bluuebunny/crossref_metadata_2025 huggingface dataset:
DeePVP: Identification and classification of phage virion proteins using deep learning
Authors: Fang Zhencheng , Feng Tao , Zhou Hongwei , Chen Muxuan
Published: August 2022

Background

Many biological properties of phages are determined by phage virion proteins (PVPs), and the poor annotation of PVPs is a bottleneck for many areas of viral research, such as viral phylogenetic analysis, viral host identification, and antibacterial drug design. Because of the high diversity of PVP sequences, the PVP annotation of a phage genome remains a particularly challenging bioinformatic task.

Findings

Based on deep learning, we developed DeePVP. The main module of DeePVP aims to discriminate PVPs from non-PVPs within a phage genome, while the extended module of DeePVP can further classify predicted PVPs into the 10 major classes of PVPs. Compared with the present state-of-the-art tools, the main module of DeePVP performs better, with a 9.05% higher F1-score in the PVP identification task. Moreover, the overall accuracy of the extended module of DeePVP in the PVP classification task is approximately 3.72% higher than that of PhANNs. Two application cases show that the predictions of DeePVP are more reliable and can better reveal the compact PVP-enriched region than the current state-of-the-art tools. Particularly, in the Escherichia phage phiEC1 genome, a novel PVP-enriched region that is conserved in many other Escherichia phage genomes was identified, indicating that DeePVP will be a useful tool for the analysis of phage genomic structures.

Conclusions

DeePVP outperforms state-of-the-art tools. The program is optimized in both a virtual machine with graphical user interface and a docker so that the tool can be easily run by noncomputer professionals. DeePVP is freely available at https://github.com/fangzcbio/DeePVP/.
Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man
Authors: Bando Hironori , Brinkmeier Michelle L , Castinetti Frederic , Fang Qing , Lee Mi-Sun , Saveanu Alexandru , Albarel Frédérique , Dupuis Clémentine , Brue Thierry , Camper Sally A
Published: August 2022

Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/−; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.
Knockdown of circ_0002194 protects against oxidized low-density lipoprotein-induced cell damage via the regulation of the miR-637/PACS2 axis in human vascular endothelial cells
Authors: Mei Ruyang , Wu Mei , Ren Fei
Published: August 2022

OBJECTIVES

Atherosclerosis is one of the most common cardiovascular diseases. The functional roles of circular (circ) RNAs have been discovered in atherosclerosis. Our goal was to explore the regulation and mechanism of circ_0002194 in oxidized low-density lipoprotein-induced human vascular endothelial cells.

METHODS

Circ_0002194, microRNA-637 (miR-637) and phosphofurin acidic cluster sorting protein 2 (PACS2) levels were determined through the reverse transcription-quantitative polymerase chain reaction. Cell viability was detected using the Cell Counting Kit-8 assay, and angiogenetic ability was analysed via the tube formation assay. Flow cytometry was used to measure cell apoptosis. Western blot was performed to examine protein expression. Oxidative stress was assessed using commercial kits. The RNA immunoprecipitation assay and dual-luciferase reporter assay were conducted for target analysis.

RESULTS

Treatment with oxidized low-density lipoprotein induced the upregulation of circ_0002194 in endothelial cells. Cell viability and angiogenesis were promoted while cell apoptosis and oxidative stress were reduced by the downregulation of circ_0002194 in the cell model. Furthermore, miR-637 was identified as an miRNA target of circ_0002194, and the regulatory role of circ_0002194 was associated with the sponge effect on miR-637. Moreover, circ_0002194 could regulate PACS2 by affecting miR-637. Additionally, miR-637 suppressed endothelial cell damage by partly mediating the expression of PACS2.

CONCLUSIONS

The results demonstrated that circ_0002194 facilitated endothelial cell dysfunction in atherosclerosis partly through upregulating PACS2 by targeting miR-637.
Longitudinal Assessment of the Enhanced Liver Fibrosis Score in the Era of Contemporary HIV and Hepatitis C Virus Treatment
Authors: Gardner Annelys Roque , Ma Yifei , Bacchetti Peter , Price Jennifer C , Kuniholm Mark H , French Audrey L , Gange Stephen , Adimora Adaora A , Minkoff Howard , Kassaye Seble , Ofotokun Igho , Rosenberg William , Kovacs Andrea A Z , Tien Phyllis C
Published: August 2022

Background

The trajectory of liver fibrosis is not well understood in the contemporary era of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) therapy.

Methods

We assessed the Enhanced Liver Fibrosis (ELF) score, aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) in 116 women with HIV/HCV coinfection over a 4-year period. Random-effects linear regression models examined the rate of fibrosis change 1–2 years before starting HCV treatment, within 1 year before starting (peri-HCV treatment), within 1 year after and 1–2 years post-HCV treatment in unadjusted and adjusted models including age, race, and changes from pretreatment of factors that might affect fibrosis (eg, alcohol, integrase strand inhibitor [INSTI] use, waist circumference, CD4 count).

