bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescents’ Experiences of Idiopathic Scoliosis in the Presurgical Period: A Qualitative Study
Authors: Motyer Gillian S , Kiely Patrick J , Fitzgerald Amanda
Published: August 2021

Objective

Adolescent idiopathic scoliosis (AIS) is a sideways curvature of the spine that can progress severely during adolescent development and require surgical intervention. This qualitative study was conducted to explore the psychosocial experiences of adolescents with idiopathic scoliosis during the presurgical stage of treatment.

Methods

Fourteen adolescents with moderate-to-severe AIS aged 12–17 years participated in semistructured interviews and data were analyzed using inductive reflexive thematic analysis.

Results

Four key themes were generated from the analysis. “Proceeding with Caution” described adolescents’ adaptation to the physical impact of their AIS, while “Am I Different?” encompassed adolescents’ perceptions of their changing appearance and visibility of their condition. “An Emotional Journey” captured the rollercoaster of emotions from shock at diagnosis to the daunting realization of the severity of their condition, while knowing others with AIS could ease the emotional burden. Finally, adolescents’ concerns and expectations about their prospective surgery were captured by the theme “No Pain, No Gain”, whereby they were often keen to put surgery behind them.

Conclusions

Understanding and addressing adolescents’ psychosocial support needs as they manage the challenges associated with idiopathic scoliosis is a key component of promoting better outcomes among this patient group. Clinical implications and opportunities for support provision are discussed.
Antigen Test Performance Among Children and Adults at a SARS-CoV-2 Community Testing Site
Authors: Ford Laura , Whaley Melissa J , Shah Melisa M , Salvatore Phillip P , Segaloff Hannah E , Delaney Augustina , Currie Dustin W , Boyle-Estheimer Lauren , O’Hegarty Michelle , Morgan Clint N , Meece Jennifer , Ivacic Lynn , Thornburg Natalie J , Tamin Azaibi , Harcourt Jennifer L , Folster Jennifer M , Medrzycki Magdalena , Jain Shilpi , Wong Phili , Goffard Kimberly , Gieryn Douglas , Kahrs Juliana , Langolf Kimberly , Zochert Tara , Tate Jacqueline E , Hsu Christopher H , Kirking Hannah L
Published: August 2021

Background

Performance characteristics of SARS-CoV-2 antigen tests among children are limited despite the need for point-of-care testing in school and childcare settings. We describe children seeking SARS-CoV-2 testing at a community site and compare antigen test performance to real-time reverse transcription-polymerase chain reaction (RT-PCR) and viral culture.

Methods

Two anterior nasal specimens were self-collected for BinaxNOW antigen and RT-PCR testing, along with demographics, symptoms, and exposure information from individuals ≥5 years at a community testing site. Viral culture was attempted on residual antigen or RT-PCR-positive specimens. Demographic and clinical characteristics, and the performance of SARS-CoV-2 antigen tests, were compared among children (<18 years) and adults.

Results

About 1 in 10 included specimens were from children (225/2110); 16.4% (37/225) were RT-PCR-positive. Cycle threshold values were similar among RT-PCR-positive specimens from children and adults (22.5 vs 21.3, P = .46) and among specimens from symptomatic and asymptomatic children (22.5 vs 23.2, P = .39). Sensitivity of antigen test compared to RT-PCR was 73.0% (27/37) among specimens from children and 80.8% (240/297) among specimens from adults; among specimens from children, specificity was 100% (188/188), positive and negative predictive values were 100% (27/27) and 94.9% (188/198), respectively. Virus was isolated from 51.4% (19/37) of RT-PCR-positive pediatric specimens; all 19 had positive antigen test results.

Conclusions

With lower sensitivity relative to RT-PCR, antigen tests may not diagnose all positive COVID-19 cases; however, antigen testing identified children with live SARS-CoV-2 virus.
Recombination Facilitates Adaptive Evolution in Rhizobial Soil Bacteria
Authors: Cavassim Maria Izabel A , Andersen Stig U , Bataillon Thomas , Schierup Mikkel Heide
Published: August 2021

Homologous recombination is expected to increase natural selection efficacy by decoupling the fate of beneficial and deleterious mutations and by readily creating new combinations of beneficial alleles. Here, we investigate how the proportion of amino acid substitutions fixed by adaptive evolution (α) depends on the recombination rate in bacteria. We analyze 3,086 core protein-coding sequences from 196 genomes belonging to five closely related species of the genus Rhizobium. These genes are found in all species and do not display any signs of introgression between species. We estimate α using the site frequency spectrum (SFS) and divergence data for all pairs of species. We evaluate the impact of recombination within each species by dividing genes into three equally sized recombination classes based on their average level of intragenic linkage disequilibrium. We find that α varies from 0.07 to 0.39 across species and is positively correlated with the level of recombination. This is both due to a higher estimated rate of adaptive evolution and a lower estimated rate of nonadaptive evolution, suggesting that recombination both increases the fixation probability of advantageous variants and decreases the probability of fixation of deleterious variants. Our results demonstrate that homologous recombination facilitates adaptive evolution measured by α in the core genome of prokaryote species in agreement with studies in eukaryotes.
Genome Fractionation and Loss of Heterozygosity in Hybrids and Polyploids: Mechanisms, Consequences for Selection, and Link to Gene Function
Authors: Janko Karel , Bartoš Oldřich , Kočí Jan , Roslein Jan , Drdová Edita Janková , Kotusz Jan , Eisner Jan , Mokrejš Martin , Štefková-Kašparová Eva
Published: August 2021

Hybridization and genome duplication have played crucial roles in the evolution of many animal and plant taxa. The subgenomes of parental species undergo considerable changes in hybrids and polyploids, which often selectively eliminate segments of one subgenome. However, the mechanisms underlying these changes are not well understood, particularly when the hybridization is linked with asexual reproduction that opens up unexpected evolutionary pathways.

