bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing of URM wall-to-diaphragm through-bolt plate anchor connections
Authors: Dizhur Dmytro , Wei Shou , Giaretton Marta , Schultz Arturo E. , Ingham Jason M. , Giongo Ivan
Published: August 2020

The presence of effective wall-to-diaphragm connections has been shown to significantly improve the global seismic behavior of unreinforced masonry (URM) buildings. However, despite the importance of such connections, there remains a paucity of experimental research to provide physical validation of current recommendations in design standards and guidelines. The experimental study reported herein included a total of 18 tests which were undertaken in two phases, with Phase 1 testing being undertaken on existing vintage plate anchor connections in an existing URM building and Phase 2 testing involving newly installed plate anchor connections in two additional existing URM buildings. The tested buildings offered variation in material properties, levels of axial load, and wall thickness as test parameters. Attained failure modes and corresponding force-displacement curves are presented herein, as well as comparisons regarding the influence of varying test parameters on the ultimate pull-out capacity. Prediction of plate anchor capacity was undertaken using a basic mechanics approach, and comparisons to current strength recommendations in standards and guidelines are provided.
FcγRIIA expression accelerates nephritis and increases platelet activation in systemic lupus erythematosus
Authors: Melki Imene , Allaeys Isabelle , Tessandier Nicolas , Mailhot Benoit , Cloutier Nathalie , Campbell Robert A. , Rowley Jesse W. , Salem David , Zufferey Anne , Laroche Audrée , Lévesque Tania , Patey Natalie , Rauch Joyce , Lood Christian , Droit Arnaud , McKenzie Steven E. , Machlus Kellie R. , Rondina Matthew T. , Lacroix Steve , Fortin Paul R. , Boilard Eric
Published: August 2020

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by deposits of immune complexes (ICs) in organs and tissues. The expression of FcγRIIA by human platelets, which is their unique receptor for immunoglobulin G antibodies, positions them to ideally respond to circulating ICs. Whereas chronic platelet activation and thrombosis are well-recognized features of human SLE, the exact mechanisms underlying platelet activation in SLE remain unknown. Here, we evaluated the involvement of FcγRIIA in the course of SLE and platelet activation. In patients with SLE, levels of ICs are associated with platelet activation. Because FcγRIIA is absent in mice, and murine platelets do not respond to ICs in any existing mouse model of SLE, we introduced the FcγRIIA (FCGR2A) transgene into the NZB/NZWF1 mouse model of SLE. In mice, FcγRIIA expression by bone marrow cells severely aggravated lupus nephritis and accelerated death. Lupus onset initiated major changes to the platelet transcriptome, both in FcγRIIA-expressing and nonexpressing mice, but enrichment for type I interferon response gene changes was specifically observed in the FcγRIIA mice. Moreover, circulating platelets were degranulated and were found to interact with neutrophils in FcγRIIA-expressing lupus mice. FcγRIIA expression in lupus mice also led to thrombosis in lungs and kidneys. The model recapitulates hallmarks of human SLE and can be used to identify contributions of different cellular lineages in the manifestations of SLE. The study further reveals a role for FcγRIIA in nephritis and in platelet activation in SLE.
Mechanistic insights and potential therapeutic approaches forNUP98-rearranged hematologic malignancies
Authors: Michmerhuizen Nicole L. , Klco Jeffery M. , Mullighan Charles G.
Published: August 2020

