bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting the Preamble of the European Social Charter: Paper Tiger or Blessing in Disguise?
Authors: Papadopoulos Nikolaos A
Published: July 2021

The European Social Charter has recently received increased attention due to the evolution of its monitoring mechanism and the need to address a multitude of contemporary challenges to socio-economic rights. Although the treaty’s preamble has played a crucial role in the interpretation of substantive provisions and in shaping state obligations, little attention has been paid to the way in which the preamble has defined the fundamental lines of the ‘jurisprudence’ of the Charter’s monitoring body. The European Committee of Social Rights has deduced from the Charter’s preamble several important general principles for the protection of socio-economic rights, on which it grounds its interpretation. This article analyses these principles and evaluates their effects in the relevant practice. The findings suggest that the Charter’s preamble serves different purposes and performs multiple functions in international law, thus challenging the common assumption that human rights treaty preambles are empty phrases of a merely ceremonial nature.
The Kirchhoff plate equation on surfaces: the surface Hellan–Herrmann–Johnson method
Authors: Walker Shawn W
Published: July 2021

We present a mixed finite element method for approximating a fourth-order elliptic partial differential equation (PDE), the Kirchhoff plate equation, on a surface embedded in ${\mathbb {R}}^{3}$, with or without boundary. Error estimates are given in mesh-dependent norms that account for the surface approximation and the approximation of the surface PDE. The method is built on the classic Hellan–Herrmann–Johnson method (for flat domains), and convergence is established for $C^{k+1}$ surfaces, with degree $k$ (Lagrangian, parametrically curved) approximation of the surface, for any $k \geqslant 1$. Mixed boundary conditions are allowed, including clamped, simply-supported and free conditions; if free conditions are present then the surface must be at least $C^{2,1}$. The framework uses tools from differential geometry and is directly related to the seminal work of Dziuk, G. (1988) Finite elements for the Beltrami operator on arbitrary surfaces. Partial Differential Equations and Calculus of Variations, vol. 1357 (S. Hildebrandt & R. Leis eds). Berlin, Heidelberg: Springer, pp. 142–155. for approximating the Laplace–Beltrami equation. The analysis here is the first to handle the full surface Hessian operator directly. Numerical examples are given on nontrivial surfaces that demonstrate our convergence estimates. In addition, we show how the surface biharmonic equation can be solved with this method.
Toward the development of defined microbial therapeutics
Authors: Li Youxian , Honda Kenya
Published: July 2021

The collection of micro-organisms living in the mammalian gastrointestinal tract, termed the gut microbiota, has been shown to have profound impacts on host health and increasingly is regarded as a viable therapeutic target. Clinical studies of fecal microbiota transplantation have demonstrated potential efficacy of microbiota-based therapies for diseases including Clostridioides difficile infections, inflammatory bowel disease, graft-versus-host disease and cancer. However, the lack of understanding of the active ingredients and potential risks of such therapies pose challenges for clinical application. Meanwhile, efforts are being made to identify effector microbes directly associated with a given phenotype, to establish causality and to devise well-characterized microbial therapeutics for clinical use. Strategies based on defined microbial components will likely enhance the potential of microbiota-targeted therapies.
Genetic mutations in adaptive evolution of growth-independent vancomycin-tolerant Staphylococcus aureus
Authors: Liu Pilong , Hao Zehua , Liu Miaomiao , Niu Mingze , Sun Peng , Yan Shunhua , Zhao Lixiu , Zhao Xin
Published: July 2021

Background

Antibiotic tolerance allows bacteria to overcome antibiotic treatment transiently and potentially accelerates the emergence of resistance. However, our understanding of antibiotic tolerance at the genetic level during adaptive evolution of Staphylococcus aureus remains incomplete. We sought to identify the mutated genes and verify the role of these genes in the formation of vancomycin tolerance in S. aureus.

Methods

Vancomycin-susceptible S. aureus strain Newman was used to induce vancomycin-tolerant isolates in vitro by cyclic exposure under a high concentration of vancomycin (20× MIC). WGS and Sanger sequencing were performed to identify the genetic mutations. The function of mutated genes in vancomycin-tolerant isolates were verified by gene complementation. Other phenotypes of vancomycin-tolerant isolates were also determined, including mutation frequency, autolysis, lysostaphin susceptibility, cell wall thickness and cross-tolerance.

Results

A series of vancomycin-tolerant S. aureus (VTSA) strains were isolated and 18 mutated genes were identified by WGS. Among these genes, pbp4, htrA, stp1, pth and NWMN_1068 were confirmed to play roles in VTSA formation. Mutation of mutL promoted the emergence of VTSA. All VTSA showed no changes in growth phenotype. Instead, they exhibited reduced autolysis, decreased lysostaphin susceptibility and thickened cell walls. In addition, all VTSA strains were cross-tolerant to antibiotics targeting cell wall synthesis but not to quinolones and lipopeptides.