To elucidate this problem, we compared published cytogenetic and RNAseq data with exome sequences of asexual diploid and polyploid hybrids between three fish species; Cobitis elongatoides, C. taenia, and C. tanaitica. Clonal genomes remained generally static at chromosome-scale levels but their heterozygosity gradually deteriorated at the level of individual genes owing to allelic deletions and conversions. Interestingly, the impact of both processes varies among animals and genomic regions depending on ploidy level and the properties of affected genes. Namely, polyploids were more tolerant to deletions than diploid asexuals where conversions prevailed, and genomic restructuring events accumulated preferentially in genes characterized by high transcription levels and GC-content, strong purifying selection and specific functions like interacting with intracellular membranes. Although hybrids were phenotypically more similar to C. taenia, we found that they preferentially retained C. elongatoides alleles. This demonstrates that favored subgenome is not necessarily the transcriptionally dominant one.

This study demonstrated that subgenomes in asexual hybrids and polyploids evolve under a complex interplay of selection and several molecular mechanisms whose efficiency depends on the organism’s ploidy level, as well as functional properties and parental ancestry of the genomic region.
MitoPhen database: a human phenotype ontology-based approach to identify mitochondrial DNA diseases
Authors: Ratnaike Thiloka E , Greene Daniel , Wei Wei , Sanchis-Juan Alba , Schon Katherine R , van den Ameele Jelle , Raymond Lucy , Horvath Rita , Turro Ernest , Chinnery Patrick F
Published: August 2021

Diagnosing mitochondrial disorders remains challenging. This is partly because the clinical phenotypes of patients overlap with those of other sporadic and inherited disorders. Although the widespread availability of genetic testing has increased the rate of diagnosis, the combination of phenotypic and genetic heterogeneity still makes it difficult to reach a timely molecular diagnosis with confidence. An objective, systematic method for describing the phenotypic spectra for each variant provides a potential solution to this problem. We curated the clinical phenotypes of 6688 published individuals with 89 pathogenic mitochondrial DNA (mtDNA) mutations, collating 26 348 human phenotype ontology (HPO) terms to establish the MitoPhen database. This enabled a hypothesis-free definition of mtDNA clinical syndromes, an overview of heteroplasmy-phenotype relationships, the identification of under-recognized phenotypes, and provides a publicly available reference dataset for objective clinical comparison with new patients using the HPO. Studying 77 patients with independently confirmed positive mtDNA diagnoses and 1083 confirmed rare disease cases with a non-mitochondrial nuclear genetic diagnosis, we show that HPO-based phenotype similarity scores can distinguish these two classes of rare disease patients with a false discovery rate <10% at a sensitivity of 80%. Enriching the MitoPhen database with more patients will improve predictions for increasingly rare variants.
Transitioning to molecular diagnostics in pediatric high-grade glioma: experiences with the 2016 WHO classification of CNS tumors
Authors: Baugh Joshua N , Gielen Gerrit H , van Vuurden Dannis G , Veldhuijzen van Zanten Sophie E M , Hargrave Darren , Massimino Maura , Biassoni Veronica , Morales la Madrid Andres , Karremann Michael , Wiese Maria , Thomale Ulrich , Janssens Geert O , von Bueren André O , Perwein Thomas , Hoving Eelco W , Pietsch Torsten , Andreiuolo Felipe , Kramm Christof M
Published: August 2021

Background

Pediatric neuro-oncology was profoundly changed in the wake of the 2016 revision of the WHO Classification of Tumors of the Central Nervous System. Practitioners were challenged to quickly adapt to a system of tumor classification redefined by molecular diagnostics.

Methods

We designed a 22-question survey studying the impact of the revised WHO classification on pediatric high-grade glioma. The survey collected basic demographics, general attitudes, issues encountered, and opinions on pediatric subtypes. Participant answers were analyzed along socioeconomic lines utilizing the human development index (HDI) of the United Nations and membership in the group of seven (G7) world economic forum.

Results

Four hundred and sixty-five participants from 53 countries were included, 187 pediatric neurooncologists (40%), 160 neuropathologists (34%), and 118 other experts (26%). When asked about pediatric high-grade glioma entities, participants from very high development countries preferred treating a patient based on genetic findings. Participants from high and medium development countries indicated using traditional histology and tumor location as mainstays for therapeutic decisions. Non-G7 countries tended to regard the introduction of molecularly characterized tumor entities as a problem for daily routine due to lack of resources.