Results

INSTI use nearly doubled from pre- to peri-HCV treatment. In unadjusted analysis, there was a 3.3% rate of rise in ELF pre-HCV treatment, 2.2% and 3.6% rate of decline during the peri- and 1-year post-HCV treatment period, respectively, followed by a 0.3% rise. Similar findings were observed for APRI and FIB-4. There was little effect on the estimated fibrosis trajectories after adjustment.

Conclusions

The apparent lack of decline in biomarkers of liver fibrosis beyond 1 year after HCV cure suggests that continued monitoring of liver fibrosis and interventions to mitigate progression in people with HIV after HCV cure remains essential.
Behavior Problems, Self-Esteem, and Prosocial Behavior in Siblings of Children With Chronic Physical Health Conditions: An Updated Meta-Analysis
Authors: Pinquart Martin
Published: August 2022

Objective

Chronic physical health conditions (CPHC) of children affect the whole family. The aim of the present meta-analysis was to compare levels of internalizing, externalizing, and total problems as well as self-esteem/positive self-concept and prosocial behavior of the healthy siblings with children from families not affected by CPHC and test norms, respectively.

Methods

A systematic search for literature was conducted using the electronic data bases CINAHL, PsycInfo, PubMed, PSYNDEX, and Web of Science. In total, results from 216 studies were included in random-effects meta-analyses that had been published or made available online before February 15, 2022.

Results

Healthy siblings of children with CPHC had elevated levels of internalizing (g = .18 standard deviation units), externalizing (g = .13), and total behavior problems (g = .22), and effect sizes were found to be small to very small. While levels of self-esteem did, on average, not vary between healthy children with and without a sibling with CPHC or test norms (g = .08), higher levels of prosocial behavior were found in the healthy siblings of children with CPHC (g = .18). In addition, some moderating effects of kind of CPHC and its intrusiveness as well as mortality risk, country, sociodemographic equivalence of the compared groups, and year of publication were identified.

Conclusions

It is concluded that CPHC of a child can have negative as well as positive effects on psychosocial outcomes of healthy siblings. Psychosocial interventions are recommended for healthy siblings at elevated risk for psychological problems.
How do plant roots overcome physical barriers?
Authors: Li Daiyan , Jia Zhongtao
Published: August 2022

This article comments on:

Bello-Bello E, Rico-Chambrón TY, Ortiz Ramírez LA, Rellán Álvarez R, Herrera Estrella L. 2022. ROOT PENETRATION INDEX 3, a major quantitative trait locus associated with root system penetrability in Arabidopsis. Journal of Experimental Botany 73, 4716–4732.
Family Court Responses to Claims of Parental Alienation in Quebec
Authors: Paquin-Boudreau Amylie , Poitras Karine , Bala Nicholas
Published: August 2022

An increasing number of cases of parental separation involve high conflict and claims that a parent is alienating a child. This study analyzes reported family law cases involving claims of parental alienation in Quebec between 2017 and 2020 (n = 164). Bivariate analyzes were undertaken to establish correlations between family characteristics (child's age, safety issues concerning the children and parents, severity of the parental conflict, child's age, allegations of domestic violence and child abuse) and court decisions. Judges made a finding of parental alienation in a minority of cases where a claim of alienation was made, and in more than a quarter of cases did not resolve the claim. Issues of family violence were raised in about a quarter of the cases where alienation was an issue. The courts rarely dismissed a claim of violence and made a finding of alienation. The most common outcome of all cases was a continuation of the status quo, with a custody reversal in only a few cases (n = 7). Mothers were more often alleged to be engaging in alienating behaviour, but there is a lower rate of judicial substantiation of alienation against mothers, and the study did not find evidence of gender bias. Judicial findings of alienation were associated with substantiation by a child custody evaluator or the child protection service. Only a small portion of cases resulted in orders psychosocial interventions. The authors argue that courts, agencies professionals need to better address issues of parental alienation and family violence.
Clinically amyopathic dermatomyositis manifested after the allogeneic haematopoietic stem cell transplantation: Case presentation and literature review
Authors: Miyagi Riko , Nakachi Sawako , Tamaki Yasutaro , Doi Mototsugu , Nakajima Tomo , Kitamura Sakiko , Tomori Shohei , Hanashiro Taeko , Tamaki Keita , Morichika Kazuho , Nishi Yukiko , Morishima Satoko , Fukushima Takuya , Masuzaki Hiroaki
Published: August 2022

Clinically amyopathic dermatomyositis (CADM) lacks muscle symptoms, associated with rapidly progressive interstitial lung disease. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody has been identified as a disease-labelling autoantibody. We report two cases of CADM manifested after the allogeneic haematopoietic stem cell transplantation (allo-HSCT)—Case 1: a 56-year-old man with acute leukaemia received the allo-HSCT and Case 2: a 45-year-old female patient with lymphoma received the allo-HSCT. She received donor lymphocyte infusion because of a post-transplant relapse. After allo-HSCT or donor lymphocyte infusion, Gottron papules emerged, and both patients were diagnosed as CADM based on dermatological findings coupled with the positivity of anti-MDA-5 antibody, accompanied by interstitial shadows consistent with ILD on chest computed tomography. Case 2 was initially diagnosed as a kind of chronic graft versus host disease. Their symptoms were improved by the combination of immunosuppressive agents with a concomitant decrease in anti-MDA-5 antibody levels. For Case 2, rituximab was subsequently started for relapse of lymphoma, resulting in a substantial decrease in the level of anti-MDA-5 antibody and improvement in rash and ILD. Our cases raise a possibility that CADM emerges after the HSCT, highlighting the importance of early diagnosis to avoid fated progression into ILD.
Development of IgG4-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy: A case report
Authors: Yoshida Misaki , Mizushima Ichiro , Tsuge Shunsuke , Takahashi Yoshinori , Zoshima Takeshi , Nishioka Ryo , Hara Satoshi , Ito Kiyoaki , Kawano Mitsuhiro
Published: August 2022

