bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and characterizations of sugar-glass nanoparticles mediated protein delivery system for tissue engineering application
Authors: Pal Aniruddha , Vel Rathina , Rahaman Sk Hasanur , Sengupta Somoshree , Bodhak Subhadip
Published: June 2022

The present work focuses on the synthesis and characterization of a sugar-glass nanoparticle (SGnP) based reservoir type protein delivery system pertinent to tissue engineering applications. The SGnP nanocarriers were prepared via inverse micelle of sodium bis(2-ethylhexyl) sulfosuccinate based on an anionic surfactant and subsequent flash-freezing technique. Initially, a total of five different grades of protein-free SGnPs have been prepared to examine the effects of systematic changes in starting concentrations of the aqueous phase, organic solvent, the molar ratio of water, and surfactant in controlling the size, shape, and uniformity of micelles. Evidently, the Fourier transform infrared (FTIR) and scanning electron microscope (SEM) results confirmed that the SGnP can be successfully prepared. Subsequently, SGnP based protein depot has been validated using bovine serum albumin (BSA), horseradish peroxidase (HRP) and growth and differentiation factor-5 (GDF-5). The particle size, morphology, protein encapsulation efficiency and in vitro release kinetics were assessed using SEM, FTIR, UV–visible spectroscopy and Bradford protein assays. Excellent encapsulation efficiency (93%–94%) and sustained release behaviour of BSA (∼22% protein release after 14 d) and GDF-5 proteins (∼29% protein release after 30 d) were exhibited by the optimal grades of SGnP constructs with an average particle size of 266 nm and 93 nm, respectively. Furthermore, FTIR, differential scanning calorimeter (DSC), polyacrylamide gel electrophoresis (PAGE) and NATIVE-PAGE studies results confirm successful encapsulation, stability and preserving the structural integrity of proteins placed into the core of the SGnP constructs. Evidently, a very high (93%) residual HRP enzyme activity signifies the capability of our SGnP system to protect the encapsulated proteins from process-related stresses. In vitro cytotoxicity and fluorescence cell morphology analyses using human adipose-derived mesenchymal stem cells affirmed good cytocompatibility of protein encapsulated SGnP. Overall, the study findings indicate SGnP nanocarrier-mediated protein delivery systems as a promising approach complementary to conventional techniques in tissue engineering and therapeutic applications.
Quantization, training, parasitic resistance correction, and programming techniques of memristor-crossbar neural networks for edge intelligence
Authors: Nguyen Tien Van , An Jiyong , Oh Seokjin , Truong Son Ngoc , Min Kyeong-Sik
Published: June 2022

In the internet-of-things era, edge intelligence is critical for overcoming the communication and computing energy crisis, which is unavoidable if cloud computing is used exclusively. Memristor crossbars with in-memory computing may be suitable for realizing edge intelligence hardware. They can perform both memory and computing functions, allowing for the development of low-power computing architectures that go beyond the von Neumann computer. For implementing edge-intelligence hardware with memristor crossbars, in this paper, we review various techniques such as quantization, training, parasitic resistance correction, and low-power crossbar programming, and so on. In particular, memristor crossbars can be considered to realize quantized neural networks with binary and ternary synapses. For preventing memristor defects from degrading edge intelligence performance, chip-in-the-loop training can be useful when training memristor crossbars. Another undesirable effect in memristor crossbars is parasitic resistances such as source, line, and neuron resistance, which worsens as crossbar size increases. Various circuit and software techniques can compensate for parasitic resistances like source, line, and neuron resistance. Finally, we discuss an energy-efficient programming method for updating synaptic weights in memristor crossbars, which is needed for learning the edge devices.
dipm: an R package implementing the Depth Importance in Precision Medicine (DIPM) tree and Forest-based method
Authors: Chen Victoria , Li Cai , Zhang Heping
Published: June 2022

The Depth Importance in Precision Medicine (DIPM) method is a classification tree designed for the identification of subgroups relevant to the precision medicine setting. In this setting, a relevant subgroup is a subgroup in which subjects perform either especially well or poorly with a particular treatment assignment. Herein, we introduce, dipm, a novel R package that implements the DIPM method using R code that calls a program in C.

Availability and implementation

dipm is available under a GPL-3 licence on CRAN https://cran.r-project.org/web/packages/dipm/index.html and at https://ysph.yale.edu/c2s2/software/dipm. It is continuously being developed at https://github.com/chenvict/dipm.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Pandemic and Social Work in Chile: Precarity, Precariousness and the Quest for Resistance in an Uncertain World
Authors: Reininger Taly , Muñoz-Arce Gianinna , Villalobos Cristóbal , Morales Torres Carla , Campillo Claudia
Published: June 2022

In Chile, the Covid-19 pandemic overlapped with a socio-political crisis that arose in response to the neoliberal model imposed during Pinochet’s dictatorship. Social workers have been key to addressing the multiple vulnerabilities the population has faced during the political uprising and pandemic. From a critical perspective that analyses precarity, precariousness and resistance as a continuum, this article examines SWs’ employment and intervention conditions during the pandemic and the resistances that have emerged in this context. Drawing upon a mixed sequential study that included an online survey (N = 872) and forty-two semi-structured (online) interviews, we identified that precarity and precariousness affecting professional interventions have persisted. However, findings indicate that (i) younger and less educated frontline SWs were most affected by worsening employment conditions; (ii) the shift towards tele-intervention has not only led to transformations in professional roles but also in the emergence of new surveillance mechanisms and (iii) new types of professional resistances emerged that have been identified as individual and spontaneous but nevertheless explicit in nature. We conclude that the pandemic and the on-going political crisis present social work with an opportunity to advocate for dignified working conditions as well as changing the historical subordinate position of the profession.
Prefrontal-amygdala emotion regulation and depression in multiple sclerosis
Authors: Meyer-Arndt Lil , Kuchling Joseph , Brasanac Jelena , Hermann Andrea , Asseyer Susanna , Bellmann-Strobl Judith , Paul Friedemann , Gold Stefan M , Weygandt Martin
Published: June 2022