Conclusions

Our findings demonstrate an overall greater reliance and favorability to molecular diagnostics among very high development countries. A disparity in resources and access to molecular diagnostics has left some centers unable to classify pediatric high-grade glioma per the WHO classification. The forthcoming edition should strain to abate disparities in molecular diagnostic availability and work toward universal adaptation.
Cross-Neutralizing Activity Against SARS-CoV-2 Variants in COVID-19 Patients: Comparison of 4 Waves of the Pandemic in Japan
Authors: Furukawa Koichi , Tjan Lidya Handayani , Sutandhio Silvia , Kurahashi Yukiya , Iwata Sachiyo , Tohma Yoshiki , Sano Shigeru , Nakamura Sachiko , Nishimura Mitsuhiro , Arii Jun , Kiriu Tatsunori , Yamamoto Masatsugu , Nagano Tatsuya , Nishimura Yoshihiro , Mori Yasuko
Published: August 2021

Background

As of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but has not been firmly established.

Methods

We investigated the neutralizing potency of 81 coronavirus disease 2019 (COVID-19) patients’ sera from the first to fourth waves of the pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses.

Results

Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the fourth wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less severe patients was lower than that of more severe patients for all variants.

Conclusions

The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific to B.1.1.7 in the fourth wave suggests that mutations in the virus might cause conformational change of its spike protein, which affects immune recognition of D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.
A Fistful of Dollars: Financial Incentives, Peer Information, and Retirement Savings
Authors: Bauer Rob , Eberhardt Inka , Smeets Paul
Published: August 2021

To understand what motivates individuals to look at their pension situation and make adequate savings decisions, we conduct two field experiments with 226,946 and 257,433 pension fund participants. We find peer-information statements do not increase the rate at which individuals check their pension information, but lottery-type financial incentives do. Offering a few large prizes rather than many small prizes is most effective. However, the uptake of pension information does not lead to improved pension knowledge nor to increased self-reported savings three weeks after our intervention.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Effect of short-term high tryptophan diet fed to sows on their subsequent piglet behavior
Authors: Lay Donald C , Enneking Stacey A , Anderson Nichole C , Richert Brian T , Sapkota Avi
Published: August 2021

Housing sows in groups create the challenge of decreasing fighting amongst sows. One proposed method to do so is to feed a high tryptophan diet, but the effect on the fetus is unknown. To investigate this, 66 sows were fed one of three diets: Control (0.14% SID tryptophan), Medium (0.28% SID tryptophan), or High (0.42% SID tryptophan), from days 28 to 35 of gestation. Sows gestated in standard gestation stalls. Blood samples were taken on day 27 prior to and on day 35 after tryptophan supplementation. On days 1, 2, and 3, nursing bouts were observed so as to record disputes and displacements from teat competition. The piglets’ activity and fighting were recorded on days 3, 7, and 11 from 0700 to 1700 h. On day 12, four piglets per litter were blood sampled: two to be used in later behavior tests and two to act as controls for blood cortisol levels. On day 14, the two behavior test piglets from each litter were subjected to a 10-min Isolation Test and 5-min Human Approach Test. On day 15, the behavior test piglets were paired by sex and treatment (for example, a male Medium piglet paired with another male Medium piglet from a different crate) and each pair was subjected to a 10-min Social Challenge Test and immediately blood sampled. Piglet cortisol and serotonin did not differ among treatments (P > 0.10). There were no differences (P > 0.10) for number born (12.7 ± 0.4), born alive (11.7 ± 0.4), or mortality (1.1 ± 0.2). Behavior during nursing bouts was similar, with no treatment differences in number of disputes or displacements, and similar bout lengths among treatments (199.5 ± 4.6 s, P > 0.10). No differences were detected for any of the variables for Isolation or the Human Approach Tests (P > 0.10). During the Social Challenge Test, High piglets had more contacts approaching the head of the companion piglet than did either Medium or Control piglets (14.3 ± 1.1, 10.7 ± 1.1, and 9.69 ± 0.8, respectively, P < 0.02). Total number of aggressive interactions during the test tended to be greater for Medium piglets compared to High piglets (9.3 ± 1.5 vs 5.1 ± 0.9, P < 0.07). Time budget data of the litter indicate that piglets from all three treatments spent equal amounts of time active and inactive (P > 0.10). Aggression was low with 0.3 ± 0.04% of piglets displaying aggressive behavior. Feeding high concentrations of tryptophan for a short duration early in gestation does not have a negative impact on sows’ subsequent offspring.
Transcriptome‐based insights into gene networks controlling myopia prevention
Authors: Karouta Cindy , Kucharski Robert , Hardy Kristine , Thomson Kate , Maleszka Ryszard , Morgan Ian , Ashby Regan
Published: August 2021

Myopia (short‐sightedness), usually caused by excessive elongation of the eye during development, has reached epidemic proportions worldwide. In animal systems including the chicken model, several treatments have been shown to inhibit ocular elongation and experimental myopia. Although diverse in their apparent mechanism of action, each one leads to a reduction in the rate of ocular growth. We hypothesize that a defined set of retinal molecular changes may underlie growth inhibition, irrespective of the treatment agent used. Accordingly, across five well‐established but diverse methods of inhibiting myopia, significant overlap is seen in the retinal transcriptome profile (transcript levels and alternative splicing events) in chicks when analyzed by RNA‐seq. Within the two major pathway networks enriched during growth inhibition, that of cell signaling and circadian entrainment, transcription factors form the largest functional grouping. Importantly, a large percentage of those genes forming the defined retinal response are downstream targets of the transcription factor EGR1 which itself shows a universal response to all five growth‐inhibitory treatments. This supports EGR1's previously implicated role in ocular growth regulation. Finally, by contrasting our data with human linkage and GWAS studies on refractive error, we confirm the applicability of our study to the human condition. Together, these findings suggest that a universal set of transcriptome changes, which sit within a well‐defined retinal network that cannot be bypassed, is fundamental to growth regulation, thus paving a way for designing novel targets for myopia therapies.
Isolation of human fibroadipogenic progenitors and satellite cells from frozen muscle biopsies
Authors: Suárez‐Calvet Xavier , Fernández‐Simón Esther , Piñol‐Jurado Patricia , Alonso‐Pérez Jorge , Carrasco‐Rozas Ana , Lleixà Cinta , López‐Fernández Susana , Pons Gemma , Soria Laura , Bigot Anne , Mouly Vincent , Illa Isabel , Gallardo Eduard , Jaiswal Jyoti K. , Díaz‐Manera Jordi
Published: August 2021

