarbital treatment was continued for 6 months and the patient remained myoclonus-free during this time.

Conclusions

To the best of our knowledge, this case is the first report describing significant improvement with phenobarbital in a patient with multidrug-resistant Lance-Adams syndrome. We suggest that phenobarbital is an effective option and should be kept in mind in patients with multidrug-resistant Lance-Adams syndrome.
Zobellella iuensis sp. nov., an aerobic denitrifying bacterium isolated from activated sludge
Authors: Li Jiangwei , Hu Anyi , Liang Xiaoxuan , Yang Xiaoyong , Jia Yanwen , Yu Chang-Ping
Published: November 2022

An aerobic denitrifying bacterium, designated as strain CPY4T, was isolated from activated sludge treating urban sewage under alternating aerobic/anaerobic conditions by an enrichment culture technique. Cells of strain CPY4T were Gram-stain-negative, aerobic, long rod-shaped, motile by means of single polar flagellum and capable of aerobic denitrification with citrate as the carbon source. Growth of strain CPY4T was observed at 10–45 °C (optimum, 30–35 °C), at pH 6.0–10.5 (optimum, pH 8.0–8.5) and in 0–5 % NaCl (optimum, 0–3 %; w/v). The 16S rRNA gene sequence of strain CPY4T showed the highest similarity to

Zobellella denitrificans

ZD1T (97.9 %), followed by

Zobellella endophytica

59N8T (97.6 %),

Zobellella aerophila

JC2671T (97.2 %),

Zobellella taiwanensis

ZT1T (97.1 %) and

Zobellella maritima

102-Py4T (96.3 %). Genome comparisons between CPY4T and other

Zobellella

species showed highest digital DNA–DNA hybridization with

Z. denitrificans

ZD1T (43.8 %) and highest average nucleotide identity (ANIb and ANIm) of genome nucleotide sequences with

Z. denitrificans

ZD1T(90.7 and 92 %, respectively). Phylogenetic analysis revealed that strain CPY4T fell within the clade comprising the type strains of

Zobellella

species and formed a phyletic line with them, which was distinct from other members of the family

Aeromonadaceae

. The sole respiratory ubiquinone was quinone 8. The predominant fatty acids (>10 % of the total fatty acids) of strain CPY4T were summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c), summed feature 3 (C16 : 1
 ω6c and/or C16 : 1
 ω7c) and C16 : 0. The genomic DNA G+C content was 62.7 mol %. In the polar lipid profile, diphosphatidylglycerol, phosphatidylglycerol, phosphatidyl ethanolamine, phospholipids and aminolipids were the major compounds. Based on the genotypic and phenotypic data, strain CPY4T represents a novel species of the genus

Zobellella

, for which the name Zobellella iuensis sp. nov. is proposed. The type strain is CPY4T (=JCM 34456T=CGMCC 1.18722T).
Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya
Authors: Imam Zainab O , Nabwera Helen M , Tongo Olukemi O , Andang’o Pauline EA , Abdulkadir Isa , Ezeaka Chinyere V , Ezenwa Beatrice N , Fajolu Iretiola B , Mwangome Martha K , Umoru Dominic D , Akindolire Abimbola E , Otieno Walter , Olwala Macrine , Nalwa Grace M , Talbert Alison W , Abubakar Ismaela , Embleton Nicholas D , Allen Stephen J
Published: November 2022

Background

Preterm (born < 37 weeks’ gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the advancement of feeds among these vulnerable infants in sub-Saharan Africa.

Aim

To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries.

Methods

Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds.

Results

Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.75; 95% CI 1.16 to 2.34; p value <0.001) and the occurrence of respiratory distress (−1.89; −3.27 to −0.5; <0.007) and necrotising enterocolitis (4.59; 1.16 to 7.92; <0.009).