Depression is among the most common comorbidities in multiple sclerosis and has severe psychosocial consequences. Alterations in neural emotion regulation in amygdala and prefrontal cortex have been recognized as key mechanism of depression but never been investigated in multiple sclerosis depression. In this cross-sectional observational study, we employed a functional MRI task investigating neural emotion regulation by contrasting regulated versus unregulated negative stimulus perception in 16 persons with multiple sclerosis and depression (47.9 ± 11.8 years; 14 female) and 26 persons with multiple sclerosis but without depression (47.3 ± 11.7 years; 14 female). We tested the impact of depression and its interaction with lesions in amygdala-prefrontal fibre tracts on brain activity reflecting emotion regulation. A potential impact of sex, age, information processing speed, disease duration, overall lesion load, grey matter fraction, and treatment was taken into account in these analyses. Patients with depression were less able (i) to downregulate negative emotions than those without (t = −2.25, P = 0.012, β = −0.33) on a behavioural level according to self-report data and (ii) to downregulate activity in a left amygdala coordinate (t = 3.03, PFamily-wise error [FWE]-corrected = 0.017, β = 0.39). Moreover, (iii) an interdependent effect of depression and lesions in amygdala-prefrontal tracts on activity was found in two left amygdala coordinates (t = 3.53, pFWE = 0.007, β = 0.48; t = 3.21, pFWE = 0.0158, β = 0.49) and one right amygdala coordinate (t = 3.41, pFWE = 0.009, β = 0.51). Compatible with key elements of the cognitive depression theory formulated for idiopathic depression, our study demonstrates that depression in multiple sclerosis is characterized by impaired neurobehavioural emotion regulation. Complementing these findings, it shows that the relation between neural emotion regulation and depression is affected by lesion load, a key pathological feature of multiple sclerosis, located in amygdala-prefrontal tracts.
Uncovering individual differences in fine-scale dynamics of functional connectivity
Authors: Cutts Sarah A , Faskowitz Joshua , Betzel Richard F , Sporns Olaf
Published: June 2022

Functional connectivity (FC) profiles contain subject-specific features that are conserved across time and have potential to capture brain–behavior relationships. Most prior work has focused on spatial features (nodes and systems) of these FC fingerprints, computed over entire imaging sessions. We propose a method for temporally filtering FC, which allows selecting specific moments in time while also maintaining the spatial pattern of node-based activity. To this end, we leverage a recently proposed decomposition of FC into edge time series (eTS). We systematically analyze functional magnetic resonance imaging frames to define features that enhance identifiability across multiple fingerprinting metrics, similarity metrics, and data sets. Results show that these metrics characteristically vary with eTS cofluctuation amplitude, similarity of frames within a run, transition velocity, and expression of functional systems. We further show that data-driven optimization of features that maximize fingerprinting metrics isolates multiple spatial patterns of system expression at specific moments in time. Selecting just 10% of the data can yield stronger fingerprints than are obtained from the full data set. Our findings support the idea that FC fingerprints are differentially expressed across time and suggest that multiple distinct fingerprints can be identified when spatial and temporal characteristics are considered simultaneously.
MicroRNA-9-3p: a novel predictor of neurological outcome after cardiac arrest
Authors: Beske Rasmus Paulin , Bache Søren , Abild Stengaard Meyer Martin , Kjærgaard Jesper , Bro-Jeppesen John , Obling Laust , Olsen Markus Harboe , Rossing Maria , Nielsen Finn Cilius , Møller Kirsten , Nielsen Niklas , Hassager Christian
Published: June 2022

Aims

Resuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose after hospital arrival are at high risk of mortality due to anoxic brain injury. MicroRNA are small–non-coding RNA molecules ultimately involved in gene-silencing. They show promise as biomarkers, as they are stable in body fluids. The microRNA 9-3p (miR-9-3p) is associated with neurological injury in trauma and subarachnoid haemorrhage.

Methods and results

This post hoc analysis considered all 171 comatose OHCA patients from a single centre in the target temperature management (TTM) trial. Patients were randomized to TTM at either 33°C or 36°C for 24 h. MicroRNA-9-3p (miR-9-3p) was measured in plasma sampled at admission and at 28, 48, and 72 h. There were no significant differences in age, gender, and pre-hospital data, including lactate level at admission, between miR-9-3p level quartiles. miR-9-3p levels changed markedly following OHCA with a peak at 48 h. Median miR-9-3p levels between TTM 33°C vs. 36°C were not different at any of the four time points. Elevated miR-9-3p levels at 48 h were strongly associated with an unfavourable neurological outcome [OR: 2.21, 95% confidence interval (CI): 1.64–3.15, P < 0.0001). MiR-9-3p was inferior to neuron-specific enolase in predicting functional neurological outcome [area under the curve: 0.79 (95% CI: 0.71–0.87) vs. 0.91 (95% CI: 0.85–0.97)].

