bluuebunny/crossref_metadata_2025 huggingface dataset:
The missing slope: paradoxical shortening of activated partial thromboplastin time in a patient on unfractionated heparin therapy
Authors: Lapić Ivana , Lončar Vrančić Ana , Coen Herak Désirée , Rogić Dunja
Published: June 2021

This case report describes false shortening of activated partial thromboplastin time (aPTT) due to erroneous optical reading of the clotting point in the presence of unfractionated heparin (UFH), and a biphasic waveform. Activated partial thromboplastin time performed on a coagulometer with photo-optical detection yielded an ambiguous clotting curve characterized by an early and steady decrease in light transmittance throughout the whole measuring range, with the clotting point read at 65 seconds. Further investigations included measurement of aPTT by means of a mechanical clot detection method as well as determination of another heparin-sensitive coagulation assay, that is thrombin time (TT), both being unmeasurably prolonged (> 150 seconds). Communication with clinicians revealed that the patient was on continuous UFH therapy and had an underlying sepsis, with highly elevated C-reactive protein (289 mg/L). The aPTT measurements requested at three timepoints later during the same day revealed gradual aPTT shortening and unveiled a peculiar biphasic waveform pattern. In this case, unmeasurably prolonged aPTT due to UFH therapy was masked by a biphasic aPTT curve pattern making only the first slope of the biphasic waveform visible within the measuring range. The early decrease in plasma light transmittance mimicked optical changes related to clot formation, thus causing erroneous optical reading and yielding a falsely shortened aPTT. This case emphasizes that such a pattern should be carefully inspected, especially when a combination of a critically ill condition and UFH therapy is present, in order to prevent erroneous reporting of aPTT and potential adverse effects on patient care.
On Spinopilar from Rio de Janeiro state with description of three new species (Opiliones, Laniatores, Cryptogeobiidae)
Authors: KURY ADRIANO B. , ARAUJO DÉBORA C.
Published: June 2021

The genus Spinopilar Mello-Leitão, 1940 currently has seven species distributed in eastern Brazil, Argentina and Paraguay. Three species are hitherto known from Rio de Janeiro state (RJ), in the Brazilian Atlantic Forest. In this paper, five species from Rio de Janeiro state (RJ) are studied as follows: (1) Spinopilar armatus Mello-Leitão, 1940, the type species of Spinopilar, originally described without illustrations, is herein redescribed based on additional material from the metropolitan area of Rio de Janeiro city. (2) Spinopilar anomalis (Sørensen, 1932) is a species never recorded again after the original description. A new diagnosis is provided for S. anomalis based on a translation of the original Latin description. (3) Spinopilar jocheni spec. nov. is described from Barra de Guaratiba, Southeast RJ. It is characterized by the unarmed mesotergal areas. (4) Spinopilar martialis spec. nov. is described from Macaé, northern RJ. It is characterized by the pars stridens of the stridulatory organ on the pedipalpal femur, the unusual armature of scutal areas (2-2-10-10) and the extremely complex lobes of the stigmatic area in males, which connect the apophyses of coxa and trochanter IV. (5) Spinopilar magistralis spec. nov. is described from Búzios. It is characterized by extreme stoutness of leg IV and an elevated campaniform ocularium. A key is provided to 9 of the 10 species of Spinopilar and a new diagnosis is given for the genus. Two novel structures so far known only in Spinopilar are described: (1) a third type of pars stridens, which is different from the Tibangara-type and the Bissulla/Pseudopachylus-type both in topology and in structure of the ridges; (2) a proximal primary trochanteral cluster (PTC) composed of modified setae situated on the main apophysis of trochanter IV of males.
Two new species of Stenostygnus from South America (Opiliones: Biantidae: Stenostygninae)
Authors: MAMANI CLAUDIA VANESA , PORTO WILLIANS , IGLESIAS PATRICIA P. , PÉREZ-GONZÁLEZ ABEL
Published: June 2021

Stenostygnus martensi spec. nov. and Stenostygnus huberi spec. nov. are described from montane localities of the States of Mérida and Lara in Venezuela, and the diagnosis of the previously monotypic genus Stenostygnus Simon, 1879, is emended. The presence of these two new species as local endemics in Andean localities of Venezuela represents a huge range extension for the genus Stenostygnus, and the new localities are also ecologically different from previously known localities in the Amazon Basin. This could indicate the presence of a rich and uncharted diversity of stenostygnines in the Andean regions, particularly in the north of South America.
First record of Coillina baka Ying & Peng, 1998 (Araneae: Gnaphosidae) from Myanmar, with a description of the previously unknown female
Authors: SUZUKI YUYA , AUNG MU MU , ONO HIROTSUGU
Published: June 2021

The gnaphosid spider Coillina baka Yin & Peng, 1998, originally described from Yunnan, China is newly recorded from Chin State, Myanmar. While its holotype (male) was the only known record of the spider so far, the female is described and illustrated herein for the first time. The detailed structures of the male palp and female genitalia of this species are depicted, and its possible relationship with some species of Synaphosus Platnick & Shadab, 1980 is briefly discussed.
Preface
Authors: JÄGER PETER , SCHWENDINGER PETER , SHEAR WILLIAM A.
Published: June 2021