Conclusion

The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve newborn outcomes.
Protein unfolding. Thermodynamic perspectives and unfolding models
Authors: Seelig Joachim , Seelig Anna
Published: November 2022

Protein unfolding is a dynamic cooperative process with many short-lived intermediates. Cooperativity means that similar molecular elements act dependently on each other. The thermodynamics of protein unfolding can be determined with differential scanning calorimetry (DSC). The measurement of the heat capacity provides the temperature profiles of enthalpy, entropy and free energy. The thermodynamics of protein unfolding is completely determined with these thermodynamic properties. We emphasise the model-independent analysis of the heat capacity. The temperature profiles of enthalpy H(T), entropy S(T) and free energy G(T) can be obtained directly by a numerical integration of Cp(T). In evaluating different models for protein unfolding. It is essential to simulate all thermodynamic properties, not only the heat capacity. A chemical equilibrium two-state model is a widely used approximation to protein unfolding. The model assumes a chemical equilibrium between only two protein conformations, the native protein (N) and the unfolded protein (U). The model fits the heat capacity Cp(T) quite well, but fails in simulating the other thermodynamic properties. In this review we propose a modification of the chemical equilibrium two-state model, which removes these inconsistencies. We also propose a new statistical-mechanical two-state model based on a simple, two-parameter partition function Z(T), from which all thermodynamic parameters can be derived. The thermodynamic predictions of the new models are compared to published DSC-experiments obtained with lysozyme, a globular protein, and β-lactoglobulin, a β-barrel protein. Good fits to all thermodynamic properties are obtained. In particular, the models predict a zero free energy for the native protein, which is confirmed experimentally by DSC. This is in contrast to the often-cited chemical equilibrium two-state model, which predict a positive free energy for the native protein. Two-state models use macroscopic fit parameters, the conformational enthalpy and the heat capacity difference between native and unfolded protein. These simulations provide no molecular insight. The review therefore includes a recently published multistate cooperative model based on physicality well-defined molecular parameters only.
Site-specific cancer incidence by race and immigration status in Canada 2006-2015: a population-based data linkage study
Authors: Malagón Talía , Morais Samantha , Tope Parker , El-Zein Mariam , Franco Eduardo L
Published: November 2022

Introduction

The Canadian Cancer Registry does not collect demographic data beyond age and sex, making it hard to monitor health inequalities in cancer incidence in Canada, a country with public healthcare and many immigrants. Using data linkage, we compared site-specific cancer incidence rates by race.

Methods

We used data from the 2006 and 2011 Canadian Census Health and Environment Cohorts (CanCHECs), which are population-based probabilistically linked datasets of 5.9 million respondents of the 2006 Canadian long-form census and 6.5 million respondents of the 2011 National Household Survey. Respondents’ race was self-reported using Indigenous identity and visible minority group identity questions. Respondent data were linked with the Canadian Cancer Registry up to 2015. We calculated age-standardized incidence rate ratios (ASIRR), comparing group-specific rates to the overall population rate with bootstrapped 95% confidence intervals (95%CI). We used negative binomial regressions to adjust rates for socioeconomic variables and assess interactions with immigration status.

Results

The age-standardized cancer incidence rate was lower in almost all non-White racial groups than in White individuals, except for Indigenous peoples who had a similar overall age-standardized cancer incidence rate (ASIRR 0.99, 95%CI 0.97-1.01). Immigrants had substantially lower age-standardized overall cancer incidence rates than non-immigrants (ASIRR 0.83, 95%CI 0.82-0.84). Non-White racial groups generally had significantly lower or equivalent site-specific cancer incidence rates than the overall population, except for stomach, liver, and thyroid cancers and for multiple myeloma. Differences in incidence rates by race persisted even after adjusting for household income, education, and rural residence, with immigration status being an important modifier of cancer risk.

Conclusions

Differences in cancer incidence between racial groups are likely influenced by differences in lifestyles and early life exposures, as well as selection factors for immigration. This suggests a strong role of environment in determining cancer risk and further potential for cancer prevention.
EV Fingerprinting: Resolving extracellular vesicle heterogeneity using multi-parametric flow cytometry
Authors: von Lersner Ariana K. , Fernandes Fabiane C. L. , Ozawa Patricia M. M. , Lima Sierra M. , Vagner Tatyana , Sung Bong Hwan , Wehbe Mohamed , Franze Kai , Wilson John T. , Irish Jonathan M. , Weaver Alissa , Vizio Dolores Di , Zijlstra Andries
Published: November 2022