Conclusions

Our results demonstrate that genetic mutations are responsible for emergence of phenotypic tolerance and formation of vancomycin tolerance may lie in cell wall changes in S. aureus.
Self-inflicted penetrating chest trauma from solar powered garden light: a case report
Authors: Murray Lewis William , Bennetts Jayme
Published: July 2021

Penetrating chest trauma is associated with significant morbidity and mortality due to direct injury to vital organs located within the thorax. This is a case of a 53-year-old man who presented with a self-inflicted penetrating chest trauma using a solar powered garden light. The light penetrated the left side of his chest resulting in a haemopneumothorax, diaphragmatic perforation and pericardial haematoma. The patient underwent an urgent explorative thoracotomy for the removal of the garden light, repair of the diaphragmatic perforation and wedge resections of the perforated lung parenchyma. Postoperatively, the patient recovered in the intensive care before being transferred to the psychiatric department.
Running for the Runs: Intermittent Intussusception From Vanek Tumor Manifesting as Constipation Improved With Exercise
Authors: Santander Pablo , Bush Allison , Kramer Nicholas , McCarthy John
Published: July 2021

Constipation commonly affects adults and most often results from benign conditions. Certain associated symptoms (e.g., rectal bleeding or weight loss) raise concern for structural pathology and prompt further evaluation. Intussusception uncommonly affects adults and typically presents with abdominal pain and vomiting. Rarely, intussusception manifests with constipation as the primary symptom. We present a case of a patient with new onset constipation who was only able to induce bowel movements after exercising, a compensatory behavior in the setting of recurrent intussusception because of a Vanek tumor.
The impact of physical processes on the estimation of the ages of asteroid families
Authors: Dell’Oro A , Boccenti J , Spoto F , Paolicchi P , Knežević Z
Published: July 2021

One of the methods used to estimate the ages of the asteroid families is based on the interpretation of the distribution of the sizes versus orbital semimajor axes of their members as the result of their post-formation dynamical evolution. The fundamental hypothesis is that the present distribution of the semimajor axes is essentially the product of the Yarkovsky effect. On the other hand, the observable features of the asteroid families can be affected by several physical and dynamical processes. In this paper, we discuss the role of: (1) the initial distribution of the ejection velocities at the time of the primordial break-up event; (2) the possible correlations between the family members ejection direction and the orientation of the rotational axis (which the direction of the Yarkovsky semimajor axis drift depends on); (3) the gravitational reaccumulation of the parent body fragments during the ballistic phase of the formation process; and (4) the collisional re-orientation of the spin axes during the post-formation evolution phase. We show how each of these mechanisms affects the determination of the ages of the asteroid families, and what additional information can be inferred regarding some aspects of the collisional evolution of the rotation axes.
Why structure and chain length matter: on the biological significance underlying the structural heterogeneity of poly(ADP-ribose)
Authors: Reber Julia M , Mangerich Aswin
Published: July 2021

Poly(ADP-ribosyl)ation (PARylation) is a multifaceted post-translational modification, carried out by poly(ADP-ribosyl)transferases (poly-ARTs, PARPs), which play essential roles in (patho-) physiology, as well as cancer therapy. Using NAD+ as a substrate, acceptors, such as proteins and nucleic acids, can be modified with either single ADP-ribose units or polymers, varying considerably in length and branching. Recently, the importance of PAR structural heterogeneity with regards to chain length and branching came into focus. Here, we provide a concise overview on the current knowledge of the biochemical and physiological significance of such differently structured PAR. There is increasing evidence revealing that PAR’s structural diversity influences the binding characteristics of its readers, PAR catabolism, and the dynamics of biomolecular condensates. Thereby, it shapes various cellular processes, such as DNA damage response and cell cycle regulation. Contrary to the knowledge on the consequences of PAR’s structural diversity, insight into its determinants is just emerging, pointing to specific roles of different PARP members and accessory factors. In the future, it will be interesting to study the interplay with other post-translational modifications, the contribution of natural PARP variants, and the regulatory role of accessory molecules. This has the exciting potential for new therapeutic approaches, with the targeted modulation and tuning of PARPs’ enzymatic functions, rather than their complete inhibition, as a central premise.
COVID-19-associated mucormycosis presenting to the Emergency Department—an observational study of 70 patients
Authors: Ramaswami A , Sahu A K , Kumar A , Suresh S , Nair A , Gupta D , Chouhan R , Bhat R , Mathew R , Majeed J A , Aggarwal P , Nayer J , Ekka M , Thakar A , Singh G , Xess I , Wig N
Published: July 2021

Background

Mucormycosis (MM) is a deadly opportunistic fungal infection and a large surge in COVID-19-associated mucormycosis (CAM) is occurring in India.

Aim

Our aim was to delineate the clinico-epidemiological profile and identify risk factors of CAM patients presenting to the Emergency Department (ED).

Design

This was a retrospective, single-centre, observational study.

Methods

We included patients who presented with clinical features or diagnosed MM and who were previously treated for COVID-19 in last 3 months of presentation (recent COVID-19) or currently being treated for COVID-19 (active COVID-19). Information regarding clinical features of CAM, possible risk factors, examination findings, diagnostic workup including imaging and treatment details were collected.