To process a Festschrift is an honour and a unique opportunity to show respect to someone who made important contributions over many years in a special field of scientific research. In the case of Jochen Martens the contribution is to not only in one field, but in several: harvestmen, birds, high mountains, taxonomy, systematics, evolution etc.
Eight legs, two wings, one life for scientific research—celebrating the 80th birthday of Prof. Dr Jochen Martens
Authors: JÄGER PETER , SCHÖNHOFER AXEL
Published: June 2021

The scientific life of Prof. Dr Jochen Martens (Germany: Mainz) is illuminated on occasion of his 80th birthday. Facts and impressions are given as well as lists of his publications (329), taxa he has described (2 families, 29 genera, 296 species) and that have been dedicated to him (11 genera, 219 species, 1 subspecies). Jochen Martens is a renowned specialist for birds (Aves) and for harvestmen (Opiliones). So far, he travelled to 27 countries in 80 journeys with Nepal and the Himalayas as one geographic focus.
Notes on coexistence of closely related Leiobunum rupestre and L. subalpinum (Opiliones, Eupnoi, Sclerosomatidae)
Authors: KOZEL PETER , DELAKORDA MIHA , KOMPOSCH CHRISTIAN , NOVAK LJUBA SLANA , NOVAK TONE , LIPOVŠEK SAŠKA
Published: June 2021

Two closely related, syntopic species, Leiobunum rupestre and L. subalpinum, spend the day at apparently randomly distributed resting sites. In this preliminary research, we studied differences in their microclimatic preferences at a locality in the Pohorje Mts., Slovenia. We measured air temperature and relative humidity at individual resting sites, and found that L. subalpinum occupied a slightly wider air temperature-relative humidity ecospace as compared to L. rupestre. Individuals of L. rupestre rested at more humid sites than L. subalpinum. Regression analyses revealed that the presence of L. rupestre was most likely at resting sites with air temperature in the range of 12–17°C and with relative air humidity of 98.1%. In contrast, the presence of L. subalpinum was most likely at resting sites with air temperature 23.1°C and relative air humidity in the range of 65–85%. Nevertheless, microclimatic niches of both species overlapped almost completely, indicating that niche filtering may allow the coexistence of the two species.
Expressions of Queer Intimacy: BDSM and Kink as Means of Self-Actualization
Authors: Muzacz Arien K.
Published: June 2021

Traditional concepts of sexuality and intimacy contain normative assumptions that limit the fluidity and creativity with which individuals’ relational, gender, and affectional identities can be expressed. This theoretical article applies the seven axioms of Hammack et al.’s paradigm of queer intimacy to a case study of a client who identifies as queer, kinky, poly, transmasculine, and neurodivergent. The resulting conceptualization illustrates ways in which kink and bondage/domination and sadomasochism can contribute to identity development, congruence, and self-actualization. Implications for counseling are provided along with humanistic themes found within the case study. Humanistic counselors can connect more authentically with queer, kinky, polyamorous clients by acknowledging the diversities of clients’ identities and behaviors and increasing counselor competencies related to queer, kink, and poly cultures and practices.
Numerical investigation of Miller cycle with EIVC and LIVC on a high compression ratio gasoline engine
Authors: Xu Jiangtao , Guo Tongjun , Feng Yong , Sun Mengxin
Published: June 2021

Previous studies have shown that increase compression ratio (CR) is an effective way to improve thermal efficiency of gasoline engine without changing the mechanical structure and working cycle, however, it is limited by engine knock when increasing the intake boosting under high load operation. This study aimed to solve the knock problem of gasoline engine with higher CR by application of Miller cycle, which can be implemented by either early or late intake valve closing (EIVC or LIVC). Therefore, in this paper, based on the engine with CR of 13.5 and electromagnetic valves train (EMVT), a comparative study was carried out to investigate the effects of EIVC and LIVC on engine performance, by theoretical modeling and calculation. The results show that, at high load, EIVC strategy is more preferred than LIVC owing to its lower total power consumption, which can improve the indicated mean effective pressure (IMEP) by 0.0371 bar, while enhance turbulence intensity and improve combustion. And at part load, the advantage for EIVC declines gradually, nevertheless, it can still sensitively adjust the EGR rate and thus reduce NOx. This results of quantitative analysis about two Miller cycles can provide valuable reference for engine designers and researchers.
The Impact of Screen-Free Zones in an Undergraduate Psychology Classroom: Assessing Exam Performance and Instructor Evaluations in Two Quasi-Experiments
Authors: Rhinehart Laura , Vazquez Salvador R. , Greenfield Patricia M.
Published: June 2021

Background:

With in-person instruction, many undergraduates look at screens during lectures. Because screens can distract, attempts to curb this behavior through screen policies are increasingly common but understudied.

Objective and Method:

Two quasi-experimental studies (Study 1: N = 412; Study 2: N = 179) in the same Psychology class explore results of restricting screens to one area of the classroom on exam performance and instructor/course evaluation.