This report describes a patient diagnosed with immunoglobulin G4 (IgG4)-related pancreatitis and kidney disease 7 years after the onset of undiagnosed lymphadenopathy. A 48-year-old Japanese woman presented with fatigue and leg oedema. Computed tomography showed perigastric lymphadenopathy, for which she underwent a laparoscopic biopsy of the perigastric lymph nodes. Although histopathological examination of the lymph nodes did not lead to a definitive diagnosis, serological tests revealed elevated serum IgG4 levels (558 mg/dl) and IgG4 immunostaining of the lymph nodes showed IgG4-positive plasma cell infiltration, leading to the suspicion of IgG4-related disease. Further workup revealed no organ lesion other than lymphadenopathy. At age 55 years, despite having no subjective symptoms, contrast-enhanced computed tomography showed low-density lesions in the tail of the pancreas and the left kidney. Histopathological examination showed lymphocyte infiltration, consisting of a mixture of plasma cells and eosinophils, in both organs and obliterative phlebitis in the pancreas. IgG4 immunostaining of the kidney specimens showed 160 IgG4-positive cells per high-powered field, with the IgG4+/IgG+ cell ratio being almost 100%, leading to a diagnosis of IgG4-related pancreatitis and kidney disease. Treatment with prednisolone for 2 months resulted in lesion improvement. Although the diagnosis of IgG4-related lymphadenopathy is often challenging in patients with lymphadenopathy alone, findings in the present patient emphasise the importance of long-term follow-up, as it may allow early detection of involvement of other organs by IgG4-related disease.
Transcription factor NTL9 negatively regulates Arabidopsis vascular cambium development during stem secondary growth
Authors: Sugimoto Hiroki , Tanaka Tomoko , Muramoto Nobuhiko , Kitagawa-Yogo Ritsuko , Mitsukawa Norihiro
Published: August 2022

In plant stems, secondary vascular development is established through the differentiation of cylindrical vascular cambium, producing secondary xylem (wood) and phloem (bast), which have economic importance. However, there is a dearth of knowledge on the genetic mechanism underlying this process. NAC with Transmembrane Motif 1-like transcription factor 9 (NTL9) plays a central role in abiotic and immune signaling responses. Here, we investigated the role of NTL9 in vascular cambium development in Arabidopsis (Arabidopsis thaliana) inflorescence stems by identifying and characterizing an Arabidopsis phloem circular-timing (pct) mutant. The pct mutant exhibited enhanced vascular cambium formation following secondary phloem production. In the pct mutant, although normal organization in vascular bundles was maintained, vascular cambium differentiation occurred at an early stage of stem development, which was associated with increased expression of cambium-/phloem-related genes and enhanced cambium activity. The pct mutant stem phenotype was caused by a recessive frameshift mutation that disrupts the transmembrane (TM) domain of NTL9. Our results indicate that NTL9 functions as a negative regulator of cambial activity and has a suppressive role in developmental transition to the secondary growth phase in stem vasculature, which is necessary for its precise TM domain-mediated regulation.
Sobolev regularity for linear growth functionals acting on ℂ-elliptic operators
Authors: Wozniak Piotr
Published: August 2022

In this paper, we prove the higher Sobolev regularity of minimizers for convex integral functionals evaluated on linear differential operators of order one. This work intends to generalize the already existing theory for the cases of full and symmetric gradients to the entire class of ${\mathbb C}$-elliptic operators therein including the trace-free symmetric gradient for dimension $n \geq 3$.
Comparing MRI and conventional radiography for the detection of structural changes indicative of axial spondyloarthritis in the ASAS cohort
Authors: Protopopov Mikhail , Proft Fabian , Wichuk Stephanie , Machado Pedro M , Lambert Robert G , Weber Ulrich , Juhl Pedersen Susanne , Østergaard Mikkel , Sieper Joachim , Rudwaleit Martin , Baraliakos Xenofon , Maksymowych Walter P , Poddubnyy Denis
Published: August 2022

Objectives

To compare MRI and conventional radiography of SI joints for detection of structural lesions typical for axial spondyloarthritis (axSpA).

Methods

Adult patients from the Assessment of SpondyloArthritis international Society (ASAS) cohort with symptoms suggestive of axSpA and both SI joint MRI and radiographs available for central reading were included. Radiographs were evaluated by three readers according to the modified New York (mNY) criteria grading system. The presence of structural damage on radiographs was defined as fulfilment of the radiographic mNY criterion and, additionally, a lower threshold for sacroiliitis of at least grade 2 unilaterally. MRI scans were assessed for the presence of structural changes indicative of axSpA by seven readers. Diagnostic performance [sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR−)] of MRI and radiographs (vs rheumatologist’s diagnosis of axSpA) were calculated.