Skeletal muscle contains multiple cell types that work together to maintain tissue homeostasis. Among these, satellite cells (SC) and fibroadipogenic progenitors cells (FAPs) are the two main stem cell pools. Studies of these cells using animal models have shown the importance of interactions between these cells in repair of healthy muscle, and degeneration of dystrophic muscle. Due to the unavailability of fresh patient muscle biopsies, similar analysis of interactions between human FAPs and SCs is limited especially among the muscular dystrophy patients. To address this issue here we describe a method that allows the use of frozen human skeletal muscle biopsies to simultaneously isolate and grow SCs and FAPs from healthy or dystrophic patients. We show that while the purified SCs differentiate into mature myotubes, purified FAPs can differentiate into adipocytes or fibroblasts demonstrating their multipotency. We find that these FAPs can be immortalized and the immortalized FAPs (iFAPs) retain their multipotency. These approaches open the door for carrying out personalized analysis of patient FAPs and interactions with the SCs that lead to muscle loss.
Review of pediatric functional outcomes measures used to evaluate surgical management in pediatric patients with an upper extremity fracture
Authors: Alberghina Flavia , Andreacchio Antonio , Pavone Vito , Mansour Mounira , Dimeglio Alain , Canavese Federico
Published: August 2021

For two decades, many scores, questionnaires, and rating systems have been used to evaluate the functional outcome of children with an upper extremity fracture (UEF). However, only a few of these were created specifically for children, and many assess only elbow function. In the absence of any published review on this topic, we set out to identify and categorize different scores used to evaluate the clinical and functional outcomes of surgically treated pediatric UEFs. A literature search was performed, and 38 studies were identified. The scores used more often were the shortened version of the Disability of the Arm, Shoulder and Hand questionnaire and the Mayo Elbow Performance Score/Index. In a lower number of studies, authors used other scoring systems, including the Mayo Wrist Score, the Patient-Rated Wrist Evaluation, the Patient-Rated Elbow Evaluation, the Métaizeau functional scoring system, the Oxford Elbow Score, the Price and Flynn criteria, the Hardacre Functional Score, the Neer Shoulder Score, the Constant-Murley Shoulder Score, the Modified Orthopedic Trauma Association Score, the Medical Outcomes Study Short Form-36, and the Pediatric Outcomes Data Collection Instrument. Some specific pediatric scoring systems to evaluate the functional outcome of children with a UEF have been suggested, but a single tool that is valid and reliable for skeletally immature patients of all ages is not yet available. Further studies are needed to identify specific pediatric measurements to increase validity, responsiveness, sensitivity, and interpretability of upper limb functional outcome scores in common clinical practice.
Multi-day delay to care identified in pediatric trauma cases during COVID-19
Authors: Shaw Kylie G. , Salton Reba L. , Carry Patrick , Hadley-Miller Nancy , Georgopoulos Gaia
Published: August 2021

This study aims to establish how pediatric fracture patterns were altered at a level 1 trauma center in a state that implemented a shutdown during the initial height of COVID-19. After IRB approval, we identified 2017 patients treated at a pediatric institution for definitive management of a fracture between 26 March and 31 May 2018, 2019, or 2020. Dates were chosen based on statewide stay-at-home orders for Colorado. Patients were excluded for treatment at another institution (n = 148), no fracture noted in clinic (n = 18), or other (n = 13). Data were retrospectively collected from the remaining 1838 patients regarding demographics, fracture injury, mechanism, and treatment. Odds ratios (ORs) were calculated for each variable during COVID-19 relative to prior years. The number of fractures during 2020 decreased by 26% relative to 2019 and 23% to 2018. A larger proportion of patients experienced at least a 5-day delay to definitive treatment [OR: 1.55, confidence interval (CI): 1.23–1.96, P = 0.0002]. Rates of non-accidental trauma (NAT) increased non-significantly (OR: 2.67, CI: 0.86–8.32, P = 0.0900) during 2020 (1.2%) relative to 2018 (0.6%) and 2019 (0.3%). Fractures occurring at home increased to 79.9% (OR: 6.44, CI: 5.04–8.22, P < 0.0001). Despite less overall trauma during shelter-in-place orders, greater fracture numbers were seen among younger children and severe fractures were likely among older children. Patients may hesitate to seek care during 2020. Rates of NAT doubled during 2020. As communities prepare for future waves, treatment centers should warn against common fracture mechanisms and raise awareness of NAT.
Knockdown of CXCL5 inhibits the invasion, metastasis and stemness of bladder cancer lung metastatic cells by downregulating CD44
Authors: Wang Weiyi , Zhang Mengzhao , Huang Zhixin , Wang Lu , Yue Yangyang , Wang Xinyang , Lu Shaoying , Fan Jinhai
Published: August 2021