Results:

In both studies, these policies improved exam scores in the class. In Study 2, students who chose to sit in the screen-free zone did better on exams. Limiting screen use to the back of the classroom (Study 1) produced student pushback in qualitative comments and lower evaluations in quantitative instructor and course ratings. In contrast, placing screen and screen-free zones side-by-side (Study 2) was accepted without comment by students.

Conclusion:

Together, these studies suggest that creating screen-free zones in classrooms can be beneficial for students, especially for those students who choose to sit in the screen-free section. Additionally, students accept side-by-side division of a classroom into screen and screen-free zones.

Teaching Implications:

Because these studies are ecologically valid, results have implications for how students take notes and how instructors set restrictions on screens in their classroom.
In a Class on Their Own: Investigating the Role of Social Integration in the Association Between Social Class and Mental Well-Being
Authors: Evans Olivia , Rubin Mark
Published: June 2021

It has been established that people from lower social classes tend to have poorer mental well-being compared with people from higher classes. Research also suggests that people from the lower classes are also less socially integrated. This research investigated the role of social integration in the relationship between social class and mental well-being across three studies (Study 1 N = 15,028; Study 2 N = 1,946; Study 3 N = 461). Across all studies, social class had an indirect effect on mental well-being via social integration. Moderation results found that social integration buffers the negative impact of financial issues on mental well-being, social support buffers the effects of class on mental ill-health, and family support amplifies rather than reduces social class differences in mental well-being. We propose that although improving social integration has the potential to improve the mental well-being of lower class populations, some caveats need to be considered.
Impacts of tailored, rehabilitation nursing care on functional ability and quality of life in hospitalized elderly patients after rib fractures
Authors: Granados Santiago María , Valenza Marie Carmen , Prados Román Esther , López López Laura , Muñoz Vigueras Natalia , Cabrera Martos Irene , Cebrià i Iranzo Maria Àngels
Published: June 2021

Objectives:

We aimed to analyze the effects of a tailored rehabilitation nursing care program on functional ability and quality of life in patients with conservative treatment for rib fractures.

Design:

Randomized controlled trial.

Setting:

Inpatient rehabilitation hospital.

Subjects:

Rib fracture patients treated conservatively were randomized into two groups (experimental and control group).

Interventions:

Patients in control group received Treatment as Usual (TAU) and patients included in experimental group received TAU and an added tailored rehabilitation nursing care program (RNT).

Main measures:

At baseline, and end of hospitalization treatment, the functional ability was assessed with the Barthel Index, and the quality of life was evaluated with the EuroQol-5D. Additionally, the outcomes were assessed at six-month follow-up.

Results:

A total of 80 patients were included in the study, whose mean age was 77.19 SD 7.71 in the RNT group and 75.55 SD 9.46 in the TAU group. Our data showed a significant difference in the post-treatment gains in overall quality of life (74.25 SD 20.62 vs 60.28 SD 20.54), and functional ability (71.79 SD 23.85 vs 69.41 SD 24.30) between the RNT group and the TAU group ( P < 0.05). Compared to the TAU group, the RNT group also showed a significant improvement in functional ability and quality of life at six-month follow-up.

Conclusions:

A tailored rehabilitation nursing care program added to the conservative treatment during hospitalization can improve the functional ability and quality of life of patients after rib fractures at discharge and at six-month follow-up.

Trial registration:

ClinicalTrial.gov Identifier: NCT04168996
Risks of Anaemia Among Pre-School Children Following Maternal Nutrition Education and Counselling in Urban Informal Settlements of Nairobi, Kenya
Authors: Nyamasege Carolyn Kemunto , Kimani-Murage Elizabeth W. , Imungi Jasper K. , Kaindi Dasel W. M. , Wagatsuma Yukiko
Published: June 2021

Slum environment may pose risk to child health and nutrition. This study assessed the risks of anemia among under five-year-old children, five years after implementing a nutrition education and counseling intervention in two urban slums in Nairobi, Kenya. A cross-sectional study was conducted in May 2018 as a follow-up of a randomized controlled study carried out between 2012–2015. A trained nurse measured hemoglobin levels of 438 children from households which participated in the initial study. Multivariate logistic regression was conducted to identify risks of anemia. The mean (+ SD) age of the children was 55.9 (5.3) months and mean (+ SD) hemoglobin was 10.7 (1.5) g/dL. Anemia prevalence was 59.8%, 33.9% had mild, 24.7% moderate, and 1.2% severe anemia. Absence of home toilet (AOR = 3.31; 95% CI, 1.20–9.09), household which paid to use a toilet facility (AOR = 1.86; 95% CI, 1.12–3.08), child’s frequency of eating colored fruits and vegetables (AOR = 0.28; 95% CI, 0.08–0.96), meat and meat products (AOR = 0.31; 95% CI, 0.23–6.01), number of meals a child aged <15years ate a day preceding the study (AOR = 1.49; 95% CI, 1.14–1.98), and a mother who had a history of anemia (AOR = 2.89; 95% CI, 1.22–12.01), were factors significantly associated with child’s anemia status. The environment of urban informal settings influences child anemia status. Further studies with interventions are therefore required in order to improve sanitation facilities and access to meats, fruits, and vegetables in urban slums through innovative kitchen gardens and small animal husbandry.
Margaret French Cresson at Chesterwood
Authors: Pilson Dana
Published: June 2021