Results

Overall, 183 patients were included and 135 (73.7%) were diagnosed with axSpA. Structural lesions indicative of axSpA on MRI had sensitivity 38.5%, specificity 91.7%, PPV 92.9%, NPV 34.6%, LR+ 4.62 and LR− 0.67. Sacroiliitis according to the mNY criteria had sensitivity 54.8%, specificity 70.8%, PPV 84.1%, NPV 35.8%, LR+ 1.88 and LR− 0.64. Radiographic sacroiliitis of at least grade 2 unilaterally had sensitivity 65.2%, specificity 50.0%, PPV 78.6%, NPV 33.8%, LR+ 1.30 and LR− 0.69.

Conclusion

Structural lesions of the SI joint detected by MRI demonstrated better diagnostic performance and better interreader reliability compared with conventional radiography.
The effect of group-based cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: a randomized controlled trial
Authors: Latocha Kristine M , Løppenthin Katrine B , Østergaard Mikkel , Jennum Poul J , Hetland Merete L , Røgind Henrik , Lundbak Tine , Midtgaard Julie , Christensen Robin , Esbensen Bente A
Published: August 2022

Objectives

The primary objective was to compare the effect of cognitive behavioural therapy for insomnia (CBT-I) to usual care on sleep efficiency, measured by polysomnography (PSG) immediately after the intervention at week 7. Secondary objectives included comparing the longer-term effect on sleep- and RA-related outcomes at week 26.

Methods

In a randomized controlled trial using a parallel group design, the experimental intervention was 6 weeks’ nurse-led group-based CBT-I; the comparator was usual care. Analyses were based on the intention-to-treat (ITT) principle; missing data were statistically modelled using repeated-measures linear mixed effects models adjusted for the level at baseline.

Results

The ITT population consisted of 62 patients (89% women), with an average age of 58 years and an average sleep efficiency of 83.1%. At primary end point, sleep efficiency was 88.7% in the CBT-I group, compared with 83.7% in the control group (difference: 5.03 [95% CI −0.37, 10.43]; P = 0.068) measured by PSG at week 7. Key secondary outcomes measured with PSG had not improved at week 26. However, for all the patient-reported key secondary sleep- and RA-related outcomes, there were statistically highly significant differences between CBT-I and usual care (P < 0.0001), e.g. insomnia (Insomnia Severity Index: −9.85 [95% CI −11.77, −7.92]) and the RA impact of disease (RAID: −1.36 [95% CI −1.92, −0.80]) at week 26.

Conclusion

Nurse-led group-based CBT-I did not lead to an effect on sleep efficiency objectively measured with PSG. However, CBT-I showed improvement on all patient-reported key secondary sleep- and RA-related outcomes measured at week 26.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT03766100.
Height Gain After Spinal Fusion for Idiopathic Scoliosis: Which Model Fits Best?
Authors: Ikwuezunma Ijezie , Wang Kevin , Raymond Seye , Badin Daniel , Kreulen R. Timothy , Jain Amit , Sponseller Paul D. , Margalit Adam
Published: August 2022

Background:

Patients will often inquire about the magnitude of height gain after scoliosis surgery. Several published models have attempted to predict height gain using preoperative variables. Many of these models reported good internal validity but have not been validated against an external cohort. We attempted to test the validity of 5 published models against an external cohort from our institution. Models included were Hwang, Van Popta, Spencer, Watanabe, and Sarlak models.

Methods:

We retrospectively queried our institution’s records from 2006 to 2019 for patients with adolescent idiopathic scoliosis treated with posterior spinal fusion. We recorded preoperative and postoperative variables including clinical height measurements. We also performed radiographic measurements on preoperative and postoperative radiographic studies. We then tested the ability of the models to predict height gain by evaluating Pearson correlation coefficient, root mean square error, Akaike Information Criterion for each model.

Results:

A total of 387 patients were included. Mean clinical height gain was 3.1 (±1.7) cm.

All models demonstrated a moderate positive Pearson correlation coefficient, except the Hwang model, which demonstrated a weak correlation. The Spencer model was the only model with acceptable root mean square error (≤0.5) and was also the best fitting with the lowest Akaike Information Criterion (−308). The mean differences in height gain predictions between all models except the Hwang model was ≤1 cm.

Conclusions:

Four of the 5 models demonstrated moderate correlation and had good external validity compared with their development cohorts. Although the Spencer model was the best fitting, the clinical significance of the difference in height predictions compared with other models was low. The Watanabe model was the second best fitting and had the simplest formula, making it the most convenient to use in a clinical setting. We offer a simplified equation to use in a preoperative clinical setting based on this data—ΔHeight (mm)=0.77*(preoperative coronal angle−postoperative coronal angle).