In our previous studies, we found that T24 lung metastatic cancer cells showed high invasion and metastasis abilities and cancer stem cell characteristics compared with T24 primary cancer cells. By screening for the expression of CXC chemokines in both cell lines, we found that CXCL5 is highly expressed in T24-L cells. The aim of this study is to shed light on the relationship of CXCL5 with epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs). RNAi technology was used to decrease CXCL5 expression in the T24-L cell line, and the EMT and CSCs of the shCXCL5 group and the control group were compared. The CXCR2 inhibitor SB225002 was used to inhibit the receptor of CXCL5 to determine the effect of the CXCL5/CXCR2 axis. The knockdown of CXCL5 expression in T24-L cells reduced their EMT and CSC characteristics. RT-PCR and Western blot analyses revealed the downregulation of N-cadherin, Vimentin and CD44. In addition, when CD44 expression was knocked down, the EMT ability of the cells was also inhibited. This phenomenon was most pronounced when both CXCL5 and CD44 were knocked down. CXCL5 and CD44 can affect the EMT and stem cell capacity of T24-L cells through some interaction.
A case of polymorphic dermal angiitis in a B-cell chronic lymphocytic leukemia patient during rituximab therapy
Authors: Morozova Elena , Teplyuk Natalia , Grabovskaya Olga , Kayumova Lyailya , Smirnova Liudmila
Published: August 2021

The aim of the study is to describe a case is of clinical interest as the first known occurrence of skin vasculitis during rituximab treatment. The article describes a case of polymorphic dermal angiitis, a combination of hemorrhagic and ulcerative-necrotic forms against the background of rituximab treatment in a 53-year-old woman suffering from chronic lymphocytic leukemia (b-CLL). During four hours after the 5th intravenous administration of rituximab, the appearance of painful rashes on the skin of both shins of a patient was observed. In the following few days, a progression of the pathological skin process was noted. The treatment with prednisolone in the amount of 50 mg/day, amoxicillin and clavulanic acid in the amount of 1000 mg twice per day and Diflucan in a dosage of 50 mg/day for 15 days was prescribed. In a local therapy, wet-drying bandages with antiseptic solutions, combined topic glucocorticosteroid preparations, drugs that improve trophic and tissue regeneration were recommended. After discharge, the patient continued to receive prednisolone in the amount of 50 mg/day for 14 days with a slow decrease in the dosage of the drug until the withdrawal under the supervision of a dermatologist. The described experience of how combined forms of polymorphic dermal angiitis are developing can be considered a result of toxic drug response to rituximab.
HMGA1 promotes hepatocellular carcinoma proliferation, migration, and regulates cell cycle via miR-195-5p
Authors: Shi Minyang , Lv Xuyang , Zhu Mengqi , Dong Yue , Hu Linfeng , Qian Ying , Fan Chunlei , Tian Nan
Published: August 2021

HMGA1 has been reported to be aberrantly expressed and correlate with the poor prognosis of many carcinomas. This study aimed to investigate the clinical significance and molecular mechanism of HMGA1 as a tumor-suppressing gene in hepatocellular carcinoma (HCC). Analysis of TCGA dataset by TANRIC website and R2 platform, we found that HMGA1 expression was significantly higher in HCC tissues compared to that in normal liver tissues and was associated with Edmondson grade. Patients with highly expressed HMGA1 had worse overall survival. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis showed the potential relationships between HMGA1 and other genes in HCC. We also demonstrated that the downregulation of HMGA1 dramatically suppressed the proliferation and migration of HCC cells. Furthermore, ectopic expression of HMGA1 blocked G0/G1 to S transition. Subsequent investigation characterized HMGA1 as a direct target of miR-195-5p, and miR-195-5p downregulation abrogated the effect of HMGA1 on HCC proliferation, migration, and cell cycle arrest. In addition, we also demonstrated that miR-195-5p downregulation abrogated the effect of HMGA1 on HCC growth in vivo. Taken together, our data provide strong evidence that HMGA1 promotes HCC and is negatively regulated by the tumor-suppressor, miR-195-5p.
The power of kindness: curative treatment with metronomic combination in advanced hepatocellular carcinoma
Authors: Brandi Giovanni , Di Federico Alessandro , Rizzo Alessandro , De Lorenzo Stefania , Vasuri Francesco , Brocchi Stefano , Golfieri Rita , Morelli Maria Cristina , Frega Giorgio , Palloni Andrea
Published: August 2021

The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patient received metronomic capecitabine as upfront therapy. Due to the suspect of progressive disease at the first radiologic assessment, metronomic cyclophosphamide was added to capecitabine aiming to enhance its efficacy. After 4 months of treatment, complete tumor response, alpha-fetoprotein (AFP) normalization and the recovery of a Child-Pugh A were achieved. The patient was then able to undergo liver transplantation, and, after 18 months from the diagnosis, he is still free of disease recurrence. This experience emphasizes the reliability of metronomic capecitabine as a well-tolerated and effective treatment when patient’s conditions prevent the administration of standard first-line treatments. In fact, metronomic capecitabine demonstrated its effectiveness in advanced HCC in retrospective and prospective analyses, leading to median progression-free survival and overall survival of, respectively, 6.03 and 14.47 months in phase II single-arm trial. Moreover, in consideration of the raising interest in immune-checkpoint inhibition in HCC, we believe that the immunomodulating effects of metronomic chemotherapy, either capecitabine or cyclophosphamide, warrant future trials exploring its combination with immunotherapy.
PARP1 rs1136410 (A/G) polymorphism is associated with early age of onset of gallbladder cancer
Authors: Anjali Kumari , Singh Deepika , Kumar Puneet , Kumar Tarun , Narayan Gopeshwar , Singh Sunita
Published: August 2021