Conclusion

MiR-9-3p is strongly associated with neurological outcome following OHCA, and the levels of miR-9-3p are peaking 48 hours following cardiac arrest.
Haplotype-resolved powdery mildew resistance loci reveal the impact of heterozygous structural variation on NLR genes inMuscadinia rotundifolia
Authors: Massonnet Mélanie , Vondras Amanda M , Cochetel Noé , Riaz Summaira , Pap Dániel , Minio Andrea , Figueroa-Balderas Rosa , Walker Michael Andrew , Cantu Dario
Published: June 2022

Muscadinia rotundifolia cv. Trayshed is a valuable source of resistance to grape powdery mildew. It carries 2 powdery mildew resistance-associated genetic loci, Run1.2 on chromosome 12 and Run2.2 on chromosome 18. The purpose of this study was to identify candidate resistance genes associated with each haplotype of the 2 loci. Both haplotypes of each resistance-associated locus were identified, phased, and reconstructed. Haplotype phasing allowed the identification of several structural variation events between haplotypes of both loci. Combined with a manual refinement of the gene models, we found that the heterozygous structural variants affected the gene content, with some resulting in duplicated or hemizygous nucleotide-binding leucine-rich repeat genes. Heterozygous structural variations were also found to impact the domain composition of some nucleotide-binding leucine-rich repeat proteins. By comparing the nucleotide-binding leucine-rich repeat proteins at Run1.2 and Run2.2 loci, we discovered that the 2 loci include different numbers and classes of nucleotide-binding leucine-rich repeat genes. To identify powdery mildew resistance-associated genes, we performed a gene expression profiling of the nucleotide-binding leucine-rich repeat genes at Run1.2b and Run2.2 loci with or without powdery mildew present. Several nucleotide-binding leucine-rich repeat genes were constitutively expressed, suggesting a role in powdery mildew resistance. These first complete, haplotype-resolved resistance-associated loci and the candidate nucleotide-binding leucine-rich repeat genes identified by this study are new resources that can aid the development of powdery mildew-resistant grape cultivars.
Impact of drug consumption rooms on non-fatal overdoses, abscesses and emergency department visits in people who inject drugs in France: results from the COSINUS cohort
Authors: Roux P , Jauffret-Roustide M , Donadille C , Briand Madrid L , Denis C , Célérier I , Chauvin C , Hamelin N , Maradan G , Carrieri M P , Protopopescu C , Lalanne L , Auriacombe M ,   the COSINUS Study Group, Auriacombe Marc , Berenger Cyril , Bertoia Gilles , Madrid Laélia Briand , Carrieri Maria Patrizia , Célérier Isabelle , Chauvin Carole , Chevalier Manon , Danion Jean-Marie , de Dinechin Sébastien , Denis Cécile , Grelli Natascia , Gutowski Marie , Hamelin Naomi , Jauffret-Roustide Marie , Kervran Charlotte , Kirchherr Sébastien , Lalanne Laurence , Breton Mireille Le , Maradan Gwenaëlle , Moriceau Sarah , Roux Perrine , Vilotitch Antoine
Published: June 2022

Background

The effectiveness of drug consumption rooms (DCRs) for people who inject drugs (PWID) has been demonstrated for HIV and hepatitis C virus risk practices, and access to care for substance use disorders. However, data on other health-related complications are scarce. Using data from the French COSINUS cohort, we investigated the impact of DCR exposure on non-fatal overdoses, abscesses and emergency department (ED) visits, all in the previous 6 months.

Methods

COSINUS is a 12-month prospective cohort study of 665 PWID in France studying DCR effectiveness on health. We collected data from face-to-face interviews at enrolment, and at 6 and 12 months of follow-up. After adjusting for other correlates (P-value < 0.05), the impact of DCR exposure on each outcome was assessed using a two-step Heckman mixed-effects probit model, allowing us to adjust for potential non-randomization bias due to differences between DCR-exposed and DCR-unexposed participants, while taking into account the correlation between repeated measures.

Results

At enrolment, 21%, 6% and 38% of the 665 participants reported overdoses, abscesses and ED visits, respectively. Multivariable models found that DCR-exposed participants were less likely to report overdoses [adjusted coefficient (95% CI): −0.47 (−0.88; −0.07), P = 0.023], abscesses [−0.74 (−1.11; −0.37), P < 0.001] and ED visits [−0.74 (−1.27; −0.20), P = 0.007].

Conclusion

This is the first study to show the positive impact of DCR exposure on abscesses and ED visits, and confirms DCR effectiveness in reducing overdoses, when adjusting for potential non-randomization bias. Our findings strengthen the argument to expand DCR implementation to improve PWID injection environment and health.
The Phytotoxin Thaxtomin A Is the Primary Virulence Determinant for Scab Disease of Beet, Carrot, and Radish Caused by Streptomyces scabiei
Authors: Clarke Christopher R. , Kramer Charles G. , Kotha Raghavendhar R. , Luthria Devanand L.
Published: June 2022

Several species of Streptomyces cause common scab, a major disease of potato, primarily through the phytotoxic effects of the phytotoxin thaxtomin A. Several phytopathogenic Streptomyces species have also been implicated as the causative agents of scab diseases of taproot crops including beet, carrot, radish, parsnip, and turnip. But the molecular mechanisms employed by Streptomyces to infect these crops is unknown. In this work, we tested the hypothesis that thaxtomin A biosynthesis is also necessary for Streptomyces-caused scab of beet, carrot, radish, and turnip. Thaxtomin A induced plant stunting and cell death of all four of these species. Streptomyces mutants in which the transcriptional regulator of thaxtomin A biosynthesis is disrupted were nonvirulent on all four crops, and complementation of the transcriptional regulator rescued thaxtomin A biosynthesis and plant pathogenicity to wild-type levels. These results demonstrate that thaxtomin A is the primary virulence determinant of scab disease of these other crops.
Genome Characterization and Pathogenicity of Two New Hyptis pectinata Viruses Transmitted by Distinct Insect Vectors
Authors: Reyes-Proaño Edison , Alvarez-Quinto Robert , Delgado-Jiménez José A. , Cornejo-Franco Juan F. , Mollov Dimitre , Bejerman Nicolás , Quito-Avila Diego F.
Published: June 2022