Level of Evidence:

Not Applicable.
Risk Factors for Avascular Necrosis After Closed Reduction for Developmental Dysplasia of the Hip
Authors: Bian Zhen , Guo Yuan , Lyu XueMin , Zhu ZhenHua , Yang Zheng , Wang YuKun
Published: August 2022

Background:

Avascular necrosis (AVN) is a major complication after closed reduction for developmental dysplasia of the hip. The factors that predispose to AVN remain controversial. The purpose of this study was to analyze the risk factors, especially patient factors, such as age at reduction, grade of dislocation, and ossific nucleus development, related to AVN.

Materials and Methods:

We retrospectively reviewed children with dysplasia of the hip treated by closed reduction between 1997 and 2006. AVN was evaluated using Salter criteria and Kalamchi and MacEwen classification. Related factors were analyzed.

Results:

One hundred and eight children (140 hips) with an average age of 16.6 months at closed reduction (range: 6-24 mo) were included in the study. For an average duration of 10.1 years (range 7–16 y) of follow-up, 44 hips (31.4%) developed AVN. Grade II or higher AVN occurred in 14 hips (10%). The incidence of AVN increased with the grade of dislocation (P=0.022) and underdevelopment of the ossific nucleus (P<0.001). Underdevelopment of the ossific nucleus was also found to be positively correlated with the dislocation grade (P=0.047). The age at the time of reduction, sex, and side were not significant factors. Children who underwent secondary operation were all older than 1 year at reduction.

Conclusions:

High-grade dislocation correlates with the underdevelopment of the ossific nucleus. Patients with these 2 characteristics are predisposed to AVN. As underdevelopment of the ossific nucleus occurred regardless of age, it is not advisable to delay reduction because it does not alter the AVN rate, and instead, it increases the secondary operation rate.

Level of Evidence:

Level IV case series.
Redislocation After Posteromedial Open Reduction in Developmental Dysplasia of the Hip: Analyzing the Risk Factors and Determining the Optimal Treatment Method
Authors: Gencer Batuhan , Doğan Özgür , Çulcu Ahmet , Biçimoğlu Ali
Published: August 2022

Background:

Redislocation, which is one of the most serious problems in developmental dysplasia of the hip (DDH), might occur because of several reasons. Regardless of the treatment, redislocations are reported to be associated with high complication rates in the literature. Our objective was to identify the risk factors for redislocation in the patients treated for DDH and to determine the optimal treatment method for redislocations.

Methods:

Patients with DDH who were treated with the limited posteromedial approach in our clinic between 1993 and 2021 and followed up prospectively were examined in this single-centered study. The participants were assigned into 2 groups: a study group consisting of 25 hips of 17 patients with redislocation and a control group consisting of 502 hips of 390 patients without redislocation. To determine the risk factors for redislocation, demographic data, known risk factors for DDH, preoperative Tönnis stage, and whether the capsule was opened or not were evaluated. To determine the optimal treatment method, a subgroup analysis based on applied treatment (closed reduction and cast replacement vs. repeating open reduction) was conducted, and recurrent redislocation, complication, and secondary surgery rates were evaluated.

Results:

Bilaterality and high-grade hip dislocations were found to be associated with higher odds ratio (OR) for redislocation [P=0.007, OR=3.64, 95% confidence interval (CI), 1.3 to 8.8; and P=0.006, OR=4.52, 95% CI, 1.37 to 14.91, respectively]. Recurrent redislocation and complication rates were found to be significantly higher in redislocations treated with closed reduction and cast replacement (P=0.007 and P=0.015, respectively).

Conclusions:

Bilaterality and higher preoperative Tönnis stage are critical risk factors for redislocation after open reduction in DDH. It should be kept in mind that closed reduction and cast replacement is associated with higher rates of recurrent redislocation and complications, and redislocation cases should be treated by repeating open reduction.

Level of Evidence:

Level II—therapeutic study.
Elimination of Herpes Simplex Virus-2 and Epstein-Barr Virus With Seraph 100 Microbind Affinity Blood Filter and Therapeutic Plasma Exchange: An Explorative Study in a Patient With Acute Liver Failure
Authors: Andermatt Rea , Bloemberg Guido V. , Ganter Christoph C. , Mueller Nicolas J. , Mueller Antonia M. S. , Muellhaupt Beat , Kielstein Jan T. , David Sascha
Published: August 2022

OBJECTIVES:

Herpes simplex virus (HSV)-2 is a rare cause of hepatitis that can lead to acute liver failure (ALF) and often death. The earlier the initiation of acyclovir treatment the better the survival. With regard to ALF, controlled randomized data support the use of therapeutic plasma exchange (TPE) both as bridge to recovery or transplantation—possibly by modulating the systemic inflammatory response and by replacing coagulation factors. Seraph 100 Microbind Affinity Blood Filter (Seraph; Ex Thera Medical, Martinez, CA), a novel extracorporeal adsorption device, removes living pathogens by binding to a heparin-coated surface was shown to efficiently clear HSV-2 particles in vitro. Here, we tested the combination of Seraph with TPE to reduce a massive HSV-2 viral load to reach a situation in that liver transplantation would be feasible.

DESIGN:

Explorative study.

SETTING:

Academic tertiary care transplant center.

PATIENT:

Single patient with HSV-2–induced ALF.

INTERVENTIONS:

TPE + Seraph 100 Microbind Affinity Blood Filter.