Mammalian cells release a heterogeneous array of extracellular vesicles (EVs) that impact human biology by contributing to intercellular communication. To resolve EV heterogeneity and define the EV populations associated with specific biological processes, we developed a method named “EV Fingerprinting” that discerns distinct vesicle populations using dimensional reduction of multi-parametric data collected by quantitative single-EV flow cytometry. After validating this method against synthetic standards, the EV Fingerprinting analysis of highly purified EVs enabled a much more granular resolution of biochemically distinct EV populations than previously established methods. The analysis of EVs produced after molecular perturbation of EV biogenesis through ablation of the GTPase Rab27a and overexpression of the tetraspanin CD63 revealed that EV Fingerprinting reflects the molecular state of a cell. Subsequent analysis of human plasma demonstrates the capacity of EV Fingerprinting to resolve EV populations in complex biological samples and detect tumor-cell derived EVs.
RNA sequencing analyses of gene expression by CRISPR/Cas9 knockout of CLL-1 gene in acute myeloid leukemia cells
Authors: Wang Yanyu , Wu Songfang , Yang Jing , Wang ShiLiang , Xiong Hong , Li Shui-Jun
Published: November 2022

CLL-1 has been revealed its potential role in acute myeloid leukemia (AML), however, the underlying mechanisms remain unclear. CRISPR/Cas9 strategy was employed to knock out CLL-1 gene in U937 cells and western-blot was used to validate the success of knock out. CCK8 and Transwell assays were used to detect cells viability and migration, respectively. RNA-sequencing was performed to profile mRNA expression in CLL-1 gene knock-out and wide type U937 cells. A cutoff of 1.5-fold change and false discovery rate (FDR) <0.05 was used to screen differentially expressed genes (DEGs), which were presented by volcano plots and hierarchical cluster heatmap. Protein-protein interaction (PPI) network was constructed by String database and Cytoscape software. Furthermore, hub genes were mined by CytoNCA and MCODE, which were subjected to functional enrichment using R package. Finally, the findings were validated using qRT-PCR and western-blot. The protein level of CLL-1 was significantly lowered, and cell viability and migration were suppressed in knock-out cells compared to wide type. Using RNA-sequencing and bioinformatics analysis, 452 DEGs (179 up-regulated and 273 down-regulated) were obtained, and several important hub genes (such as CCR2, FBXO21, UBB and UBE2C) were filtered out, which were enriched in 132 GO terms and 36 KEGG pathways such as chemokine signaling pathway and ubiquitin mediated proteolysis. A total of 8 representative genes mRNA expressions were validated by qRT-PCR, and the protein levels of 6 genes were confirmed by western-blot. CLL-1 gene might exert its role in AML through modulating genes enriched in multiple functions such as chemokine signaling and ubiquitination. Our results may give us new knowledge of CLL-1 in AML and provide a basis for mining novel targets.
Profiling of chimeric RNAs in human retinal development with retinal organoids
Authors: Wang Wen , Zhang Xiao , Zhao Ning , Xu Ze-Hua , Jin Kangxin , Jin Zi-Bing
Published: November 2022

Chimeric RNAs have been found in both cancer and healthy human cells. They have regulatory effects on human stem/progenitor cell differentiation, stemness maintenance and central nervous system (CNS) development. However, their physiological functions in the retinal development remain unknown. Based on the human embryonic stem cells (hESC)-derived retinal organoids (ROs) spanning from day 0 to day 120, we present the expression atlas of chimeric RNAs throughout the developing ROs. We confirmed the existence of some common chimeric RNAs and also discovered many novel chimeric RNAs during retinal development. We focused on CTNNBIP1-CLSTN1 (CTCL) whose downregulation causes precocious neuronal differentiation and a marked reduction of neural progenitors in human cerebral organoids. Our study found that CTCL also plays a key role in human retinogenesis, CTCL loss-of-function obstructed RO differentiation but prompted the retinal pigment epithelial (RPE) differentiation. Together, this work provides a landscape of chimeric RNAs and reveals evidence for their crucial roles in human retina development.
Cotranslational formation of disulfides guides folding of the SARS COV-2 receptor binding domain
Authors: Bitran Amir , Park Kibum , Serebryany Eugene , Shakhnovich Eugene I.
Published: November 2022