Two newly described viruses belonging to distinct families, Rhabdoviridae and Geminiviridae, were discovered co-infecting Hyptis pectinata from a tropical dry forest of Ecuador. The negative-sense RNA genome of the rhabdovirus, tentatively named Hyptis latent virus (HpLV), comprises 13,765 nucleotides with seven open reading frames separated by the conserved intergenic region 3′-AAUUAUUUUGAU-5′. Sequence analyses showed identities as high as 56% for the polymerase and 38% for the nucleocapsid to members of the genus Cytorhabdovirus. Efficient transmission of HpLV was mediated by the pea aphid ( Acyrthosiphon pisum) in a persistent replicative manner. The single-stranded DNA genome of the virus tentatively named Hyptis golden mosaic virus (HpGMV) shared homology with members of the genus Begomovirus with bipartite genomes. The DNA-A component consists of 2,716 nucleotides (nt), whereas the DNA-B component contains 2,666 nt. Pairwise alignments using the complete genomic sequence of DNA-A of HpGMV and closest relatives showed identities below the cutoff (<91% shared nt) established by the ICTV as species demarcation, indicating that HpGMV should be classified in a distinct begomovirus species. Transmission experiments confirmed that the whitefly Bemisia tabaci Middle East-Asia Minor 1 (MEAM1) is a vector of HpGMV.
An Oomycete-Specific Leucine-Rich Repeat-Containing Protein Is Involved in Zoospore Flagellum Development in Phytophthora sojae
Authors: Zhang Baiyu , Zhang Zhichao , Yong Saijiang , Yu Shuyang , Feng Hui , Yin Maozhu , Ye Wenwu , Wang Yuanchao , Qiu Min
Published: June 2022

A leucine-rich repeat (LRR) is a widespread structural motif of 20 to 30 amino acids with characteristic repetitive sequences rich in leucine. LRR-containing proteins are critical for ligand recognition and binding, participating in plant development and defense. Like plants, oomycetes also harbor genes encoding LRR-containing proteins, but their functions remain largely unknown. We identified a zoospore-upregulated gene from Phytophthora sojae with LRRs and an extra structural maintenance of chromosomes-like domain. We generated knockout and complemented knockout strains of this LRR protein and found that its deletion resulted in a pronounced reduction in zoospore mobility and chemotaxis, cyst germination, and virulence. Interestingly, micro-examination of zoospores under a scanning electron microscope revealed irregularly shaped zoospores without flagella in these deletion mutants. In addition, the reintroduction of this LRR protein into the knockout mutant reversed all the deficiencies. Our data demonstrate a critical role for the Phytophthora LRR protein in modulating zoospore development, which impairs migration to the host soybean and affects the spread of Phytophthora pathogens.
Activation and execution of the hepatic integrated stress response by dietary essential amino acid deprivation is amino acid specific
Authors: Jonsson William O. , Mirek Emily T. , Wek Ronald C. , Anthony Tracy G.
Published: June 2022

Dietary removal of an essential amino acid (EAA) triggers the integrated stress response (ISR) in liver. Herein, we explored the mechanisms that activate the ISR and execute changes in transcription and translation according to the missing EAA. Wild‐type mice and mice lacking general control nonderepressible 2 (Gcn2) were fed an amino acid complete diet or a diet devoid of either leucine or sulfur amino acids (methionine and cysteine). Serum and liver leucine concentrations were significantly reduced within the first 6 h of feeding a diet lacking leucine, corresponding with modest, GCN2‐dependent increases in Atf4 mRNA translation and induction of selected ISR target genes (Fgf21, Slc7a5, Slc7a11). In contrast, dietary removal of the sulfur amino acids lowered serum methionine, but not intracellular methionine, and yet hepatic mRNA abundance of Atf4, Fgf21, Slc7a5, Slc7a11 substantially increased regardless of GCN2 status. Liver tRNA charging levels did not correlate with intracellular EAA concentrations or GCN2 status and remained similar to mice fed a complete diet. Furthermore, loss of Gcn2 increased the occurrence of ribosome collisions in liver and derepressed mechanistic target of rapamycin complex 1 signal transduction, but these changes did not influence execution of the ISR. We conclude that ISR activation is directed by intracellular EAA concentrations, but ISR execution is not. Furthermore, a diet devoid of sulfur amino acids does not require GCN2 for the ISR to execute changes to the transcriptome.
Investigation of the Sectorized Corneal Thickness of Eyes With Corneal Endothelial Dysfunction Using Anterior-Segment Optical Coherence Tomography
Authors: Omoto Takashi , Kim Minjae , Goto Hiroki , Abe Yuito , Ono Takashi , Taketani Yukako , Toyono Tetsuya , Yoshida Junko , Usui Tomohiko , Yamagami Satoru , Aihara Makoto , Miyai Takashi
Published: June 2022

Purpose:

The aim of this study was to investigate the sectorized corneal thickness of eyes with corneal endothelial dysfunction using anterior-segment optical coherence tomography.