MEASUREMENTS AND MAIN RESULTS:

We report Seraph clearance data of HSV-2 and of Epstein-Barr virus (EBV) in vivo as well as total viral elimination by TPE. Genome copies/mL of HSV-2 and EBV in EDTA plasma were measured by polymerase chain reaction every 60 minutes over 6 hours after starting Seraph both systemically and post adsorber. Also, HSV-2 and EBV were quantified before and after TPE and in the removed apheresis plasma. We found a total elimination of 1.81 × e11 HSV-2 copies and 2.11 × e6 EBV copies with a single TPE (exchange volume of 5L; 1.5× calculated plasma volume). Whole blood clearance of HSV-2 in the first 6 hours of treatment was 6.64 mL/min (4.98–12.92 mL/min). Despite much lower baseline viremia, clearance of EBV was higher 36.62 mL/min (22.67–53.48 mL/min).

CONCLUSIONS:

TPE was able to remove circulating HSV-2 copies by 25% and EBV copies by 40% from the blood. On the other hand, clearance of HSV-2 by Seraph was clinically irrelevant, but Seraph seemed to be far more effective of removing EBV, implicating a possible use in EBV-associated pathologies, but this requires further study.
Regulated cell death in cancer: from pathogenesis to treatment
Authors: Gong Linjing , Huang Dong , Shi Yujun , Liang Zong’an , Bu Hong
Published: August 2022

Regulated cell death (RCD), including apoptosis, pyroptosis, necroptosis, and ferroptosis, is regulated by a series of evolutionarily conserved pathways, and is required for development and tissue homeostasis. Based on previous genetic and biochemical explorations of cell death subroutines, the characteristics of each are generally considered distinctive. However, recent in-depth studies noted the presence of crosstalk between the different forms of RCD; hence, the concept of PANoptosis appeared. Cancer, a complex genetic disease, is characterized by stepwise deregulation of cell apoptosis and proliferation, with significant morbidity and mortality globally. At present, studies on the different RCD pathways, as well as the intricate relationships between different cell death subroutines, mainly focus on infectious diseases, and their roles in cancer remain unclear. As cancers are characterized by dysregulated cell death and inflammatory responses, most current treatment strategies aim to selectively induce cell death via different RCD pathways in cancer cells. In this review, we describe five types of RCD pathways in detail with respect to tumorigenesis and cancer progression. The potential value of some of these key effector molecules in tumor diagnosis and therapeutic response has also been raised. We then review and highlight recent progress in cancer treatment based on PANoptosis and ferroptosis induced by small-molecule compounds, immune checkpoint inhibitors, and nanoparticles. Together, these findings may provide meaningful evidence to fill in the gaps between cancer pathogenesis and RCD pathways to develop better cancer therapeutic strategies.
Roles of organelle-specific autophagy in hepatocytes in the development and treatment of non-alcoholic fatty liver disease
Authors: Zhang Yizhi , Chen Yu
Published: August 2022

Non-alcoholic fatty liver disease (NAFLD) is a disorder of lipid metabolism. The lipotoxic intermediates of lipid metabolism cause mitochondrial dysfunction and endoplasmic reticulum stress. Organelle-specific autophagy is responsible for the removal of dysfunctional organelles to maintain intracellular homeostasis. Lipophagy contributes to lipid turnover by degrading lipid droplets. The level of autophagy changes during the course of NAFLD, and the activation of hepatocyte autophagy might represent a method of treating NAFLD.
Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma
Authors: Xie Bangxiang , Hao Qian , Zhou Xiang , Chen Dexi
Published: August 2022

Background:

The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-encoding gene, however, is frequently mutated or deleted as the cancer progresses to the late stage and, under such circumstance, the p53 homolog TAp63 can harness HCC growth by transactivating several important p53-target genes.

Methods:

To determine whether HBx regulates TAp63, we performed co-immunoprecipitation assay, real-time quantitative polymerase chain reaction, immunoblotting, and flow cytometry analysis in p53-null cancer cell lines, Hep3B and H1299.

Results:

HBx interacts with the transactivation domain of TAp63, as HBx was co-immunoprecipitated with TAp63 but not with ΔNp63. The interaction between HBx and TAp63 abolished transcriptional activity of TAp63, as evidenced by the reduction of the levels of its target genes p21 and PUMA, consequently leading to restricted apoptosis and augmented proliferation of HCC cells.

Conclusion:

HBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63.
Cardiac Mechanics in Altered Hormonal States as a Surrogate for Understanding the Effects of Transgender Hormone Therapy
Authors: Moudgal Rohitha , Peritz David C. , Turco John , Taub Cynthia
Published: August 2022