Nucleoporin 98 (NUP98) fusion oncoproteins are observed in a spectrum of hematologic malignancies, particularly pediatric leukemias with poor patient outcomes. Although wild-type full-length NUP98 is a member of the nuclear pore complex, the chromosomal translocations leading to NUP98 gene fusions involve the intrinsically disordered and N-terminal region of NUP98 with over 30 partner genes. Fusion partners include several genes bearing homeodomains or having known roles in transcriptional or epigenetic regulation. Based on data in both experimental models and patient samples, NUP98 fusion oncoprotein–driven leukemogenesis is mediated by changes in chromatin structure and gene expression. Multiple cofactors associate with NUP98 fusion oncoproteins to mediate transcriptional changes possibly via phase separation, in a manner likely dependent on the fusion partner. NUP98 gene fusions co-occur with a set of additional mutations, including FLT3–internal tandem duplication and other events contributing to increased proliferation. To improve the currently dire outcomes for patients with NUP98-rearranged malignancies, therapeutic strategies have been considered that target transcriptional and epigenetic machinery, cooperating alterations, and signaling or cell-cycle pathways. With the development of more faithful experimental systems and continued study, we anticipate great strides in our understanding of the molecular mechanisms and therapeutic vulnerabilities at play in NUP98-rearranged models. Taken together, these studies should lead to improved clinical outcomes for NUP98-rearranged leukemia.
Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma: an open-label phase 2 study
Authors: Kim Seok Jin , Lim Jing Quan , Laurensia Yurike , Cho Junhun , Yoon Sang Eun , Lee Ji Young , Ryu Kyung Ju , Ko Young Hyeh , Koh Youngil , Cho Duck , Lim Soon Thye , Enemark Marie Beck , D’Amore Francesco , Bjerre Mette , Ong Choon Kiat , Kim Won Seog
Published: August 2020

This study aimed to assess the efficacy and safety of treatment with avelumab, an anti–programmed death ligand 1 (PD-L1) antibody, in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (ENKTL). In this phase 2 trial, 21 patients with relapsed or refractory ENKTL were treated with 10 mg/kg of avelumab on days 1 and 15 of a 28-day cycle. The primary end point was the complete response (CR) rate based on the best response. Targeted sequencing and immunohistochemistry were performed using pretreatment tumor tissue, and blood samples were drawn before and after treatment for measurement of cytokines and soluble programmed cell death protein 1 (PD1), PD-L1, and PD-L2. The CR rate was 24% (5 of 21), and the overall response rate was 38% (8 of 21). Although nonresponders showed early progression, 5 responders currently continue to receive treatment and have maintained their response. Most treatment-related adverse events were grade 1 or 2; no grade 4 adverse events were observed. Treatment responses did not correlate with mutation profiles, tumor mutation burden, serum levels of cytokines, or soluble PD1/PD-L1 and PD-L2. However, the response to avelumab was significantly associated with the expression of PD-L1 by tumor tissue (P = .001). Therefore, all patients achieving CR showed high PD-L1 expression, and their tumor subtyping based on PD-L1 expression correlated with treatment response. In summary, avelumab showed single-agent activity in a subset of patients with relapsed or refractory ENKTL. The assessment of PD-L1 expression on tumor cells might be helpful for identifying responders to avelumab. This trial was registered at www.clinicaltrials.gov as #NCT03439501.
Transcriptional variation of sensory-related genes in natural populations of Aedes albopictus
Authors: Gomulski Ludvik M. , Manni Mosè , Carraretto Davide , Nolan Tony , Lawson Daniel , Ribeiro José M. , Malacrida Anna R. , Gasperi Giuliano
Published: August 2020

Background

The Asian tiger mosquito,Aedes albopictus, is a highly dangerous invasive vector of numerous medically important arboviruses including dengue, chikungunya and Zika. In four decades it has spread from tropical Southeast Asia to many parts of the world in both tropical and temperate climes. The rapid invasion process of this mosquito is supported by its high ecological and genetic plasticity across different life history traits. Our aim was to investigate whether wild populations, both native and adventive, also display transcriptional genetic variability for functions that may impact their biology, behaviour and ability to transmit arboviruses, such as sensory perception.

Results

Antennal transcriptome data were derived from mosquitoes from a native population from Ban Rai, Thailand and from three adventive Mediterranean populations: Athens, Greece and Arco and Trento from Italy. Clear inter-population differential transcriptional activity was observed in different gene categories related to sound perception, olfaction and viral infection. The greatest differences were detected between the native Thai and the Mediterranean populations. The two Italian populations were the most similar.

Nearly one million quality filtered SNP loci were identified.

Conclusion

The ability to express this great inter-population transcriptional variability highlights, at the functional level, the remarkable genetic flexibility of this mosquito species. We can hypothesize that the differential expression of genes, including those involved in sensory perception, in different populations may enableAe. albopictusto exploit different environments and hosts, thus contributing to its status as a global vector of arboviruses of public health importance.