Margaret French Cresson (1889‐1973) was the daughter of famed American sculptor Daniel Chester French (1850‐1931), who is well‐known for his Minute Man in Concord, Massachusetts, and his seated figure of Abraham Lincoln for the Lincoln Memorial in Washington, DC. Cresson was also a sculptor—she studied with her father, collaborated with him on works, and later became successful in the area of portraiture. Both father and daughter were active members of the National Sculpture Society, serving in leadership positions and contributing works to exhibitions. French and his family lived in New York City and spent their summers at Chesterwood, in Stockbridge, Massachusetts. Here, French built a modern studio and a comfortable residence, and he designed lush gardens and paths through the woods. After his death, Cresson inherited the site, and she worked to preserve her father's legacy by preserving his Studio, amassing a collection of his works, and creating a museum at Chesterwood, now a site of the National Trust for Historic Preservation. Many of her works are in the Chesterwood collection as well. To honor Cresson's preservation efforts and her talent as a sculptor, this season Chesterwood will exhibit some of her most successful portraits in the Studio. Next year, a full‐scale exhibition of her work will be presented throughout the site.
30-Day Outcomes for Total Ankle Arthroplasty in Patients With Anemia
Authors: Pollock Jordan R. , Doan Matt K. , Moore M. Lane , Hassebrock Jeffrey D. , Makovicka Justin L. , Deckey David G. , Kile Todd A. , Patel Karan A.
Published: June 2021

Background:

While anemia has been associated with poor surgical outcomes in total knee arthroplasty and total hip arthroplasty, the effects of anemia on total ankle arthroplasty remain unknown. This study examines how preoperative anemia affects postoperative outcomes in total ankle arthroplasty.

Methods:

A retrospective analysis was performed using the American College of Surgeons National Surgery Quality Improvement Project database from 2011 to 2018 for total ankle arthroplasty procedures. Hematocrit (HCT) levels were used to determine preoperative anemia.

Results:

Of the 1028 patients included in this study, 114 patients were found to be anemic. Univariate analysis demonstrated anemia was significantly associated with an increased average hospital length of stay (2.2 vs 1.8 days, P < .008), increased rate of 30-day readmission (3.5% vs 1.1%, P = .036), increased 30-day reoperation (2.6% vs 0.4%, P = .007), extended length of stay (64% vs 49.9%, P = .004), wound complication (1.75% vs 0.11%, P = .002), and surgical site infection (2.6% vs 0.6%, P = .017). Multivariate logistic regression analysis found anemia to be significantly associated with extended hospital length of stay (odds ratio [OR], 1.62; 95% CI, 1.07-2.45; P = .023) and increased reoperation rates (OR, 5.47; 95% CI, 1.15-26.00; P = .033). Anemia was not found to be a predictor of increased readmission rates (OR, 3.13; 95% CI, 0.93-10.56; P = .066) or postoperative complications (OR, 1.27; 95% CI, 0.35-4.56; P = .71).

Conclusion:

This study found increasing severity of anemia to be associated with extended hospital length of stay and increased reoperation rates. Providers and patients should be aware of the increased risks of total ankle arthroplasty with preoperative anemia.

Level of Evidence:

Level III, retrospective comparative study.
Using the capability approach in social work with unaccompanied young adult refugees
Authors: Van Raemdonck Laura , Clycq Noel , Mahieu Rilke
Published: June 2021

This study reviews two different types of frontline social services for unaccompanied young adult refugees participating in an intensive Social Support Programme implemented in 2016–2019 by a local municipality. More specifically, the study took a phenomenological research approach to review the impact of intensive case management and specialised educational/occupational orientation services on young refugees’ capabilities and agency to reach aspired life goals. The capability approach has been applied as a theoretical framework for identifying opportunities and challenges in this regard. The paper covers a mixed-method design that includes qualitative and quantitative data. The qualitative data are drawn from 42 in-depth interviews with 24 young refugees and one interview and three focus group discussions with 10 service providers. The article also includes a limited amount of longitudinal statistics on the aspirations of 31 young refugees upon entering and exiting the support programme.

Findings

This article shows theoretical and empirical evidence for utilising the capability approach to review social services for young refugees. Findings suggest that social workers and refugees face intersecting structural and interpersonal tensions that counteract with the expansion of young refugees’ capabilities and agency to reach their aspired life goals. Specific strategies are suggested to diminish described challenges.