Results

Seventy CAM patients (median age: 44.5 years, 60% males) with active (75.7%) or recent COVID-19 (24.3%) who presented to the ED in between 6 May 2021 and 1 June 2021, were included. A median duration of 20 days (interquartile range: 13.5–25) was present between the onset of COVID-19 symptoms and the onset of CAM symptoms. Ninety-three percent patients had at least one risk factor. Most common risk factors were diabetes mellitus (70%) and steroid use for COVID-19 disease (70%). After clinical, microbiological and radiological workup, final diagnosis of rhino-orbital CAM was made in most patients (68.6%). Systemic antifungals were started in the ED and urgent surgical debridement was planned.

Conclusion

COVID-19 infection along with its medical management have increased patient susceptibility to MM.
Rapid Radiation and Rampant Reticulation: Phylogenomics of South AmericanLiolaemusLizards
Authors: Esquerré Damien , Keogh J Scott , Demangel Diego , Morando Mariana , Avila Luciano J , Sites Jack W , Ferri-Yáñez Francisco , Leaché Adam D
Published: July 2021

Understanding the factors that cause heterogeneity among gene trees can increase the accuracy of species trees. Discordant signals across the genome are commonly produced by incomplete lineage sorting (ILS) and introgression, which in turn can result in reticulate evolution. Species tree inference using the multispecies coalescent is designed to deal with ILS and is robust to low levels of introgression, but extensive introgression violates the fundamental assumption that relationships are strictly bifurcating. In this study, we explore the phylogenomics of the iconic Liolaemus subgenus of South American lizards, a group of over 100 species mostly distributed in and around the Andes mountains. Using mitochondrial DNA (mtDNA) and genome-wide restriction site-associated DNA sequencing (RADseq; nDNA hereafter), we inferred a time-calibrated mtDNA gene tree, nDNA species trees, and phylogenetic networks. We found high levels of discordance between mtDNA and nDNA, which we attribute in part to extensive ILS resulting from rapid diversification. These data also reveal extensive and deep introgression, which combined with rapid diversification, explain the high level of phylogenetic discordance. We discuss these findings in the context of Andean orogeny and glacial cycles that fragmented, expanded, and contracted species distributions. Finally, we use the new phylogeny to resolve long-standing taxonomic issues in one of the most studied lizard groups in the New World.[Andes; ddRADSeq; introgression; lizards; mtDNA; reptiles; SNPs.]
Consensus-Driven Priorities for Firearm Injury Education Among Medical Professionals
Authors: Hoops Katherine , Fahimi Jahan , Khoeur Lina , Studenmund Christine , Barber Catherine , Barnhorst Amy , Betz Marian E. , Crifasi Cassandra K. , Davis John A. , Dewispelaere William , Fisher Lynn , Howard Patricia K. , Ketterer Andrew , Marcolini Evie , Nestadt Paul S. , Rozel John , Simonetti Joseph A. , Spitzer Sarabeth , Victoroff Michael , Williams Brian H. , Howley Lisa , Ranney Megan L.
Published: July 2021

Purpose

Firearm injury is a leading cause of morbidity and mortality in the United States. However, many medical professionals currently receive minimal or no education on firearm injury or its prevention. The authors sought to convene a diverse group of national experts in firearm injury epidemiology, injury prevention, and medical education to develop consensus on priorities to inform the creation of learning objectives and curricula for firearm injury education for medical professionals.

Method

In 2019, the authors convened an advisory group that was geographically, demographically, and professionally diverse, composed of 33 clinicians, researchers, and educators from across the United States. They used the nominal group technique to achieve consensus on priorities for health professions education on firearm injury. The process involved an initial idea-generating phase, followed by a round-robin sharing of ideas and further idea generation, facilitated discussion and clarification, and the ranking of ideas to generate a prioritized list.

Results

This report provides the first national consensus guidelines on firearm injury education for medical professionals. These priorities include a set of crosscutting, basic, and advanced learning objectives applicable to all contexts of firearm injury and all medical disciplines, specialties, and levels of training. They focus on 7 contextual categories that had previously been identified in the literature: 1 category of general priorities applicable to all contexts and 6 categories of specific contexts, including intimate partner violence, mass violence, officer-involved shootings, peer (nonpartner) violence, suicide, and unintentional injury.

Conclusions

Robust, data- and consensus-driven priorities for health professions education on firearm injury create a pathway to clinician competence and self-efficacy. With an improved foundation for curriculum development and educational program-building, clinicians will be better informed to engage in a host of firearm injury prevention initiatives both at the bedside and in their communities.
Improving Formative Feedback in the Operating Room Setting: Developing and Implementing an Initiative to Improve Feedback Quality and Culture
Authors: Onuoha Onyi , Heins Sarah J. , Clapp Justin T. , Muralidharan Madhavi , Baranov Dimitry Y. , Fleisher Lee A. , Gordon Emily K.B.
Published: July 2021

Problem

Formative feedback, given in an ongoing fashion during the learning process, is fundamental to clinical education. However, dissatisfaction with formative feedback among residents is common. Difficulties with formative feedback are intensified in the operating room (OR) setting due to fast pace, space limitations, and frequent rotation of residents and attendings.