Transgender individuals are increasingly seeking the care of physicians to physically transition to their self-identified gender identity. Gender-affirming hormone therapy (GAHT) has significant endocrine effects which may have cardiovascular consequences, and cardiovascular disease in transgender individuals is a growing area of study. The effects of GAHT on cardiac mechanics have yet to be characterized, but there is existing literature regarding changes to cardiac mechanics in similar altered hormonal states. We reviewed this literature, with a focus on echocardiographic findings. We found variable results between studies of different methodologies. These include findings that supraphysiological levels of testosterone may impair cardiac mechanics, whereas estrogen-containing hormonal replacement therapy may improve diastolic echocardiographic parameters. In summary, there are alterations to echocardiographic parameters in altered endocrine states related to exogenous testosterone and estrogen, in a manner that is likely dose-dependent. Encouragingly, the studies we reviewed did not suggest that hormonal changes within physiologic ranges would detrimentally affect echocardiographic parameters of systolic and diastolic function. Future research into the cardiovascular effects of long-term GAHT is warranted to safely guide the longitudinal treatment of transgender individuals.
Occupational risk factors for hypertension
Authors: Kang Mo-Yeol
Published: August 2022

The identification and characterization of the modifiable risk factors of hypertension is of great value for public health and clinical medicine to achieve primary prevention. A large amount of literature on the effects of occupational factors on blood pressure and hypertension has been published. In this review, I summarize current evidence regarding the role of occupational factors in hypertension. The results of this review suggest that there is sufficient evidence to support the association between increased risk of hypertension and job stress, shift work, occupational lead exposure, and noise exposure. The association of hypertension with physical inactivity, sedentary behavior, and occupational exposure to mercury, arsenic, cadmium, or carbon disulfide remains inconclusive, although several studies have reported this finding. This review will serve as a step toward future research and provide baseline information for developing strategic interventions to prevent hypertension in the working population.
Essential genomic knowledge in graduate nursing practice
Authors: Connors Laurie M. , Schirle Lori , Dietrich Mary S.
Published: August 2022

Background:

Genetics-informed nursing is essential to personalized health care. Advanced practice nurses will increasingly encounter genomic information in clinical care and are expected to have competency.

Purpose:

To examine genomic competency of advanced practice nursing students and faculty in a graduate nursing school.

Methods:

A convenience sample of graduate nursing faculty and students were electronically sent a survey assessing genomic knowledge. In total, 13.98% of faculty (33/236) and 9.87% of students (82/831) completed a demographic questionnaire, perceived genomic competency items, and Genomic Nursing Concept Inventory (GNCI). The GNCI is a 31-question multiple choice questionnaire assessing 18 genomic concepts in four categories (Human Genome Basics, Mutations, Inheritance Patterns, and Genomic Health care). Percentage of correct items was calculated for faculty and students, as were correlations between demographics, perceived genomic competency, and GNCI scores.

Results:

Students' GNCI overall scores were higher than faculty, 54.8% (interquartile range [IQR] 38–72%) vs 48.4% (IQR 32–68%). Both groups demonstrated the lowest scores in Genomic Basics (students 41.7% [IQR 25–67%] and faculty 33.3% [IQR 16–50%]). Students' and faculty's perceived genomic competency correlated with GNCI scores (r = 0.49, p < .001 and r = 0.70, p < .001, respectively). Age (r = −0.40, p < .001), entering nursing school after 2010 (r = 0.47, p < .001), and previous genomics course (r = 0.52, p < .001) were significantly correlated with GNCI total score for students, but not faculty.

Conclusions:

This study indicates that faculty and students in a graduate nursing school perceive and demonstrate low genomic knowledge, particularly in basic genomics. Further exploration into innovative methods to provide basic genomic education is needed.

Implications:

To provide access and equity for personalized genomic-based health care, we must prepare genomics-informed nurses.
Intra‐rater Variability of the Brussels Infants and Toddlers Stool Scale (BITSS) Using Photographed Stools
Authors: Hofman Yvonne Marianne Christine , Vandenplas Yvan , Ludwig Thomas , Ouald Chaib Abdelhalim , Kluyfhout Sandra , Krikilion Jasmina , De Geyter Charlotte , Huysentruyt Koen
Published: August 2022

Objectives:

The Brussels Infants and Toddlers Stool Scale (BITSS) was developed for the assessment of stool consistency in non–toilet‐trained children. This study aimed to (1) investigate the intra‐rater reliability of the BITSS among health care professionals (HCPs) and caregivers (CGs); (2) study a potential learning curve; (3) explore the impact of photo quality on intra‐rater reliability.

Methods:

Photos of diapers containing stool were assessed twice by 4 HCP (2432 photos) and 8 CGs (492 photos) using the BITTS. Intra‐rater reliability was calculated by the percentage of exact agreement and a κ‐value. A learning effect and the impact of photo quality was explored using mixed linear model and generalized estimating equations.

Results:

HCPs generated 24,320 stool consistency ratings: 12.1% were scored as watery, 31.0% loose, 29.4% formed, and 27.6% hard. CGs performed 7872 ratings: 9.2% classified as watery, 34.6% loose, 28.9% formed, and 27.3% hard. Intra‐rater reliability (κ) for HCPs ranged from 0.64 [95% confidence interval (CI) = 0.61–0.66] to 0.78 (95% CI = 0.76–0.80) and from 0.68 (95% CI = 0.63–0.73) to 0.94 (95% CI = 0.91–0.97) in the CG group. Both groups had <1% improvement in the odds of identical classification per 50 photos. The percentage of absolute agreement was higher in photos rated as good quality than those that were not (HCPs: 80.3% vs 69.5%, P < 0.001; CGs: 90.4% vs 86.3%, P < 0.001).