Methods:

We retrospectively collected anterior-segment optical coherence tomography data conducted before endothelial keratoplasty on 53 eyes of 53 patients with corneal endothelial dysfunctions including Fuchs endothelial corneal dystrophy, bullous keratopathy (BK) after trabeculectomy, and BK after laser iridotomy and from 18 normal eyes of 18 subjects. The imaging points were divided into 17 sectors. The mean for each sector was calculated and compared with the corresponding superior/inferior and temporal/nasal sectors.

Results:

In the normal eyes, the superior sectors were thicker than the inferior and the temporal sectors thinner than the nasal. In the diseased eyes, the superior sectors were thicker than the inferior in all subgroups; however, this tendency was no longer observed after the values were divided by the mean for the normal eyes. No significant differences were found on horizontal comparisons; however, after the values were divided by the mean for the normal eyes, the temporal sectors were thicker than the nasal. When comparing the values between the with-hole and the without-hole sides in the BK after laser iridotomy eyes, the sectors on the with-hole side were thicker than the other side.

Conclusions:

Corneal thickness of endothelial dysfunction was thicker in the superior sectors than the inferior but at a similar level to normal eyes. No significant differences were found for horizontal comparisons but, based on comparison with the normal eyes, the temporal sectors were thicker than the nasal.
Structural and Metabolic Imaging after Short-term Use of the Balance Goggles System in Glaucoma Patients: A Pilot Study
Authors: Sun Michelle T. , Beykin Gala , Lee Wen-shin , Sun Yang , Chang Robert , Nunez Mariana , Li Katherine Zhongqiu , Knasel Cara , Rich Collin , Goldberg Jeffrey L.
Published: June 2022

Precis:

Short-term use of the Balance Goggles System in glaucoma patients was not associated with observable changes in conventional OCT imaging but metabolic imaging using peripapillary flavoprotein fluorescence may represent a useful adjuctive investigation.

Objective:

To determine whether the intraocular pressure (IOP)-lowering effects of the Balance Goggles System (BGS) are accompanied by changes in retinal thickness measured by ocular coherence tomography, retinal vascular density measured by OCT-angiography, or novel peripapillary metabolic profiling using flavoprotein fluorescence (FPF) measured by a fundus camera.

Design:

Prospective comparative case-series.

Subjects:

8 eyes from 8 patients with open-angle glaucoma ranging from mild to severe.

Methods:

In this prospective, single-center, open-label, non-randomized, single-arm study patients received a baseline evaluation including retinal imaging, then one hour of negative pressure application through the BGS, followed by repeat retinal imaging. Participants then used the BGS at home for 1 month and underwent a repeat evaluation at the conclusion of the trial.

Main Outcome Measures:

Changes in nerve fiber layer thickness, OCTA vascular parameters and FPF scores.

Results:

Mean baseline IOP was 18.0±3.1 mmHg and there was no significant change in IOP at follow-up. At 1 month compared to baseline, there was a statistically significant improvement in FPF optic nerve head rim scores (12.7±11.6 to 10.5±7.5; P=0.04). Additionally, there was there was a trend towards an increase in RNFL thickness after 1 month (69.5±14.2 to 72.0±13.7; P=0.1), but there were no statistically significant differences observable with any of the OCTA vascular parameters either at 1 hour or after 1 month.

Conclusions:

There were no significant changes observable using conventional OCT imaging following short-term use of the BGS, although metabolic imaging using FPF may be a useful potential biomarker to complement existing investigations. Additional studies are warranted to further investigate these changes.
The feasibility and safety of stepwise protocol in cardiopulmonary exercise testing-exercise stress echocardiography for subjects with heart failure
Authors: Huang Wei-Ming , Chen Chiao-Nan , Chen Yung-Hsin , Yen Ju-Hsin , Tseng Tzu-Ying , Cheng Hao-Min , Yu Wen-Chung , Chen Chen-Huan , Sung Shih-Hsien
Published: June 2022

Background:

Exercise stress testing using a ramp protocol has been favored for cardiopulmonary exercise testing (CPX) in patients with heart failure (HF). However, the stepwise protocol for CPX was preferred for its possible combination with exercise stress echocardiography (ESE). We, therefore, investigated the feasibility and safety of using a stepwise protocol for CPX-ESE in patients with HF.

Methods:

Ambulatory outpatients with chronic HF were enrolled for a symptom-limited stepwise bicycle exercise test in the semi-supine position on a cycle ergometer. The test was started at a workload of 30 W and increased by 15 W every 3 minutes until maximal exertion. The echocardiographic and respiratory variables and any complications during the exercise were recorded.

Results:

Among a total of 36 participants (age 61.2 ± 12.4 years; 69.4% men), all subjects achieved anerobic threshold during CPX-ESE and reached 72.3% of the age-predicted peak heart rate. The peak oxygen consumption was 14.7 mL/kg/min, and the peak RER was 1.25. There were no severe adverse complications, and only two minor rhythmic events were reported: nonsustained supraventricular tachycardia and isolated ventricular premature beats. The echocardiographic images acquired at each stage were of good quality in 92.6% of all acquisitions, and the intra-observer and interobserver repeatability was >80%.

Conclusion:

The stepwise protocol, with an initial workload of 30 W, followed by 15 W increments every 3 minutes, was feasible and provided an adequate stress load for patients with HF. This exercise stress modality was safe and well-tolerated.
Endoscopic small bowel balloon dilations in patients with Crohn’s disease: a Danish nationwide cohort study, 1997–2015
Authors: Wewer Mads Damsgaard , Karstensen John Gásdal , Burisch Johan
Published: June 2022

Objective

Small bowel strictures are a common complication in Crohn’s disease. Endoscopic balloon dilation (EBD) is an emerging therapeutic approach that is minimally invasive and helps to preserve the bowel. The aim of this study was to describe the use of EBD in adult Crohn’s disease patients with small bowel strictures.