Approach

In the anesthesiology and critical care department at the University of Pennsylvania Perelman School of Medicine, the authors launched the Feedback Moment initiative from January 2018 to May 2018 in which 24 first-year residents and attendings were given a short series of prompts designed to facilitate regular, high-quality formative feedback. The authors conducted semistructured interviews with residents before and after the initiative to evaluate its impact.

Outcomes

In baseline interviews, 18 participating residents stressed the importance of formative feedback but described feeling unsure of their performance due to lack of ongoing constructive input from attendings. They felt hesitant to approach attendings for feedback due to a desire not to interrupt OR workflow or appear incompetent. In follow-up interviews, residents described the initiative as helping to normalize constructive formative feedback but difficult to execute regularly due to OR workflow issues and frequent rotation of attendings with varying approaches.

Next Steps

Challenges faced by participants in this initiative highlight several considerations for effective OR-based formative feedback. Alternative timings for initiating feedback must be considered in light of the hectic nature of the OR workflow. Residents should be equipped with the skills necessary to adapt to varying practice patterns and frequent rotation between attendings, while attendings should be trained to provide a clear rationale for constructive feedback that allows residents to quickly adapt to practice variation. Finally, establishing clear goals among resident–attending pairs is critical to ensuring that formative feedback given in necessarily brief sessions is focused and productive.
The More the Merrier: Integrating Multiple Models of Skeletal Maturity Improves the Accuracy of Growth Prediction
Authors: Munger Alana M. , Yu Kristin E. , Li Don T. , Furdock Ryan J. , Boeyer Melanie E. , Duren Dana L. , Weber David R. , Cooperman Daniel R.
Published: July 2021

Background:

Multiple systems using radiographic skeletal markers to measure development have been described, including the Greulich and Pyle Atlas (GP), the Fels Method (Fels), and the Sanders Hand Classification (Sanders). The purpose of this study was to quantitatively assess whether the integration of skeletal maturity assessment methods and demographic variables improves the accuracy of pediatric growth predictions over the use of skeletal markers or chronologic age alone.

Methods:

The Brush Inquiry contains prospectively collected longitudinal data on children who lived in Cleveland, Ohio between 1926 and 1942. A total of 16 boys and 29 girls were selected for study. All had age, height, and an anteroposterior radiograph of the hand at each of 3 visits. Those visits occurred at 85%, 90%, and 95% of final height. We determined the growth completed at each visit by dividing the height observed by the final height at skeletal maturity. Boys and girls were analyzed separately using chronologic age, height, GP, Fels, and Sanders. The residual difference between the height predicted and actual height, as well as the SD of the prediction error of the cohort at each time point was calculated. To account for multiple visits from each subject, all linear models were produced using the generalized estimating equations (GEEs) procedure.

Results:

For boys, age, GP, and Fels performed similarly in predicting growth remaining at all 3 time points. For girls, age, GP, and Fels performed similarly in predicting growth remaining at the 85% and 95% time points; however, the Fels Method demonstrated improved performance at the 90% time point compared with chronologic age (P=0.0076) and GP alone (P=0.0155). For both boys and girls, the most accurate multivariate GEE model with the lowest SD of prediction error integrated Fels, age, GP, Sanders, and height.

Conclusions:

The most accurate multivariate GEE model of growth prediction for both boys and girls integrated Fels, age, GP, Sanders, and height. When calculating the amount of growth remaining, it is prudent to integrate multiple systems for greater predictive accuracy.

Level of Evidence:

Level III.
Dressing Techniques in Percutaneous Toe Surgery
Authors: Michels Frederick , Malagelada Francesc
Published: July 2021

Percutaneous techniques are becoming increasingly popular in forefoot surgery. In percutaneous toe corrections, usually, no hardware is used. The hardware-free technique avoids any hardware-related complications, but relies highly on the effect of the dressing to keep the foot in the desirable corrected position while healing occurs. The first postoperative dressing is applied by the surgeon. A combination of adhesive taping, sterile gauzes, and an elastic cohesive bandage is used for the first 10 to 14 days. The technique is tailored to the surgical procedure performed and aimed at correcting the preoperative deformity. For the next phase of healing, different bandage techniques can be used. Customized elastic taping is helpful to guide toe position. Alternatively, orthodigital splints can be used. Surgeons should master several bandage techniques. This allows them to choose the best technique depending on the situation. Often, the bandage techniques should be modified to the preoperative situation, the surgical technique, the deformity, and the correction achieved.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Prostaglandin D2 synthase/prostaglandin D2/TWIST2 signaling inhibits breast cancer proliferation
Authors: Pan Jun , Zhang Leyi , Huang Jian
Published: July 2021