Applications

Social work with unaccompanied young adult refugees should shift its attention from integrating these young individuals into the dominant social order, to prioritising their human development.
Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement
Authors: Liu Lumei , Dharmadhikari Sayali , Shontz Kimberly M , Tan Zheng Hong , Spector Barak M , Stephens Brooke , Bergman Maxwell , Manning Amy , Zhao Kai , Reynolds Susan D , Breuer Christopher K , Chiang Tendy
Published: June 2021

Decellularized tracheal scaffolds offer a potential solution for the repair of long-segment tracheal defects. However, complete decellularization of trachea is complicated by tracheal collapse. We created a partially decellularized tracheal scaffold (DTS) and characterized regeneration in a mouse model of tracheal transplantation. All cell populations except chondrocytes were eliminated from DTS. DTS maintained graft integrity as well as its predominant extracellular matrix (ECM) proteins. We then assessed the performance of DTS in vivo. Grafts formed a functional epithelium by study endpoint (28 days). While initial chondrocyte viability was low, this was found to improve in vivo. We then used atomic force microscopy to quantify micromechanical properties of DTS, demonstrating that orthotopic implantation and graft regeneration lead to the restoration of native tracheal rigidity. We conclude that DTS preserves the cartilage ECM, supports neo-epithelialization, endothelialization and chondrocyte viability, and can serve as a potential solution for long-segment tracheal defects.
Exploring microRNA target genes and identifying hub genes in bladder cancer based on bioinformatic analysis
Authors: Wu Hongjian , Jiang Wubing , Ji Guanghua , Xu Rong , Zhou Gaobo , Yu Hongyuan
Published: June 2021

Background

Bladder cancer (BC) is the second most frequent malignancy of the urinary system. The aim of this study was to identify key microRNAs (miRNAs) and hub genes associated with BC as well as analyse their targeted relationships.

Methods

According to the microRNA dataset GSE112264 and gene microarray dataset GSE52519, differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using the R limma software package. The FunRich software database was used to predict the miRNA-targeted genes. The overlapping common genes (OCGs) between miRNA-targeted genes and DEGs were screened to construct the PPI network. Then, gene ontology (GO) analysis was performed through the “cluster Profiler” and “org.Hs.eg.db” R packages. The differential expression analysis and hierarchical clustering of these hub genes were analysed through the GEPIA and UCSC Cancer Genomics Browser databases, respectively. KEGG pathway enrichment analyses of hub genes were performed through gene set enrichment analysis (GSEA).

Results

A total of 12 DEMs and 10 hub genes were identified. Differential expression analysis of the hub genes using the GEPIA database was consistent with the results for the UCSC Cancer Genomics Browser database. The results indicated that these hub genes were oncogenes, but VCL, TPM2, and TPM1 were tumour suppressor genes. The GSEA also showed that hub genes were most enriched in those pathways that were closely associated with tumour proliferation and apoptosis.

Conclusions

In this study, we built a miRNA-mRNA regulatory targeted network, which explores an understanding of the pathogenesis of cancer development and provides key evidence for novel targeted treatments for BC.
Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors
Authors: Wang Shuhang , Sun Jingwei , Chen Kun , Ma Peiwen , Lei Qi , Xing Shujun , Cao Zhongzheng , Sun Shujun , Yu Zicheng , Liu Yarong , Li Ning
Published: June 2021

Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to treat patients. Its diverse TCR clonality, superior tumor-homing ability, and low off-target toxicity endow TIL therapy unique advantages in treating solid tumors compared with other adoptive cellular therapies. Nevertheless, the successful application of TIL therapy currently is still limited to several types of tumors. Herein in this review, we summarize the fundamental work in the field of TIL therapy and the current landscape and advances of TIL clinical trials worldwide. Moreover, the limitations of the current TIL regimen have been discussed and the opportunities and challenges in the development of next-generation TIL are highlighted. Finally, the future directions of TIL therapy towards a broader clinical application have been proposed.
The regulation of miR-320a/XBP1 axis through LINC00963 for endoplasmic reticulum stress and autophagy in diffuse large B-cell lymphoma
Authors: Cui Yuying , Xu Hui , Yang Yu , Zhao Dongmei , Wen Yu , Lv Chao , Qiu Hongbin , Wang Chennan
Published: June 2021

Background

This study incorporates fundamental research referring to considerable amounts of gene-sequencing data and bioinformatics tools to analyze the pathological mechanisms of diffuse large B-cell lymphoma (DLBCL).

Methods

A lncRNA-miRNA-mRNA ceRNA network of DLBCL was constructed through database analysis combining GTEx and TCGA. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. After LINC00963 or miR-320a overexpression in vitro, western blot was performed to assess the protein levels of UPR sensors (GRP78, p-IRE1, IRE1, active ATF6, ATF4 and XBP1), along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62). Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay. 

Results

Following LINC00963 overexpression in vitro, SUDHL4 cell line showed a marked increase in the level of UPR-related GRP78, p-IRE1 and spliced XBP-1/XBP-1(s), apoptosis-related Bax and cleaved caspase 3, as well as autophagy-related Beclin1 and LC3II, whereas miR-320a mimic greatly diminished the effects of LINC00963 overexpression. Moreover, LINC00963 targeted miR-320a while miR-320a bound to the 3’UTR of XBP1. It was also found that LINC00963 overexpression resulted in significantly delayed tumor growth in a xenograft model of DLBCL. 