Many secreted proteins contain multiple disulfide bonds. How disulfide formation is coupled to protein folding in the cell remains poorly understood at the molecular level. Here, we combine experiment and simulation to address this question as it pertains to the SARS-CoV-2 receptor binding domain (RBD). We show that, whereas RBD can refold reversibly when its disulfides are intact, their disruption causes misfolding into a nonnative molten-globule state that is highly prone to aggregation and disulfide scrambling. Thus, non-equilibrium mechanisms are needed to ensure disulfides form prior to folding in vivo. Our simulations suggest that co-translational folding may accomplish this, as native disulfide pairs are predicted to form with high probability at intermediate lengths, ultimately committing the RBD to its metastable native state and circumventing nonnative intermediates. This detailed molecular picture of the RBD folding landscape may shed light on SARS-CoV-2 pathology and molecular constraints governing SARS-CoV-2 evolution.
A metabolome-wide Mendelian randomization study prioritizes causal circulating metabolites for multiple sclerosis
Authors: Ge Angela , Sun Yitang , Kiker Thaddaeus , Zhou Yanjiao , Ye Kaixiong
Published: November 2022

Objective

To prioritize circulating metabolites that likely play causal roles in the development of multiple sclerosis (MS).

Methods

Two-sample Mendelian randomization analysis was performed to estimate the causal effects of 571 circulating metabolites on the risk of MS. Genetic instruments for circulating metabolites were obtained from three previous genome-wide association studies (GWAS) of the blood metabolome, while genetic associations with MS were from a large GWAS by the International Multiple Sclerosis Genetics Consortium. The primary analysis was performed with the multiplicative random-effect inverse variance-weighted method, while multiple sensitivity analyses were conducted with the weighted median, weighted mode, MR-Egger, and MR-PRESSO.

Results

A total of 29 metabolites had suggestive evidence of causal associations with MS. Genetically instrumented levels of serine (OR = 1.56, 95% CI = 1.25 – 1.95), lysine (OR = 1.18, 95% CI = 1.01 – 1.38), acetone (OR = 2.45, 95% CI = 1.02 – 5.90), and acetoacetate (OR = 2.47, 95% CI = 1.14 – 5.34) were associated with a higher MS risk. Total cholesterol and phospholipids in large very-low-density lipoprotein were associated with a lower MS risk (OR = 0.83, 95% CI = 0.69 – 1.00; OR = 0.80, 95% CI = 0.68 – 0.95), but risk-increasing associations (OR = 1.20, 95% CI = 1.04 – 1.40; OR = 1.13, 95% CI = 1.00 – 1.28) were observed for the same two lipids in very large high-density lipoprotein.

Conclusions

Our metabolome-wide Mendelian randomization study prioritized a short list of circulating metabolites, such as serine, lysine, acetone, acetoacetate, and lipids, that likely have causal associations with MS.
Differences between robot servers and human servers in brand modernity, brand love and behavioral intentions in the restaurant industry
Authors: Kim Heather Markham , Abbas Jawad , Haq Muhammad Zia Ul , Lee JungHoon (Jay) , Hwang Jinsoo
Published: November 2022

Purpose

This study examined the effect of brand modernity on brand love. In addition, this study investigated how brand love affects behavioral intentions including intentions to use, word-of-mouth and willingness to pay more. Lastly, this study explored the differences between robot servers and human servers in the five concepts mentioned above.

Design/methodology/approach

Data were collected from 300 people who experienced robot servers and from 318 people who experienced human servers.

Findings

The results of data analysis revealed that brand modernity has a positive influence on brand love, which in turn positively affects intentions to use, word-of-mouth and willingness to pay more. Additionally, it was found that there were statistical differences with the mean value of the five concepts based on the type of employee, such as robot servers and human servers.