Objectives

Evaluation of the association of PARP1 rs1136410 (A/G) polymorphism with gallbladder cancer susceptibility and its prognosis in the Indian population of eastern Uttar Pradesh and western Bihar.

Methods

PARP1 rs1136410 was genotyped by PCR-RFLP and its association with the prognosis of gallbladder cancer patients were analyzed using Kaplan–Meier plot and log-rank tests.

Results

Our results demonstrate that minor allele G is more frequent in gallbladder cancer patients than controls. The frequencies of minor allele G and GG genotype are significantly associated with increased risk of gallbladder cancer. Our data suggest that the minor allele G and homozygous genotype GG are significant predisposing factors for the early age of onset of gallbladder cancer. Similarly, women patients having AG and GG genotypes demonstrate an increased risk of gallbladder cancer. The risk group genotypes (AG + GG) are significantly more frequent in patients with thick gallbladder wall, with jaundice and with the presence of lymph node than in patients with normal gallbladder wall thickness, without jaundice and absence of lymph node involvement. Survival analysis data suggest that patients with risk group genotype (AG + GG) presenting jaundice have shorter overall survival.

Conclusion

Our study suggests that the minor allele G of PARP1 rs1136410 (A/G) is a predisposing factor for gallbladder carcinogenesis and is significantly associated with early onset of the disease. Interestingly, the minor allele G is significantly more frequent in the patients with jaundice, lymph node metastasis and gallbladder wall thickness.
Long-term Overall Survival and Predictors in Anti–PD-1-naive Melanoma Patients With Brain Metastases Treated With Immune Checkpoint Inhibitors in the Real-world Setting: A Multicohort Study
Authors: Naik Girish S. , Buchbinder Elizabeth I. , Cohen Justine V. , Manos Michael P. , Johnson Alistair E.W. , Bowling Peter , Aizer Ayal A. , Schoenfeld Jonathan D. , Lawrence Donald P. , Haq Rizwan , Hodi Frank Stephen , Sullivan Ryan J. , Ott Patrick A.
Published: August 2021

Long-term survival outcomes among melanoma patients with brain metastases treated with immune checkpoint inhibitors are limited. In this retrospective study at 2 centers, metastatic melanoma patients with radiographic evidence of brain metastases who received anti–programmed death-1 (PD-1) monotherapy or nivolumab in combination with ipilimumab between 2014 and 2017 were included. Overall survival (OS) was assessed in diagnosis-specific graded prognostic assessment (ds-GPA) and melanoma–molecular graded prognostic assessment (molGPA) prognostic risk groups. Baseline clinical covariates were used to identify predictors of OS in univariate/multivariable Cox proportional-hazards models. A total of 84 patients (58 monotherapy, 26 combination) were included with a median duration of follow-up of 43.4 months (maximum: 5.1 y). The median OS [95% confidence interval (CI)] was 3.1 months (1.8, 7) for ds-GPA 0–1, 22.1 months [5.4, not reached (NR)] for ds-GPA 2 and NR (24.9, NR) for ds-GPA 3–4 in the monotherapy cohort [hazard ratio (HR) for ds-GPA 3–4 vs. 0–1: 0.13 (95% CI: 0.052, 0.32); 0.29 (95% CI: 0.12, 0.63) for ds-GPA 2 vs. 0–1]. The median OS was 1.1 months (95% CI: 0.3, NR) for ds-GPA 0–1, 11.8 months (95% CI: 2.9, 23.3) for ds-GPA 2 and 24.4 months (95% CI: 3.4, NR) for ds-GPA 3–4 in the combination cohort [HR for 3–4 vs. 0–1: 0.013 (95% CI: 0.0012, 0.14); HR for ds-GPA 2 vs. 0–1: 0.033 (0.0035, 0.31)]. Predictors associated with longer survival included ds-GPA or molGPA>1 (among prognostic indices), neutrophil-to-lymphocyte ratio (<4 vs. ≥4), while high lactate dehydrogenase, neurological symptoms, and leptomeningeal metastases were associated with shorter survival. Baseline ds-GPA/molGPA>1 and neutrophil-to-lymphocyte ratio <4 were strong predictors of long-term survival to anti–PD-1-based immune checkpoint inhibitors in melanoma brain metastases patients previously naive to anti-PD-1 therapy in a real-world clinical setting treated at independent centers.
Integrated Analysis Of Immunotherapy Treated Clear Cell Renal Cell Carcinomas: An Exploratory Study
Authors: Sobottka Bettina , Nienhold Ronny , Nowak Marta , Hench Juergen , Haeuptle Pirmin , Frank Angela , Sachs Melanie , Kahraman Abdullah , Moch Holger , Koelzer Viktor H. , Mertz Kirsten D.
Published: August 2021