The large number of SNP loci present in these transcripts represents a useful addition to the arsenal of high-resolution molecular markers and a resource that can be used to detect selective pressure and adaptive changes that may have occurred during the colonization process.
Tertiary lymphoid structure related B-cell IgE isotype switching and secondary lymphoid organ linked IgE production in mouse allergy model
Authors: Chudakov Dmitrii Borisovich , Ryasantsev Dmitrii Yuryevich , Tsaregorotseva Daria Sergeevna , Kotsareva Olga Dmitrievna , Fattakhova Gulnar Vaisovna , Svirshchevskaya Elena Viktorovna
Published: August 2020

Background

Numerous data obtained by different research laboratories indicate that specific IgE production is triggered independently of specific IgG or IgA ones and so it is not linked to fully matured germinal centers formation in the secondary lymphoid organs. The aim of this study was to clarify whether specific IgE production is triggered by low antigen doses administrated in tertiary tissues enriched by lymphoid structures.

Methods

Ovalbumin (OVA) in different doses (100 ng to 10 μg) was administrated three times a week for 4–5 weeks intraperitoneally (i.p.) or subcutaneously (s.c.) to female BALB/c mice in the wither region which is enriched in fat-associated lymphoid clusters or in the foot pad region not containing them.

Results

OVA-specific IgE was predominantly induced by low but not high antigen doses and only after immunization into the withers. IgE isotype switching was triggered exclusively in the withers adipose tissue but not in the regional lymph nodes while mature IgE expressing cells were observed both in the withers and lymph nodes. Anti-proliferative genotoxic stress inducing drugs shifted the balance from IgG1 towards IgE production.

Conclusions

Tertiary lymphoid structures possess unique environment where B-cell antibody isotype switching to IgE predominantly occurs. This phenomenon is partially explained by hampered proliferation of B-cells in these structures.
Effects of hyperthermia on the effective concentration of rocuronium and sugammadex-mediated reversal in isolated phrenic nerve hemidiaphragm preparations of rats
Authors: Kim Jin Sun , Kim Young Mu , Kim Ha Jung , Choi Jae Moon , Kim Yong Beom , Song Jae Seok , Yang Hong Seuk
Published: August 2020

Background

Hyperthermia is relatively rare during general anesthesia; however, a few studies have been conducted on hyperthermia and the neuromuscular blockade (NMB) induced by rocuronium, and the reversal of NMB by sugammadex. We investigated the effect of hyperthermia status on the NMB induced by rocuronium, and its reversal by sugammadex, in isolated phrenic nerve hemidiaphragm (PNHD) preparations of the rat.

Methods

Thirty-three male Sprague-Dawley rat PNHD preparations were randomly assigned to three groups at different temperatures (36 °C, 38 °C, and 40 °C; each group, n = 11, in Krebs solution). The train-of-four (TOF) and twitch height responses were checked mechanomyographically. The PNHD were treated with progressively increasing doses of rocuronium and three effective concentrations (ECs), EC50, EC90, and EC95, of rocuronium were analyzed in each group via nonlinear regression analysis. Then, sugammadex was administered in doses equimolar to rocuronium. Thereafter, the T1 height (%), TOFR (%) and the duration index were measured.

Results

The EC of rocuronium (EC50, EC90, and EC95) decreased significantly in accordance with increasing temperature. The groups at 36 °C and 40 °C showed clear differences in all areas (all P < 0.001). Moreover, the T1 height (%) and the duration index upon sugammadex administration showed faster recovery results in the36 °C than the 38 °C and 40 °C groups.

Conclusion

A rise of temperature from 38 °C to 40 °C in rat PNHD preparations proportionally enhanced the NMB induced by rocuronium. In addition, equimolar doses of sugammadex to the administered rocuronium showed a slower recovery time as the temperature rises.
Findings in whole body MRI and conventional imaging in patients with fever of unknown origin-a retrospective study
Authors: Tavakoli Anoshirwan Andrej , Reichert Miriam , Blank Tanja , Dinter Dietmar , Weckbach Sabine , Buchheidt Dieter , Schoenberg Stefan Oswald , Attenberger Ulrike
Published: August 2020

Background

To analyse the influence of whole body (wb)-MRI on patient management compared to routine diagnostic tests in patients with fever of unknown origin (FUO).