Methods

This nationwide cohort comprised individuals ≥18 years old, diagnosed with Crohn’s disease in Denmark between 1 January 1997 and 31 December 2015, according to the National Patient Registry (NPR).

Results

The cohort consisted of 9737 incident Crohn’s disease patients that were followed for a median of 8.2 years [interquartile range (IQR) = 4.1–13.3]. During the observation period, a total of 90 (1%) patients underwent a small bowel-related EBD. After a follow-up period of a median of 3.4 (IQR = 1.8–5.0) years, primary small bowel strictures treated only with one dilation and no subsequent small bowel surgery accounted for 29 (59%) of 49 cases. A median of 7.2 (IQR = 2.4–13.2) months after their first dilation, 13 (27%) of those 49 patients underwent small bowel surgery. Forty-one patients with postsurgical strictures were dilated after a median of 6.5 (IQR = 2.5–10.2) years following small bowel surgery. Postsurgical strictures treated with only one dilation and no further small bowel surgery accounted for 20 (49%) of the 41 cases.

Conclusion

The frequency of EBD in this Danish nationwide cohort was low. During a median follow-up of 5 years after EBD, most patients did not require further surgery. This suggests that EBD is an effective treatment and could be offered to more patients with Crohn’s disease.
Coefficient of Fat Absorption to Measure the Efficacy of Pancreatic Enzyme Replacement Therapy in People With Cystic Fibrosis
Authors: Borowitz Drucy , Aronoff Nell , Cummings Linda C. , Maqbool Asim , Mulberg Andrew E.
Published: June 2022

Objectives

We sought data on the validity, reliability, responsiveness, and feasibility of the coefficient of fat absorption (CFA) as a measure of pancreatic enzyme replacement therapy (PERT) efficacy in people with cystic fibrosis (pwCF) and reviewed the literature for alternative measures.

Methods

We searched PubMed for the Medical Subject Heading cystic fibrosis and the key words cystic fibrosis, fat absorption, CFA, and fecal fat imbalance; historical articles; and citations in bibliographies.

Results

The lower the CFA, the greater its variability; thus, it is less variable in healthy individuals who have higher CFA than pwCF. In addition, the test-retest values for CFA are more variable in pwCF than the general population. There is no correlation between CFA and body mass index or PERT dose but CFA is related to gastrointestinal signs and symptoms. Research-quality CFA studies are expensive, time consuming, and odious to pwCF and research staff. Sparse stool tests, breath tests, and blood tests of fat absorption have been studied as potential alternatives to CFA to measure PERT efficacy.

Conclusions

Based on the evidence, we conclude that CFA as a measure of the efficacy of PERT is more of a “coal standard” than a gold standard; developing suitable alternatives should be a priority.
The Additional Diagnostic Benefit of Pancreatic Cancer Molecular Profiling After Germline Testing
Authors: Walker Evan J. , Blanco Amie M. , Carnevale Julia , Cinar Pelin , Collisson Eric A. , Tempero Margaret A. , Ko Andrew H.
Published: June 2022

Objectives

Germline genetic testing is universally recommended for patients with pancreatic cancer to guide therapeutic selection, but tumor molecular profiling (TMP) is not. We aimed to determine the real-world additional diagnostic benefit of TMP after germline testing for detecting therapeutically actionable alterations.

Methods

Medical records and genetic test reports were reviewed for all patients who underwent germline testing and TMP at the University of California San Francisco during January 2016–January 2020. The detection rate of actionable alterations with germline testing alone was compared to that with both germline testing and TMP.

Results

Among 738 eligible patients, 144 (20%) met study criteria. Germline testing detected 10 actionable alterations in 10 patients. Tumor molecular profiling identified 3 new therapeutic targets among these 10 patients and 45 targets in 41 additional patients, increasing the number of patients with actionable findings from 10 (7%) to 51 (35%). Most actionable alterations (35/58, 60%) involved genes associated with the Homologous Recombination DNA Damage Repair pathway.

Conclusions

Tumor molecular profiling after germline testing increased the detection of actionable alterations by 5-fold. Tumor molecular profiling is a necessary complement to germline genetic testing to fully inform therapeutic decision making for all patients with pancreatic cancer.
Combination of Body Mass Index and Fasting Blood Glucose Improved Predictive Value of New-Onset Prediabetes or Diabetes After Acute Pancreatitis
Authors: Guo Shao-Yan , Yang Hai-Yun , Ning Xiao-Yan , Guo Wan-Wei , Chen Xiao-Wu , Xiong Man
Published: June 2022

Objectives

We sought to evaluate whether combining body mass index (BMI) and fasting blood glucose (FBG) can refine the predictive value of new-onset prediabetes/diabetes after acute pancreatitis (NODAP).

Methods

In this retrospective cohort study, we used Kaplan–Meier analysis to compare differences in the NODAP rate among 492 patients with different BMI or FBG levels, or with the combination of these 2 factors mentioned above.

Results

In all, 153 of 492 (31.1%) eligible patients finally developed NODAP. According to univariate and multivariate analyses, BMI (hazard ratio, 2.075; 95% confidence interval, 1.408–3.060; P < 0.001) and FBG (hazard ratio, 2.544; 95% confidence interval, 1.748–3.710; P < 0.001) were important predictors of the incidence of NODAP. Subsequently, we divided 492 eligible patients into 3 groups according to the median BMI and FBG values, and found that the NODAP rate in the high-risk group was significantly higher than that in the medium-risk group (P = 0.018) or the low-risk group (P < 0.001).