Molecular or immunological differences between responders and nonresponders to immune checkpoint inhibitors (ICIs) of clear cell renal cell carcinomas (ccRCCs) remain incompletely understood. To address this question, we performed next-generation sequencing, methylation analysis, genome wide copy number analysis, targeted RNA sequencing and T-cell receptor sequencing, and we studied frequencies of tumor-infiltrating CD8+ T cells, presence of tertiary lymphoid structures (TLS) and PD-L1 expression in 8 treatment-naive ccRCC patients subsequently treated with ICI (3 responders, 5 nonresponders). Unexpectedly, we identified decreased frequencies of CD8+ tumor-infiltrating T cells and TLS, and a decreased expression of PD-L1 in ICI responders when compared with nonresponders. However, neither tumor-specific genetic alterations nor gene expression profiles correlated with response to ICI or the observed immune features. Our results underline the challenge to stratify ccRCC patients for immunotherapy based on routinely available pathologic primary tumor material, even with advanced technologies. Our findings emphasize the analysis of pretreated metastatic tissue in line with recent observations describing treatment effects on the tumor microenvironment. In addition, our data call for further investigation of additional parameters in a larger ccRCC cohort to understand the mechanistic implications of the observed differences in tumor-infiltrating CD8+ T cells, TLS, and PD-L1 expression.
Optimal Sampling Strategy and Threshold of Serum Vancomycin Concentration in Elderly Japanese Patients Undergoing High-Flux Hemodialysis
Authors: Ogawa Akio , Hira Daiki , Tsujimoto Masayuki , Nishiguchi Kohshi , Endo Masanori , Ono Toshiaki , Hatta Tsuguru , Terada Tomohiro , Morita Shin-ya
Published: August 2021

Background:

The optimal sampling points and thresholds for initial serum vancomycin (VCM) concentrations have not been determined in hemodialysis (HD) patients. To clarify this, multiple blood tests were performed, and the correlations between VCM concentrations at several sampling points and the area under the concentration–time curve for 24 hours (AUC24h) were analyzed.

Methods:

A single-center, prospective observational study was conducted. Patients with end-stage renal failure who received VCM treatment while undergoing chronic maintenance HD were enrolled in this study. HD was performed using a high-flux membrane as the dialyzer. After VCM administration, 7 points were sampled between the first and second HD. The AUC24h after the end of the first HD (AUC0–24) and that before the end of the second HD (AUC24–48) were calculated using the linear trapezoidal method. Correlation analysis and simple regression analysis between AUC24h and serum concentrations were performed at each sampling point.

Results:

Nine patients were evaluated. Strong correlations were found between AUC24–48 and serum concentrations at 24 hours after the initiation of VCM treatment following the first HD (C24h, R = 0.983 and P < 0.001), between AUC0–24 and C24h (R = 0.967 and P < 0.001), and between AUC24–48 and serum concentration just before the second HD (Cpre(HD2), R = 0.965 and P < 0.001). Regression equations with high coefficients of determination (R
2 > 0.9) were obtained, and a C24h of ≥18.0 mg/L and a Cpre(HD2) of ≥16.5 mg/L were required to achieve an AUC24–48 value of ≥400 mg·h/L. In addition, a C24h of ≤23.3 mg/L was estimated to satisfy the AUC0–24 range of ≤600 mg·h/L.

Conclusions:

C24h and Cpre(HD2) are optimal sampling points for predicting VCM-AUC24h in HD patients.
Nurses' Use of Spiritual Practices in Caring for Self During the Pandemic
Authors: Hawthorne Dawn M. , Barry Charlotte D.
Published: August 2021

Stressful life events often disrupt individuals' assumptive world, challenging their self-identity and altering their lives. Suffering from stressful life events may have a profound negative impact on a person's life. Nurses felt great demands on their spiritual selves even as they responded to the grave situations and caring demands needed to care for the spirits of their patients during the coronavirus (COVID-19) pandemic. However, with intentionality, suffering and stress can be ameliorated by engaging in spiritual self-care and self-renewing activities. Spirituality is recognized as an essential factor in a person's health and well-being and is integral to the process of growing through life events, such as illness, grief, and bereavement. Nurses may choose to use spiritual practices, either religious or nonreligious, to buffer the effects of stressful life events. The concept of caring for self has long being promoted, by scholars, as an essential need of nurses to care for themselves, not so they can keep on giving to others but because each nurse is worthy of being cared for by self. In the era of the pandemic in which stressful work environment, social distancing, and self-isolation make it difficult to maintain interconnectedness and build relationships, despair can occur. Spiritual practices are examples of the resources that can be used effectively in times of stress to reduce the negativity that life stressors create in individuals.
Biodanza as a Nonpharmacological Dance Movement–Based Treatment in Older People With Alzheimer's Disease
Authors: Chiesi Fabrizio , Gori Eleonora , Collini Francesca , Palfrader Angelo , Galli Roberto , Guazzini Andrea , Collodi Stefania , Lorini Chiara , Bonaccorsi Guglielmo
Published: August 2021

The aim of this pilot, feasibility study was to assess health improvements in 16 institutionalized older people with Alzheimer's disease, after the Biodanza intervention, a nonpharmacological dance movement-based treatment. Biodanza significantly decreased agitated and neuropsychiatric behaviors. Effectiveness studies will be performed in order to assess the implication of such interventions.
Solitary Extramedullary Plasmacytoma of the Lacrimal Sac With Associated Crystal-Storing Histiocytosis
Authors: Lee Christine M. , Asilnejad Brenda , Cohen Liza M. , Roelofs Kelsey A. , Rootman Daniel B. , Khanlou Negar , Pullarkat Sheeja T.
Published: August 2021

Purpose:

To report a rare case of crystal-storing histiocytosis associated with solitary extramedullary plasmacytoma of the lacrimal sac and to review literature on the 2 entities to summarize important diagnostic, management, and prognostic considerations.