Conclusions:

The BITSS has an excellent intra‐rater reliability for the stool consistency scoring of photographs of stools in diapers, but can be influenced by photo quality. A clinically meaningless learning effect was found.
Obesity Paradox
Authors: Khalooeifard Razieh , Hemmati Amirhossein , Izadi Neda , Clark Cain , Hashemian Seyed Mohammad Reza , Emam Masoumeh Hosseinzadeh , Moghaddam Omid Moradi , Amirsavadkouhi Ali
Published: August 2022

A prominent issue for patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is obesity. Some reports claim that obese patients with acute respiratory distress syndrome have better outcomes. This inverse relationship has been termed the obesity paradox and is not yet understood in patients with coronavirus disease 2019 (COVID-19) hospitalized in the intensive care unit (ICU). The aim of this study was to investigate the obesity paradox in patients with COVID-19 admitted to the ICU. In this retrospective observational study, 5230 patients with COVID-19, admitted to the ICU between June 1, 2020, and January 10, 2021, were analyzed. Body mass index (BMI) was calculated according to the World Health Organization classification, and patients were categorized as underweight, normal, overweight, or obese for statistical analysis. A Kaplan-Meier survival analysis, Cox regression model, and dose-response relationship between BMI level and ICU length of stay (LOS) and connection to the ventilator survival were conducted. Of the 5230 patients studied, 3233 (62%) had nonobese BMIs, and 2997 (38%) were obese. We found no significant difference in mortality between obese and nonobese patients with COVID-19, where 1699 patients (31%) survived. However, there were significant differences in BMI level for ICU LOS and ventilation duration (P < 0.05, P < 0.03). In multivariable Cox regression, significant differences were observed in ICU LOS and ventilation duration of patients between obese and nonobese patients (P < 0.001, P < 0.005). There was no association between BMI and survival among patients with LOS in the ICU LOS or connection to a ventilator. However, obese patients with COVID-19 require more care than nonobese patients because of additional comorbidities, higher inflammation, and a weaker immune system.
Angiosarcoma-like Kaposi Sarcoma
Authors: Plaza Jose A. , Sangueza Omar P. , Giubellino Alessio , Gru Alejandro A. , Kaffenberger Benjamin , Wakely Paul E. , Sangueza Martin J.
Published: August 2022

Kaposi sarcoma (KS) is a rare low-grade angioproliferative neoplasm associated with human herpesvirus 8 (HHV-8) infection with multiple clinical subtypes and varying histopathologic patterns. Histologically, many different variants of KS have been reported, yet all can be difficult to recognize and must be differentiated from other vascular tumors. In this report, we studied fourteen cases of a newly described variant of KS reminiscent of a well-differentiated angiosarcoma (angiosarcoma-like KS). All cases showed a diffuse, ill-defined infiltrative dermal-based lesion composed of numerous anastomosing vascular channels of varying caliber lined by a single layer of endothelium with minimal pleomorphism. The vascular proliferation ramified through the dermis and dissected the collagen bundles along with infiltration into the subcutaneous fat and around skin appendages. All cases showed expression of vascular markers (CD31, CD34, and ERG) and were positive for HHV-8. None showed the classic histopathology associated with KS. Without clinical guidance these tumors can be difficult to recognize as KS, creating significant diagnostic challenges. Our study expands on a rare histologic variant of KS that ought to be considered in the differential diagnosis of any cutaneous well-differentiated angiosarcoma. Awareness of this variant of KS is of important for proper diagnosis and management of these patients; thus, careful attention to the histomorphology and clinical history can help lead the pathologist to the correct diagnosis.
Patient Safety Training Programs for Health Care Professionals: A Scoping Review
Authors: Amaral Catarina , Sequeira Carlos , Albacar-Riobóo Núria , Coelho Joana , Pinho Lara Guedes , Ferré-Grau Carme
Published: August 2022

Objective

This study aimed to map the evidence available on patient safety training programs for health professionals.

Methods

A scoping review was carried out. Several studies published between January 2010 and March 2020 in the following databases were investigated: CINAHL; MEDLINE; Nursing & Allied Health Collection: Comprehensive; Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; Cochrane; MedicLatina, via EBSCOhost; World Health Organization; Google Scholar; BVS—Biblioteca Virtual da Saúde; PubMed; B-On; and RCAAP—Repositórios Científicos de Acesso Aberto de Portugal.

Results

A total of 2841 articles were found, 7 were included. Most studies report that the development of patient safety programs for health care professionals provides them with tools and techniques to recognize adverse incidents induced by the professional system/practice; recognize human factors related to patient safety, such as nontechnical skills or tiredness; understand high-risk clinical processes; develop strategies that influence and enhance patient safety culture; promote communication, teamwork, and organizational culture concerning patient safety; analyze other characteristic and emerging topics in patient safety; and develop project proposals to improve patient safety, allowing health care professionals to consolidate their knowledge, leading initiatives to improve patient safety.

Conclusions

There are still few studies that test patient safety training programs, which is a concern given the importance of implementing safe practices. The existing evidence proves the efficacy of the training programs in improving patient safety, although there are some gaps.