Conclusion

Mechanistically, LINC00963/miR-320a regulated XBP1-apoptosis pathway
and autophagy, implying the therapeutic potential of
this pathway for selective targeting. The data presented here illustrated
the mechanism of LINC00963/miR-320a/XBP1 in DLBCL for
the first time.
Bullatacin triggers immunogenic cell death of colon cancer cells by activating endoplasmic reticulum chaperones
Authors: Fan Fangtian , Shen Peiliang , Ma Yue , Ma Wangbo , Wu Hongyan , Liu Hao , An Qing
Published: June 2021

Background

It is well accepted that the immune system efficiently contributes to positive outcomes of chemotherapeutic cancer treatment by activating immunogenic cell death (ICD). However, only a limited number of ICD-inducing compounds are well characterized at present; therefore, identification of novel ICD inducers is urgently needed for cancer drug discovery, and the need is becoming increasingly urgent.

Methods

Herein, we assessed the antitumour activity of bullatacin by MTS assay and apoptosis assay. ICD biomarkers, such as calreticulin (CRT), high-mobility group protein B1 (HMGB-1), heat shock protein (HSP)70, HSP90 and ATP, were assessed by Western blotting, ELISA and flow cytometry. Western blot and qPCR assays were performed to explore the underlying mechanisms of bullatacin-induced ICD. Flow cytometry was used to detect macrophage phagocytosis.

Results

First, bullatacin induced apoptosis in both SW480 cells and HT-29 cells in a time-dependent manner at 10 nM, as assessed by flow cytometry. Moreover, Western blot and flow cytometry assays showed that CRT and HSP90 (biomarkers of early ICD) significantly accumulated on the cell membrane surface after approximately 6 h of treatment with bullatacin. In addition, ELISAs and Western blot assays showed that the second set of hallmarks required for ICD (HMGB1, HSP70 and HSP90) were released in the conditioned media of both SW480 and HT-29 cells after 36 h of treatment. Furthermore, qPCR and Western blot assays indicated that bullatacin triggered ICD via activation of the endoplasmic reticulum stress (ERS) signalling pathway. Finally, bullatacin promoted macrophage phagocytosis.

Conclusion

This study documents that bullatacin, a novel ICD inducer, triggers immunogenic tumour cell death by activating ERS even at a relatively low concentration in vitro.
The Bourque distances for mutation trees of cancers
Authors: Jahn Katharina , Beerenwinkel Niko , Zhang Louxin
Published: June 2021

Background

Mutation trees are rooted trees in which nodes are of arbitrary degree and labeled with a mutation set. These trees, also referred to as clonal trees, are used in computational oncology to represent the mutational history of tumours. Classical tree metrics such as the popular Robinson–Foulds distance are of limited use for the comparison of mutation trees. One reason is that mutation trees inferred with different methods or for different patients often contain different sets of mutation labels.

Results

We generalize the Robinson–Foulds distance into a set of distance metrics called Bourque distances for comparing mutation trees. We show the basic version of the Bourque distance for mutation trees can be computed in linear time. We also make a connection between the Robinson–Foulds distance and the nearest neighbor interchange distance.
European registry of type A aortic dissection (ERTAAD) - rationale, design and definition criteria
Authors: Biancari Fausto , Mariscalco Giovanni , Yusuff Hakeem , Tsang Geoffrey , Luthra Suvitesh , Onorati Francesco , Francica Alessandra , Rossetti Cecilia , Perrotti Andrea , Chocron Sidney , Fiore Antonio , Folliguet Thierry , Pettinari Matteo , Dell’Aquila Angelo M. , Demal Till , Conradi Lenard , Detter Christian , Pol Marek , Ivak Peter , Schlosser Filip , Forlani Stefano , Chetty Govind , Harky Amer , Kuduvalli Manoj , Field Mark , Vendramin Igor , Livi Ugolino , Rinaldi Mauro , Ferrante Luisa , Etz Christian , Noack Thilo , Mastrobuoni Stefano , De Kerchove Laurent , Jormalainen Mikko , Laga Steven , Meuris Bart , Schepens Marc , El Dean Zein , Vento Antti , Raivio Peter , Borger Michael , Juvonen Tatu
Published: June 2021

Background

Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient’s conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD.

Methods

Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient’s comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit.

Discussion

The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD.

Trial registration

ClinicalTrials.gov Identifier: NCT04831073.
Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations
Authors: Brouillard Pascal , Schlögel Matthieu J. , Homayun Sepehr Nassim , Helaers Raphaël , Queisser Angela , Fastré Elodie , Boutry Simon , Schmitz Sandra , Clapuyt Philippe , Hammer Frank , Dompmartin Anne , Weitz-Tuoretmaa Annamaria , Laranne Jussi , Pasquesoone Louise , Vilain Catheline , Boon Laurence M. , Vikkula Miikka
Published: June 2021

Background

Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients’ genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothelial cells (LECs) isolated from lesions. Our cohort (n = 143) was composed of unrelated patients suffering from a common lymphatic malformation (LM), a combined lymphatic malformation [lymphatico-venous malformation (LVM), capillaro-lymphatic malformation (CLM), capillaro-lymphatico-venous malformation (CLVM)], or a syndrome [CLVM with hypertrophy (Klippel-Trenaunay-Weber syndrome, KTS), congenital lipomatous overgrowth-vascular malformations-epidermal nevi -syndrome (CLOVES), unclassified PIK3CA-related overgrowth syndrome (PROS) or unclassified vascular (lymphatic) anomaly syndrome (UVA)].