Though the past few years have witnessed exciting achievements in targeted and immunotherapeutic treatments of all breast cancer subtypes, yet the decline in breast cancer mortality has been slowed, urging the need for further expanding options of high-quality treatments. Prostaglandin D2 synthase (PTGDS)/prostaglandin D2 (PGD2) play important roles in a variety of cancer types and show tissue-specificity, however, there are limited relevant reports in breast cancer. Therefore, the aims of the present study were to investigate the effects of PTGDS/PGD2 in breast cancer by large-scale bioinformatic analysis and in vitro experiments conducted on human breast cancer cell lines. Results of our study indicated that patients with high levels of PTGDS expression showed a reduced potential of tumor proliferation. PGD2 treatment significantly inhibited the proliferation and migration of breast cancer cells, which was mediated by the reduced expression of TWIST2. Overexpression of TWIST2 reversed the inhibitory effects of PGD2 on breast cancer cell proliferation. These results provided the novel evidence that PTGDS may play a significant role in modulating breast cancer growth, with implications for its potential use in treating breast cancer.
Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorder or Primary Cutaneous Marginal Zone B-Cell Lymphoma? Two Distinct Entities With Overlapping Histopathological Features
Authors: Bakr Farrah , Wain E. Mary , Barlow Richard , Robson Alistair
Published: July 2021

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder and primary cutaneous marginal zone B-cell lymphoma are 2 distinct entities with several overlapping features which can result in diagnostic uncertainty. Clinically, they both follow an indolent course and present with solitary or multiple papules or nodules. Histologically, they are characterized by polymorphous dermal infiltrates rich in mixed populations of B cells and T cells, often in similar proportions. The histological hallmark of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is the presence of follicular T-helper cells within the infiltrate and has historically been used as a marker for differentiating between the 2 conditions. However, there is now mounting evidence that follicular T-helper cells are also seen in primary cutaneous marginal zone B-cell lymphoma and nodal marginal zone lymphoma. The 2 cases presented herein caused diagnostic uncertainty because they displayed appreciable features of both conditions. We discuss the potential mechanisms behind these overlapping histopathological features and hypothesize a model that explores the idea of a collective organoid response to an antigenic stimulus.
Sustained SBP control and long-term nursing home admission among Medicare beneficiaries
Authors: Bowling C. Barrett , Sloane Richard , Pieper Carl , Luciano Alison , Davis Barry R. , Simpson Lara M. , Einhorn Paula T. , Oparil Suzanne , Muntner Paul
Published: July 2021

Objectives:

Sustaining SBP control reduces the risk for cardiovascular events that impair function but its association with nursing home admission has not been well studied.

Methods:

We conducted an analysis of sustained SBP control and long-term nursing home admissions using data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims restricted to participants with fee-for-service coverage, at least eight study visits with SBP measurements, who were not living in a nursing home during a 48-month baseline BP assessment period (n = 6557). Sustained SBP control was defined as less than 140 mmHg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Nursing home admissions were identified using the Medicare Long Term Care Minimum Data Set.

Results:

The mean age of participants was 73.8 years and 44.3% were men. Over a median follow-up of 9.2 years, 844 participants (12.8%) had a nursing home admission. Rates of nursing home admission per 100 person-years were 16.3 for participants with SBP control at less than 50%, 14.1 at 50% to less than 75%, 7.8 at 75% to less than 100%, and 5.3 at 100% of visits. Compared with those with sustained SBP control at less than 50% of visits, hazard ratios (95% confidence intervals) for nursing home admission were 0.79 (0.66–0.93), 0.70 (0.58–0.84), and 0.57 (0.44–0.74) among participants with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively.

Conclusion:

Among Medicare beneficiaries in ALLHAT, sustained SBP control was associated with a lower risk of long-term nursing home admission.
The association of SBP with mortality in patients with stage 1–4 chronic kidney disease
Authors: Zhuo Min , Yang Danwen , Goldfarb-Rumyantzev Alexander , Brown Robert S.
Published: July 2021

Objectives:

Hypertension is a risk factor for chronic kidney disease (CKD) progression and mortality. However, the optimal blood pressure associated with decreased mortality in each stage of CKD remains uncertain.

Methods:

In this retrospective cohort study, we included 13 414 individuals with CKD stages 1-4 from NHANES general population datasets from 1999 to 2004 followed to 31 December 2010. Multivariate analysis and Kaplan--Meier curves were used to assess SBP and risk factors associated with overall mortality in each CKD stage.

Results:

In these individuals with death rates of 9, 12, 30 and 54% in baseline CKD stages 1 through 4, respectively, SBP less than 100 mmHg was associated with significantly increased mortality adjusted for age, sex and race in stages 2,3,4. After excluding less than 100 mmHg, as a continuous variable, higher SBP is associated with fully adjusted increased mortality risk in those on or not on antihypertensive medication (hazard ratio 1.006, P = 0.0006 and hazard ratio 1.006 per mmHg, P < 0.0001, respectively). In those on antihypertensive medication, SBP less than 100 mmHg or in each 20 mmHg categorical group more than 120 mmHg is associated with an adjusted risk of increased mortality. Increasing age, men, smoking, diabetes and comorbidities are associated with increased mortality risk.