Conclusions

Body mass index and FBG are independent predictors of NODAP. The combination of BMI and FBG can refine the prediction of NODAP and identify candidates for clinical prevention.
The Characteristics and Risk Factors of Asparaginase-Associated Pancreatitis in Pediatric Acute Lymphoblastic Leukemia
Authors: Kuo Shu-Han , Chen Jiann-Shiuh , Cheng Chao-Neng , Lo Hsiao-Yu , Chen Wei-Che , Lai Fu-Ping , Yang Yao-Jong
Published: June 2022

Objective

This study aimed to elucidate the characteristics and the risk factors for asparaginase-associated pancreatitis (AAP) in pediatric acute lymphoblastic leukemia (ALL) under the Taiwan Pediatric Oncology Group (TPOG)–ALL regimen.

Methods

The study was conducted by reviewing the chart records of 191 patients aged 1 to 18 years treated with TPOG-ALL (2002 and 2013) protocols at the National Cheng Kung University Hospital, Tainan, Taiwan, from 2002 to 2019. The disease incidence, clinical presentations, laboratory data, complications, and outcomes of AAP were investigated.

Results

The incidence of AAP was 4.7%. The incidence was significantly higher in children treated with the TPOG-ALL-2013 (n = 62) than TPOG-ALL-2002 (n = 129) protocol (11.3% vs 1.6%, P = 0.006). Multivariate analysis identified using TPOG-ALL-2013 protocol was an independent risk factor for AAP. Pancreatic necrosis or pseudocysts developed in 7 patients (78%). Notably, 1 AAP case (11%) developed diabetes mellitus and 4 (44%) had chronic pancreatitis during a 1-year observational period. None were mortality.

Conclusions

The incidence of AAP was 4.7% in ALL patients treated with TPOG-ALL protocol. Although a higher cumulative dose of asparaginase in TPOG-ALL-2013 may attribute to the pancreatic toxicity, unidentified factors such as genetic predisposition or other drugs still need further study.
Unexpected Benefits in Single Institution Experience With Successful Implementation of a Standardized Perioperative Protocol in Pediatric Thyroidectomy
Authors: Cossen Kristina , Santore Matthew T. , Prickett Kara K. , Goudy Steven L. , Heiss Kurt F. , Shanker Kanika , Alazraki Adina L. , Patterson Briana C.
Published: June 2022

Introduction:

To illustrate how quality improvement can produce unexpected positive outcomes.

Methods:

We compared a retrospective review of perioperative management and outcomes of baseline 122 pediatric total thyroidectomies to 121 subsequent total thyroidectomies managed by an Electronic Medical Record protocol in a large, free-standing children’s healthcare system. Process measures included serum calcium measurement 6−12 hours postoperatively; parathyroid hormone measurement 6 hours postoperatively; preoperative iodine for Graves disease, and postoperative prophylactic calcium carbonate administration. In addition, we completed 4 Plan-Do-Study-Act (PDSA) cycles, focusing on implementation, refinement, usage, education, and postoperative calcitriol administration. The primary outcome included transient hypocalcemia during admission.

Results:

All perioperative process measures improved over PDSA cycles. Measurement of postoperative serum calcium increased from 42% at baseline to 100%. Measurement of postoperative PTH increased from 11% to 97%. Preoperative iodine administration for Graves disease surgeries improved from 72% to 94%. Postoperative calcium carbonate administration increased from 36% to 100%. There was a trend toward lower rates of severe hypocalcemia during admission over the subsequent PDSA cycles starting at 11.6% and improving to 3.4%. With the regular review of outcomes, surgical volume consolidated among high-volume providers, associated with a decrease in a permanent hypoparathyroid rate of 20.5% at baseline to 10% by the end of monitoring.

Conclusions:

In standardizing care at 1 large pediatric institution, implementing a focused quality improvement project involving the perioperative management of transient hypocalcemia in total thyroidectomy pediatric patients resulted in additional, unanticipated improvements in patient care.
Pulmonary Artery Angiomatoid Fibrous Histiocytoma Mimicking a Large Pulmonary Embolism
Authors: Haug Logan P. , Zarka Matthew A. , D’Cunha Jonathan , Downey Francis X. , Seetharam Mahesh , Yang Ming
Published: June 2022

A 39-year-old man presented with progressive dyspnea and lower extremity edema. Doppler ultrasound demonstrated bilateral leg partially occluded venous thromboses. A V/Q scan revealed a mismatched perfusion defect involving the entire right middle and lower lobes. Subsequent CT pulmonary angiogram revealed a mass lesion occluding the right interlobar pulmonary artery. Endobronchial ultrasound–guided fine-needle aspiration of the mass was concerning for neoplasm. 18F-FDG PET/CT demonstrated marked hypermetabolism of the mass lesion. Patient underwent transmediastinal right pneumonectomy with histopathologic diagnosis of pulmonary artery angiomatoid fibrous histiocytoma, a rare etiology mimicking large pulmonary artery embolism.
Palmar Creases and Their Implication on Carpal Tunnel Surgery
Authors: Mujadzic Tarik , Friedman Harold I. , Atwez Abdelaziz , Botonjic Hata , Mujadzic Mirza M. , Chen Elliott , Gilstrap Jarom N. , Mujadzic Mirsad M.
Published: June 2022

Background

A thorough knowledge of normal and variant anatomy of the wrist and hand is fundamental to avoiding complications during carpal tunnel release. The purpose of this study was to document variations of the surface anatomy of the hand to identify a safe zone in which the initial carpal tunnel incision could be placed. The safe zone was identified as the distance between the radial side of hook of hamate and the ulnar edge of the origin of the motor branch of the median nerve (MBMN).