Methods:

A case report of the ophthalmologic presentation, pathology workup, and oncologic management is presented. Literature search with focus on lesions occurring in ophthalmic sites and management guidelines from expert panels and working groups.

Results:

Crystal-storing histiocytosis associated with solitary extramedullary plasmacytoma arose within the lacrimal sac of a previously healthy middle-aged woman and presented as a painless nodule with epiphora. The biopsy tissue showed sheets of crystal-filled histiocytes, interspersed with monoclonal plasma cells and rarely demonstrated plasma cell phagocytosis. Imaging and laboratory studies confirmed the localized nature.

Conclusions:

Crystal-storing histiocytosis is an uncommon entity in which crystals, most commonly arising from altered immunoglobulins, aggregate within histiocytes and form symptomatic mass lesions. It has been reported in ophthalmic regions in patients with a concurrent lymphoproliferative or plasma cell disorder and can rarely predate a malignancy. The current case is notable because crystal-storing histiocytosis occurs with a localized process, solitary extramedullary plasmacytoma, and presents in an unusual site, the lacrimal sac. Tissue biopsy with multimodal pathological evaluation is necessary to make the diagnosis. Ophthalmologists should recognize that crystal-storing histiocytosis is commonly associated with a hematologic malignancy and, when appropriate, refer the patient for oncologic management. Surveillance may be indicated in cases with no established etiology. Solitary extramedullary plasmacytoma should also be monitored, as a proportion of cases progress to multiple myeloma.
A prospective, randomized study assessing different modalities for flushing totally implanted vascular access device in children with malignancy
Authors: Hsieh Hsiang-Chen , Hung Shu-Chen , Huang Sheng-Yang , Huang Fang-Liang , Chou Chia-Man
Published: August 2021

Background:

The totally implanted vascular access device (TIVAD) is commonly used in patients with malignant tumors requiring chemotherapy or long-term intravenous infusion and those with difficulty placing peripheral venous catheters. It could also be used to draw blood in pediatric patients. Thus, how to maintain the patency and longevity of TIVAD is always emphasized.

Methods:

In this prospective study, TIVAD was randomly infused in patients under 18 years with three different concentrations of heparinized solutions: 10 mL with 100 U/mL heparin, 20 mL with 10 U/mL heparin, and 30 mL with 10 U/mL heparin.

Results:

A total of 81 patients (46 males and 35 females) were enrolled in this study from August 2, 2013 to February 1, 2017. The mean age of those who received TIVAD implantation was 7.2 ± 5.3 years, and the mean duration of using TIVAD was 1027.6 ± 369.1 days. Patients without catheter occlusion events experienced significantly shorter hospitalizations, fewer admissions, and fewer punctures than those with catheter occlusion events (p < 0.05). The administration and frequency of blood transfusions, history of bacteremia, and medication history did not increase the risk of catheter occlusion, but puncture frequency increased this risk. In patients with catheter occlusion events (38/81, 46.9%), catheter patency was restored after instillation of urokinase solution.

Conclusion:

In this study, the risk of TIVAD catheter occlusion was only related to puncture frequency regardless of the heparin flush composition or patient characteristics. A high puncture frequency of TIVAD during the 3.5-year study period significantly increased the risk of catheter occlusion. Besides, flushing and locking solutions for TIVAD using heparin at 10 U/mL was effective as using heparin at 100 U/mL regardless of the flushing volume of 10, 20, or 30 mL.
Multiple gastric artery aneurysms managed by transcatheter arterial embolization
Authors: Yang Junlin , Cai Wu , Fan Guohua , Zhai Duchang
Published: August 2021

Rationale:

Visceral artery aneurysms are very rare and carry a high risk of mortality. Gastric artery aneurysms (GAAs) account for less than 4% of visceral artery aneurysms. When the aneurysm ruptures, patients can present with epigastric pain, hematemesis, hematochezia, vomiting, hypotension, shock and other clinical manifestations.

Patient concerns:

We report a case of a 69-year-old man who presented with sudden abdominal pain, hypotension and melena.

Diagnoses:

Digestive tract hemorrhage secondary to one rupturing aneurysmamong three Gastric artery aneurysms.

Interventions:

Transcatheter arterial embolization with Gelatin Sponge Particle Embolic Agent, Glubran and an Embolization Microcoil was conducted to occlude the blood flow to the three GAAs.

Outcomes:

The patient returned safely to the ward without apparent complications and was discharged after eight days of hospitalization. At the 4-month follow-up, his condition remained stable, and there were no complications or symptoms observed.

Lessons:

Multiple GAAs are extremely rare and should be treated immediately. Transcatheter arterial embolization is the treatment for this rare lesion. Timely recognition and immediate treatment for ruptured GAAs usually results in a good prognosis.