Conclusion:

For patients with CKD stages 1–4, the divergence of SBP above or below 100–120 mmHg was found to be associated with higher all-cause mortality, especially in those patients on antihypertensive medication. These findings support the recent guideline of an optimal target goal SBP of 100–120 mmHg in patients with CKD stages 1–4.
The Novel Oral BET-CBP/p300 Dual Inhibitor NEO2734 Is Highly Effective in Eradicating Acute Myeloid Leukemia Blasts and Stem/Progenitor Cells
Authors: van Gils Noortje , Martiañez Canales Tania , Vermue Eline , Rutten Arjo , Denkers Fedor , van der Deure Tiem , Ossenkoppele Gert J. , Giles Francis , Smit Linda
Published: July 2021

Acute myeloid leukemia (AML) is a disease characterized by transcriptional dysregulation that results in a block in differentiation and aberrant self-renewal. Inhibitors directed to epigenetic modifiers, aiming at transcriptional reprogramming of AML cells, are currently in clinical trials for AML patients. Several of these inhibitors target bromodomain and extraterminal domain (BET) proteins, cyclic AMP response binding protein-binding protein (CBP), and the E1A-interacting protein of 300 kDa (p300), affecting histone acetylation. Unfortunately, single epigenetic inhibitors showed limited efficacy due to appearance of resistance and lack of effective eradication of leukemic stem cells. Here, we describe the efficacy of 2 novel, orally available inhibitors targeting both the BET and CBP/p300 proteins, NEO1132 and NEO2734, in primary AML. NEO2734 and NEO1132 efficiently reduced the viability of AML cell lines and primary AML cells by inducing apoptosis. Importantly, both NEO drugs eliminated leukemic stem/progenitor cells from AML patient samples, and NEO2734 increased the effectiveness of combination chemotherapy treatment in an in vivo AML patient-derived mouse model. Thus, dual inhibition of BET and CBP/p300 using NEO2734 is a promising therapeutic strategy for AML patients, making it a focus for clinical translation.
Automated deep learning in ophthalmology: AI that can build AI
Authors: O’Byrne Ciara , Abbas Abdallah , Korot Edward , Keane Pearse A.
Published: July 2021

Purpose of review

The purpose of this review is to describe the current status of automated deep learning in healthcare and to explore and detail the development of these models using commercially available platforms. We highlight key studies demonstrating the effectiveness of this technique and discuss current challenges and future directions of automated deep learning.

Recent findings

There are several commercially available automated deep learning platforms. Although specific features differ between platforms, they utilise the common approach of supervised learning. Ophthalmology is an exemplar speciality in the area, with a number of recent proof-of-concept studies exploring classification of retinal fundus photographs, optical coherence tomography images and indocyanine green angiography images. Automated deep learning has also demonstrated impressive results in other specialities such as dermatology, radiology and histopathology.

Automated deep learning allows users without coding expertise to develop deep learning algorithms. It is rapidly establishing itself as a valuable tool for those with limited technical experience. Despite residual challenges, it offers considerable potential in the future of patient management, clinical research and medical education.

Video abstract

http://links.lww.com/COOP/A44
Peripheral Venous Catheter-related Bloodstream Infections in Hospitalized Children
Authors: Berger Itay , Cohen Tal , Rahmani Eyal , Levy Itzhak , Lowenthal Alexander , Levinsky Yoel , Goldberg Lotem , Marcus Nufar , Kropach Nesia , Ben-Zvi Haim , Chodik Gabriel , Ashkenazi-Hoffnung Liat , Scheuerman Oded
Published: July 2021

Background:

Peripheral venous catheter (PVC) is the most used vascular access device in medicine, allowing administration of intravenous fluids and medications. Known complications associated with PVC include extravasation, phlebitis and rarely bloodstream infection (BSI). Data regarding PVC-related BSI in children are lacking. Our aim was to evaluate the epidemiology, clinical and microbiologic characteristics of pediatric inpatients with PVC-related BSI.

Methods:

A retrospective study was conducted in a pediatric tertiary care center. Children with BSI, admitted to general pediatric departments during 2010–2019, were identified and their medical records examined. Patients with BSI and phlebitis were further characterized and included in the analysis. We excluded patients with central venous catheters, other identified source of infection and with BSI upon admission. Data collected included patients’ demographics and clinical and microbiologic characteristics.

Results:

Twenty-seven children with PVC-related BSI were identified and included in the study, consisting of 0.2% of the total BSI cases. Patient’s median age was 24 (range, 1.5–213) months, 14/27 (52%) were female and 6 (22%) were previously healthy while 21 (78%) had prior medical conditions. Sixteen (59.3%) patients had Gram-negative BSI and 6 (22.2%) Gram-positive bacteria. Polymicrobial infection occurred in 4 (14.8%) patients and Candida albicans in 1 (3.7%) patient. The most common isolated bacteria were Klebsiella spp and Staphylococcus aureus. Longer dwell-time was a predictor of Gram-negative bacteria.