Methods

Kaplan's cardinal line and other superficial markers were used to estimate the size of the safe zone, in accordance to prior published anatomical studies. The presence of a longitudinal palmar crease (thenar, median, or ulnar creases) within the safe zone was recorded.

Results

Of the 150 participants (75 male, 75 female) examined, the average safe zone widths were 10.85 (right) and 10.28 (left) mm. In all the hands examined, 86.33% of the safe zones (259 of 300) contained a longitudinal palmar crease. In the White population (n = 50), the average safe zone widths were 11.49 (right) and 10.01 (left) mm; in the African American population (n = 50), the average safe zone widths were 12.27 (right) and 12.01 (left) mm; and in the Asian population (n = 50), the average safe zone widths were 8.79 (right) and 8.82 (left) mm. On overage, males had a larger safe zone width than females by 4.55 mm.

Conclusions

Although there seems to be variability between race and sex with regard to safe zone width, finding 86.33% of longitudinal palmar creases within the safe zone suggests that, for most patients, the initial carpal tunnel surgery incision may be hidden within the palmar crease while minimizing the risk of motor branch of the median nerve injury. Overall, the safe zone width is on average up to 10.5 mm measured from the hook of the hamate along Kaplan's cardinal line.
The Effect of Fat Grafting on Expansion Pressures in Expander-Based Postmastectomy Breast Reconstruction
Authors: Browne Donald T. , Monserrat Javier , Matas Aina , Sese Borja , Llull Ramon
Published: June 2022

Introduction

The impact of fat grafting on the viscoelasticity of irradiated tissues is poorly defined. We investigate the effect of subcutaneous fat grafting on postmastectomy tissue expansion in patients undergoing delayed breast reconstruction. We quantify observed viscoelastic and trophic changes of the skin envelope. We hypothesize that fat grafting changes the trophic and viscoelastic properties of the breast soft tissue envelope.

Methods

Postmastectomy defects delayed more than 2 years and reconstructed with subpectoral tissue expanders were prospectively studied. Control (no irradiation, no fat grafting, n = 7), fat grafted (no irradiation, fat grafting n = 8), and irradiated plus fat grafting (irradiation, fat grafting, n = 9) groups were included. Hydrostatic pressures of the tissue expanders were measured before and immediately after expansion, and again postexpansion day 1. Pressure changes calculated as “postexpansion-relaxation interval”: difference between maximal pressure at each expansion and the minimal pressure before the next expansion session. Differences were analyzed between groups.

Results

Hydrostatic pressure plots reflect the soft tissue ability to accommodate sequential expansion. Fat grafted breasts demonstrated a statistically significant increased postexpansion-relaxation interval versus the nongrafted control group (P < 0.0001). Irradiated plus fat grafting breasts achieve similar postexpansion relaxation interval to the control group (P = 0.597). These changes are observed at postoperative week 6. Viscoelastic changes impact the overall expansion time: the fat grafted group achieved total expansion 2 weeks earlier than the nongrafted control group (P = 0.019). The fat grafted, radiated group completed expansion in similar time interval as nongrafted control group.

Conclusions

Observed viscoelastic changes impact the overall expansion time. Fat grafting in nonradiated mastectomy defects allows for shorter expansion period. Fat grating in radiated postmastectomy defects allows expansion durations equivalent to nonradiated, nonfat grafted control defects. There is a delayed effect of fat grafting observed at postoperative week 6.
A Comparison of Complication Rates in Wise Pattern Versus Vertical Breast Reduction
Authors: Rodgers Ariel , Berry Hunter , O'Brien Robert , Davis Jared M.
Published: June 2022

Background

Breast reduction has a well-chronicled history and remains a common reason for patients to seek plastic surgery consultation. The Wise pattern is the most common skin reduction pattern in the United States. Vertical pattern reduction is also widely used and offers the potential for decreased scar burden. Both patterns have been used with a variety of pedicles for preservation of the nipple areolar complex, which may also impact complication rate and patient satisfaction. There is a preponderance of literature on breast reduction surgery but limited comparative data on the safety profile of these patterns. The purpose of this article is to review the comparative literature, with emphasis on the overall risk of complications.

Methods

OVID and PubMed were used to query the literature for articles comparing complication rates in both Wise pattern and vertical breast reduction. Inclusion criteria were case series that encompassed both vertical and Wise pattern reductions and cited the rate of complications. Complications included in our analysis of total complication rate were as follows: hematoma, seroma, infection, dehiscence, fat necrosis, skin necrosis, and nipple areolar complex necrosis. We excluded standing cutaneous deformity as a complication. Articles that included oncoplastic breast reductions were also excluded. The primary analysis was an inverse variance-weighted random-effect meta-analysis of overall complication rate, with the association between the technique and overall complication rate quantified using odds ratios.

Results

Eight articles were identified that met inclusion criteria, representing 963 patients (525 Wise pattern and 438 vertical pattern). The overall complication rate pooled across the studies favored vertical pattern reduction, but the result was not definitive.

Conclusions

Vertical pattern breast reduction can be done safely. Our statistical analysis found a trend toward decreased complications with vertical reductions, but did not reach statistical significance. Patients seeking breast reduction are a heterogeneous population with respect to breast size, degree of ptosis, body habitus, body mass index, comorbidities, and acceptance of scars. It remains important to individualize the approach to the patient and their needs. More quantitative, comparative data, especially from randomized controlled trials, would be useful to further evaluate the relative safety profiles of the 2 patterns.