Results

We identified a somatic PIK3CA mutation in resected lesions of 108 out of 143 patients (75.5%). The frequency of the variant allele ranged from 0.54 to 25.33% in tissues, and up to 47% in isolated endothelial cells. We detected a statistically significant difference in the distribution of mutations between patients with common and combined LM compared to the syndromes, but not with KTS. Moreover, the variant allele frequency was higher in the syndromes.

Conclusions

Most patients with an common or combined lymphatic malformation with or without overgrowth harbour a somatic PIK3CA mutation. However, in about a quarter of patients, no such mutation was detected, suggesting the existence of (an)other cause(s). We detected a hotspot mutation more frequently in common and combined LMs compared to syndromic cases (CLOVES and PROS). Diagnostic genotyping should thus not be limited to PIK3CA hotspot mutations. Moreover, the higher mutant allele frequency in syndromes suggests a wider distribution in patients’ tissues, facilitating detection. Clinical trials have demonstrated efficacy of Sirolimus and Alpelisib in treating patients with an LM or PROS. Genotyping might lead to an increase in efficacy, as treatments could be more targeted, and responses could vary depending on presence and type of PIK3CA-mutation.
Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients
Authors: Volbeda Meint , Jou-Valencia Daniela , van den Heuvel Marius C. , Knoester Marjolein , Zwiers Peter J. , Pillay Janesh , Berger Stefan P. , van der Voort Peter H. J. , Zijlstra Jan G. , van Meurs Matijs , Moser Jill
Published: June 2021

Background

The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury.

Methods

This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3–4 days for bacterial sepsis patients.

Results

We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42,p = 0.0002) and bacterial sepsis patients (fold change 0.24,p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3,p = 0.0006, PV-1 fold change 1.5,p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27,p < 0.0001) and bacterial sepsis patients (fold change 0.67,p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33,p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09,p < 0.0001) suggest decreased microvascular flow in COVID-19.

Conclusions

In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset.
An exploratory study of embitterment in traumatized refugees
Authors: Spaaij Julia , Schick Matthis , Bryant Richard A. , Schnyder Ulrich , Znoj Hansjörg , Nickerson Angela , Morina Naser
Published: June 2021

Background

Refugees and asylum seekers are frequently exposed to violence, human rights violations and unstable living conditions before, during, and after their displacement. Elevated prevalence rates of psychiatric disorders in forcibly displaced persons are well documented. However, less is known about other problems related to common refugee experiences, such as embitterment, moral injury, and diminished self-efficacy, and how they are related to trauma exposure and post-migration living difficulties.

Methods

A cross-sectional sample of 71 refugees and asylum seekers in treatment were examined regarding exposure to potentially traumatic events, post-migration living difficulties, moral injury appraisals, self-efficacy, and embitterment.

Results

Elevated levels of embitterment were reported by 68% of participants. The regression analysis revealed that greater moral injury appraisals and low levels of self-efficacy were significantly associated with higher levels of embitterment.

Conclusion

The results provide first insights into embitterment and associated factors in refugee populations. Furthermore, they highlight the significance of moral transgressions and low levels of self-efficacy emerging from displacement and traumatic experiences for the development of mental health problems in a clinical sample of refugees. The findings have implications for future research, policy development and clinical practice.
Relationship of psychosocial adversity to depressive symptoms and self-harm in young homeless people
Authors: Nambi Balamurugan , Majumder Pallab , Vostanis Panos
Published: June 2021

An increased incidence of psychiatric disorders has been reported in homeless young people. These disorders are often related to their childhood experience of trauma, although less is known about how secondary traumatic experiences while being homeless affect psychopathology. The aim of this study was to establish the relationship between life adversities – living on the street, physical and sexual abuse (during both childhood and young adult life) and substance misuse – and depressive symptoms and self-harm among homeless young people.
Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma
Authors: Michalski Jeff M. , Janss Anna J. , Vezina L. Gilbert , Smith Kyle S. , Billups Catherine A. , Burger Peter C. , Embry Leanne M. , Cullen Patricia L. , Hardy Kristina K. , Pomeroy Scott L. , Bass Johnnie K. , Perkins Stephanie M. , Merchant Thomas E. , Colte Paul D. , Fitzgerald Thomas J. , Booth Timothy N. , Cherlow Joel M. , Muraszko Karin M. , Hadley Jennifer , Kumar Rahul , Han Yuanyuan , Tarbell Nancy J. , Fouladi Maryam , Pollack Ian F. , Packer Roger J. , Li Yimei , Gajjar Amar , Northcott Paul A.
Published: June 2021

PURPOSE

Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense of adverse consequences of treatment. Efforts to mitigate these effects include deintensification of craniospinal irradiation (CSI) dose and volume.