Originality/value

Unlike prior research, the difference between robot servers and human servers was investigated by focusing more on the brand in this study, and such findings can be considered as important theoretical implications of this study.
Trade barrier decrease and environmental pollution improvement: new evidence from China’s firm-level pollution data
Authors: Chen Dengke
Published: November 2022

Purpose

Trade and environment are essential issues closely related to the development of the national economy and the improvement of people’s livelihood in the new era. The Report to the 19th National Congress of the Communist Party of China (CPC) listed the construction of a strong trading power as an important part of building a modern economic system and pollution prevention and treatment as one of the three key battles to win the decisive victory of building a moderately prosperous society in all respects. However, the relationship between trade and environmental pollution is still very controversial in the existing literature, and there is a paucity of literature on the relationship between trade and environmental pollution based on micro data.

Design/methodology/approach

This paper merged China’s Firm-Level Pollution Database with China’s Industrial Enterprise Database and China’s industry tariff rates. Additionally, by virtue of the quasi-natural experiment of China’s accession to the World Trade Organization (WTO), a difference in difference (DID) model was constructed to alleviate the endogeneity issue.

Findings

According to the results, the trade barrier decrease (trade liberalization) significantly reduces the intensity of SO2 emissions, a major pollutant of enterprises, as the intensity of SO2 emissions decreased 2.16% for each unit decrease of the trade barrier. The analysis of the mechanisms shows that the SO2 emission intensity of enterprises is mainly due to the decrease of enterprises’ pollution emission rather than the decrease of output, and the decrease of enterprises’ pollution emission is mainly caused by the enterprises’ cleaner production process rather than the end treatment of pollution emission. The decrease of coal use intensity is an important mechanism of the decrease of SO2 emission intensity caused by the decrease of trade barriers. Among the technical effects of the change of the trade barrier affecting enterprises’ pollution emission, biased technical change rather than neutral technical change dominates.

Originality/value

The findings of this paper imply that expanding openness can enhance China’s social welfare not only through the economic growth mechanisms identified in the classical literature, but also through environmental improvements. This provides useful policy insights for promoting the construction of a strong trading power and winning the battle against pollution in the new era.
On the theoretical source of the reform of socialist open economy with Chinese characteristics
Authors: Lu Jiang , Zhang Chen
Published: November 2022

Purpose

Some economic theories have influenced the reform of the socialist open economy with Chinese characteristics. As a new practice of socialism, an open economy is not only driven by China’s productivity level and people’s living standards but also regulated by the law of commodity production and value.

Design/methodology/approach

It was popular to participate in economic globalization for most countries in the second half of the 20th century, but not all of them could benefit from it.

Findings

The key to the success of the open-economy reform with Chinese characteristics lies in learning from and innovating the comparative advantage theory, thus forming an organic whole of the open economy, including the core of correctly handling the relationship between the government and the market, the method of gradual reform, the breakthrough point of transforming the mode of economic development, and serving people all the time.

Originality/value

Achieving internal and external coordination through the combination of opening-up and independence is a critical principle of China’s economic opening-up, which not only effectively safeguards national interests but also actively promotes the construction of a new global order.
Ownership, trickle-down effect and shared development: a political economy analysis
Authors: Gai Kaicheng , Zhou Yongsheng
Published: November 2022

Purpose

As an essential part of mainstream Western development economics, the trickle-down theory originates from the behavioral choices and iterations of thought on conflicts of interest in the evolution of remuneration structure in Western countries. The fundamental flaw of the logic of this theory is that it conceals the inherent implication of social systems and the essential characteristics of social structures.

Design/methodology/approach

This paper examines the relationships among economic growth, income distribution and poverty from the perspective of social relations of production – the nature of production relations determines the nature of distribution relations and further determines the essence of trickle-down development, and ownership is the core mechanism for realizing the trickle-down effect.

Findings

The stagnation or smoothness of the trickle-down effect in different economies is essentially subject to the logic of “development for whom”, which is determined by ownership relationship.

Originality/value

To be more specific, “development for capitalists” and “development for the people” indicate two distinctly different economic growth paths. The former starts with private ownership and follows a bottom-up negative trickle-down path that inevitably leads to polarization, while the latter starts with public ownership and follows a top-down positive trickle-down path that will lead to common prosperity in the end.