Conclusions:

PVC-related BSI due to Gram-negative bacteria was more common than to Gram-positive bacteria. Clinicians should consider an initial broad-spectrum antibiotic coverage for PVC-related BSI in hospitalized pediatric patients.
Can placebo and nocebo effects generalize within pain modalities and across somatosensory sensations?
Authors: Weng Lingling , Peerdeman Kaya J. , Della Porta Delia , van Laarhoven Antoinette I.M. , Evers Andrea W.M.
Published: July 2021

Abstract

Pain and other somatosensory sensations, such as itch, can be effectively decreased by placebo effects and increased by nocebo effects. There are indications that placebo effects on pain generalize to other sensations and that nocebo effects generalize within itch modalities. However, it has not yet been investigated whether learned effects can generalize within pain stimulus modalities or from pain to itch. Our aims were to test whether placebo and nocebo effects can generalize within pain modalities, ie, from heat pain to pressure pain, and across somatosensory sensations with psychophysiological similarities, ie, from heat pain to cowhage-evoked itch. For this purpose, 65 healthy participants were randomized to either a placebo or nocebo group. All participants first underwent a conditioning and verbal suggestion procedure with heat pain stimuli. Subsequently, responses to heat pain, pressure pain, and cowhage-evoked itch stimuli were tested. Results showed altered levels of heat and pressure pain with the conditioned cue in both placebo and nocebo groups in the expected directions, but no significant difference in itch in both groups. In conclusion, placebo and nocebo effects on pain may generalize within but not across stimulus modalities. This study provides a novel perspective on the role that response generalization plays in physical symptoms.
Right ventricular contractility decreases during exercise in patients with non-advanced idiopathic pulmonary fibrosis
Authors: Cobra Sandra de Barros , Rodrigues Marcelo Palmeira , de Melo Felipe Xavier , Ferreira Nathali Mireise Costa , Melo-Silva César Augusto
Published: July 2021

Early right ventricular dysfunction in patients with non-advanced idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. Thus, we aimed to assess right ventricular functions in IPF patients and controls by speckle-tracking strain echocardiography at rest and peak exercise.

We screened 116 IPF patients from February to August 2019 to include 20 patients with no history of oxygen therapy, peripheral saturation levels ≥92% at rest, Gender-Age-Physiology Index score ≤5, and modified Medical Research Council score ≤3. Additionally, we enrolled 10 matched controls. Transthoracic echocardiography images were acquired at rest and during a cardiopulmonary exercise test. We analyzed 2-dimensional echocardiographic parameters and right ventricular function using the global longitudinal strain assessed by the 2-dimensional speckle-tracking technique.

In the control group, we found normal values of right ventricle longitudinal strain (RVLS) at rest and at peak exercise, the latter being much more negative (−23.6 ± 2.2% and −26.8 ± 3.1%, respectively; P < .001). By contrast, RVLS values in the IPF group increased from −21.1 ± 3.8% at rest to −17.0 ± 4.5% at peak exercise (P < .001). The exercise revealed a difference between the 2 groups as the mean RVLS values moved during peak exercise in opposite directions. Patients with IPF got worse, whereas control patients presented improved right ventricular contractility.

Right ventricular dysfunction was unveiled by speckle-tracking echocardiography during exercise in non-advanced IPF patients. We suggest that this reflects an inadequate right ventricular-arterial coupling decreasing the right ventricular longitudinal contraction during exercise in these patients. This parameter may be useful as an early index of suspected pulmonary hypertension.
Relationship between quantitative contrast-enhanced ultrasonography parameters and angiogenesis in primary small hepatocellular carcinoma
Authors: Deng Shuhao , Jiang Quan , Wang Yongbing , Lu Xin , Zhang Yuan
Published: July 2021

To analyze the correlation between quantitative contrast-enhanced ultrasonography (CEUS) parameters and angiogenesis in primary small hepatocellular carcinoma (sHCC) with varying degrees of differentiation.

According to varying degrees of differentiation, a total of 90 primary sHCC patients admitted to our hospital from July 2018 to January 2020 were selected and divided into poorly differentiated group (24 cases), moderately differentiated group (31 cases), and highly differentiated group (35 cases). All patients received real-time CEUS before surgery. The tumor diameter, microvascular morphology, grading of color blood flow, contrast-enhanced performance in different phases, quantitative CEUS parameters, expression of angiogenesis-related genes, and microvessel density (MVD) were compared among the 3 groups. The correlation between quantitative parameters of CEUS and angiogenesis indexes was analyzed by Spearman rank correlation analysis.

Spearman rank correlation analysis showed that vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor receptor (EGFR), and angiopoietin-2 (Ang-2) expression and MVD were negatively correlated with the time to peak (TTP), wash-out time, and peak accelerating time (PAT) (r < 0, P < .05), and were positively correlated with enhancing slope rate (ESR) and peak intensity increasing rate (PIIR) (r > 0, P < .05).