METHODS

ACNS0331 (ClinicalTrials.gov identifier: NCT00085735 ) randomly assigned patients age 3-21 years with average-risk MB to receive posterior fossa radiation therapy (PFRT) or involved field radiation therapy (IFRT) following CSI. Young children (3-7 years) were also randomly assigned to receive standard-dose CSI (SDCSI; 23.4 Gy) or low-dose CSI (LDCSI; 18 Gy). Post hoc molecular classification and mutational analysis contextualized outcomes according to known biologic subgroups (Wingless, Sonic Hedgehog, group 3, and group 4) and genetic biomarkers. Neurocognitive changes and ototoxicity were monitored over time.

RESULTS

Five hundred forty-nine patients were enrolled on study, of which 464 were eligible and evaluable to compare PFRT versus IFRT and 226 for SDCSI versus LDCSI. The five-year event-free survival (EFS) was 82.5% (95% CI, 77.2 to 87.8) and 80.5% (95% CI, 75.2 to 85.8) for the IFRT and PFRT regimens, respectively, and 71.4% (95% CI, 62.8 to 80) and 82.9% (95% CI, 75.6 to 90.2) for the LDCSI and SDCSI regimens, respectively. IFRT was not inferior to PFRT (hazard ratio, 0.97; 94% upper CI, 1.32). LDCSI was inferior to SDCSI (hazard ratio, 1.67%; 80% upper CI, 2.10). Improved EFS was observed in patients with Sonic Hedgehog MB who were randomly assigned to the IFRT arm ( P = .018). Patients with group 4 MB receiving LDCSI exhibited inferior EFS ( P = .047). Children receiving SDCSI exhibited greater late declines in IQ (estimate = 5.87; P = .021).

CONCLUSION

Reducing the radiation boost volume in average-risk MB is safe and does not compromise survival. Reducing CSI dose in young children with average-risk MB results in inferior outcomes, possibly in a subgroup-dependent manner, but is associated with better neurocognitive outcome. Molecularly informed patient selection warrants further exploration for children with MB to be considered for late-effect sparing approaches.
Scaling of oscillatory kinematics and Froude efficiency in baleen whales
Authors: Gough William T. , Smith Hayden J. , Savoca Matthew S. , Czapanskiy Max F. , Fish Frank E. , Potvin Jean , Bierlich K. C. , Cade David E. , Di Clemente Jacopo , Kennedy John , Segre Paolo , Stanworth Andrew , Weir Caroline , Goldbogen Jeremy A.
Published: June 2021

High efficiency lunate-tail swimming with high-aspect-ratio lifting surfaces has evolved in many vertebrate lineages, from fish to cetaceans. Baleen whales (Mysticeti) are the largest swimming animals that exhibit this locomotor strategy, and present an ideal study system to examine how morphology and the kinematics of swimming scale to the largest body sizes. We used data from whale-borne inertial sensors coupled with morphometric measurements from aerial drones to calculate the hydrodynamic performance of oscillatory swimming in six baleen whale species ranging in body length from 5 to 25 m (fin whale, Balaenoptera physalus; Bryde's whale, Balaenoptera edeni; sei whale, Balaenoptera borealis; Antarctic minke whale, Balaenoptera bonaerensis; humpback whale, Megaptera novaeangliae; and blue whale, Balaenoptera musculus). We found that mass-specific thrust increased with both swimming speed and body size. Froude efficiency, defined as the ratio of useful power output to the rate of energy input ( Sloop, 1978), generally increased with swimming speed but decreased on average with increasing body size. This finding is contrary to previous results in smaller animals, where Froude efficiency increased with body size. Although our empirically parameterized estimates for swimming baleen whale drag were higher than those of a simple gliding model, oscillatory locomotion at this scale exhibits generally high Froude efficiency as in other adept swimmers. Our results quantify the fine-scale kinematics and estimate the hydrodynamics of routine and energetically expensive swimming modes at the largest scale.
Evaluation of a personal professional mentor scheme for newly qualified nurses
Authors: Austin Charlotte , Halpin Yvonne
Published: June 2021

Background:

Newly qualified nurses are known to experience a range of feelings and fears in the first transitional 12 months post-qualifying, with absence and turnover among potential outcomes.

Aim:

To evaluate the personal professional mentor role and scheme, a new pastoral support initiative, from the perspective of participating newly qualified nurses.

Methods:

Newly qualified paediatric nurses (n=10), who had been assigned a personal professional mentor (an experienced nurse who worked elsewhere in their employing NHS Trust), completed a semi-structured interview. The data were analysed using thematic analysis.

Findings:

The personal professional mentor counteracted some aspects of transition isolation for the newly qualified nurses. They were an independent, accessible, experienced confidant and a welcome new supportive role.

Conclusion:

Pairing experienced nurses with newly qualified nurses provided a new type of workplace support during transition. Inexpensive to set up and run, it is an easy addition to any portfolio of support strategies.