CEUS is able to identify varying degrees of differentiation in primary sHCC, and the quantitative CEUS parameters are closely related to angiogenesis.
Identification of endometriosis-associated genes and pathways based on bioinformatic analysis
Authors: Wang Ting , Jiang Ruoan , Yao Yingsha , Qian Linhua , Zhao Yu , Huang Xiufeng
Published: July 2021

Endometriosis is associated with dysmenorrhea, chronic pelvic pain, and infertility. The specific mechanism of endometriosis remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of endometriosis.

The gene expression profiles of GSE25628, GSE5108, and GSE7305 were downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using GEO2R. The database for annotation, visualization, and integrated discovery (DAVID) was utilized to analyze the functional enrichment, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using search tool for the retrieval of interacting genes and cytoscape.

A total of 119 common differentially expressed genes were extracted, consisting of 51 downregulated genes and 68 upregulated genes. The enriched functions and pathways of the DEGs and hub genes include DNA strand separation, cellular proliferation, degradation of the extracellular matrix, encoding of smooth muscle myosin as a major contractile protein, exiting the proliferative cycle and entering quiescence, growth regulation, and implication in a wide variety of biological processes.

A bioinformatics approach combined with cell experiments in this study revealed that identifying DEGs and hub genes leads to better understanding of the molecular mechanisms underlying the progression of endometriosis, and efficient biomarkers underlying this pathway need to be further investigated.
Prognostic values of procalcitonin and platelet in the patient with urosepsis
Authors: Jiang Ling , Lin Shao-Hua , Wang Jun , Chu Cun-Kun
Published: July 2021

Background:

The patient suffering from urinary sepsis is often accompanied by elevated serum procalcitonin (PCT) levels and a decline in the average platelet count (PLT), which could result in a poor prognosis. This study aimed to evaluate the value of PCT and PLT in determining the severity of urinary sepsis.

Methods:

A total of 120 urosepsis patients enrolled were divided into a survival group and a death group, respectively, according to their status within 14 days after admission. Changes in PCT and PLT levels between the 2 groups were compared at different time points. A receiver operating characteristic (ROC) curve was eventually obtained to predict the prognostic value of PCT and PLT.

Results:

The PCT levels in the survival group declined gradually after admission, and the PLT decreased at first but increased rapidly in subsequence. The PCT level in the death group, however, declined in a flat-slope trend or was hardly noticeable together with the number of PLT reduced significantly. In particular, it is on the 3rd day that PCT tended to positively correlate with acute physiological and chronic health score II (APACHE II) score (r = 0.730, P < .05), but negatively with PLT (r = 0.472, P < .05). The APACHE II score and PLT (r = 0.612, P < .05) were also negatively correlated with each other. As indicated by the ROC curve, the PCT level on the 3rd day after admission was of great value for the clinical mortality prognosis, and the area under the curve was 0.858. Moreover, PLT also has a high predictive value for prognosis. Area under the curve is 0.951. When the PLT was more than 51 × 109 /L, the sensitivity was up to 90%, and the specificity was 90%.

Conclusion:

PLT and PCT levels are closely related to the APACHE II score, which could indicate the severity of urosepsis in patients. The contribution of this study was to confirm that dynamic monitoring of the changes in PCT and PLT helps determine the prognosis of urosepsis patients.
Relationship among affective commitment, occupational stressors, and calling of psychiatrists in Shanghai
Authors: Lin Xiao , Zhu Yuncheng , Wang Chao , Wang Fang
Published: July 2021

The aim of the study is to investigate the levels of affective commitment, occupational stressors and calling in psychiatrists in Shanghai and try to find the relationship among 3 variables in the participants.

We enrolled 81 participants using a survey with a combination of demographic information, affective part of organizational commitment questionnaire, portion of the scale for occupational stressors on clinicians and the calling and vocation questionnaire. Correlation analysis and multiple linear regression analysis were applied to probe into the relationship among the three variables. t Test and nonparametric test were utilized to compare the differences between the groups of individuals who were divided according to the demographic information.

The mean score of the affective commitment, occupational stressors and calling of Shanghai psychiatrists were all at a moderate level. The scores in affective commitment had a significantly negative relationship with that of the occupational stressors, especially in the respect of organization and management, occupational interest, and development of work. Whereas the scores of calling revealed a remarkably positive connection with affective commitment. In addition, demographic groups under comparison, individuals who were >35 years’ old, male, or have worked for >10 years are more likely to suffer from higher occupational development and interpersonal relationship stress.

We found that the levels of affective commitment, occupational stressors and calling in psychiatrists in Shanghai were all moderate. These people who were men, >35 years’ old, and had >10 years of work experiences had suffered from higher levels of occupational stressors, especially occupational development and interpersonal relationship stress. The affective commitment was positively correlated to the calling while negatively associated to the occupational stressors in Shanghai psychiatrists. For stronger bond for the psychiatrists, strengthen the calling and lessen the occupational stressors are required. These results provide some ideas for enhancing the occupational commitment of psychiatrists and conducting psychological interventions in a timely manner henceforth more effectively.