Methods

Twenty-four patients with FUO, defined as illness of more than three weeks with fever greater than 38.3 °C, underwent wb-MRI at a 1.5 T MR-system. The MR-protocol consisted of the following sequences: axial T1 VIBE, coronal T2-TIRM and a coronal echoplanar diffusion weighted sequence (overall acquisition time 29:39 min:s). Furthermore, laboratory findings, chest-x-ray, abdominal ultrasound, CT-scans and/or PET-CT scans were evaluated and compared to the wb-MRI findings in regard to treatment changes.

Results

Wb-MRI yielded a correct diagnosis in 70% of the patients. In 46% the inflammatory focus was exclusively detected by wb-MRI. Focus detection by wb-MRI led to a subsequent change of the clinical management in 92% of the patients. In 6 patients both a wb-MRI and a PET-CT were performed yielding the correct diagnosis in the same 4 of 6 patients for both imaging modalities.

Conclusions

Wb-MRI appears to be of value in the evaluation of FUO patients, allowing for optimized treatment by increasing diagnostic certainty. Due to its lack of nephrotoxicity and ionizing radiation it may be preferred over standard imaging techniques and PET-CT in the future. However, given the low number of patients in our trial, further prospective studies have to be performed to confirm our results.
Intraoperative cell salvage for obstetrics: a prospective randomized controlled clinical trial
Authors: Liu Ye , Li Xiaoguang , Che Xiangming , Zhao Guosheng , Xu Mingjun
Published: August 2020

Background

The latest basic studies and clinical evidence have confirmed the safety and efficacy of intraoperative autologous blood cell transfusion in cardiac surgery and orthopaedics. However, in caesarean section, there are still concerns about the contamination of amniotic fluid and foetal components, and consequently the application of intraoperative autologous blood cell transfusion is not universal. Therefore, this study aimed to evaluate the clinical value of intraoperative autologous blood cell transfusion in obstetric surgery.

Methods

A prospective, randomized, controlled, feasibility study was performed in women undergoing caesarean section. One hundred sixteen participants were randomly assigned at a 1:1 ratio into either the intraoperative cell salvage group or the control group. Allogeneic blood cells were transfused into patients with haemoglobin concentrations < 80 g/dL in both the intraoperative cell salvage group and the control group.

Results

No significant differences were found between the two groups in age, weight, maternal parity, history of previous caesarean section, gestational weeks of delivery, etc. However, compared with the control group, patients in the intraoperative cell salvage group had a significantly lower amount of allogeneic blood cell transfusion, lower incidence of postoperative incision infection, delayed wound healing, perioperative allergy, adverse cardiovascular events, hypoproteinaemia and shorter hospital stay.

Conclusion

The results of this study suggest that the use of autologous blood cell transfusion is safe and effective for patients with obstetric haemorrhage. Trial registration: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (2016-XJS-003-01) as well as the 1964 Helsinki Declaration and its later amendments or other comparable ethical standards. The clinical trials were registered (ChiCTR-ICC-15,007,096) on September 28, 2015.
A single-center, randomized, non-inferiority study evaluating seroma formation after mastectomy combined with flap fixation with or without suction drainage: protocol for the Seroma reduction and drAin fRee mAstectomy (SARA) trial
Authors: de Rooij Lisa , van Kuijk Sander M. J. , van Haaren Els R. M. , Janssen Alfred , Vissers Yvonne L. J. , Beets Geerard L. , van Bastelaar James
Published: August 2020

Background

Seroma formation is a common complication after breast cancer surgery and can lead to delayed wound healing, infection, patient discomfort and repeated visits to the outpatient clinic. Mastectomy combined with flap fixation is becoming standard practice and is currently combined with closed-suction drainage. There is evidence showing that closed-suction drainage may be insufficient in preventing seroma formation. There is reasonable doubt whether there is still place for closed-suction drainage after mastectomy when flap fixation is performed.

We hypothesize that mastectomy combined with flap fixation and closed suction drainage does not cause a significant lower incidence of seroma aspirations, when compared to mastectomy and flap fixation alone. Furthermore, we expect that patients without drainage will experience significantly less discomfort and comparable rates of surgical site infections.

Methods

This is a randomized controlled trial in female breast cancer patients undergoing mastectomy and flap fixation using sutures with or without sentinel lymph node biopsy (SLNB). Patients will be eligible for inclusion if they are older than 18 years, have an indication for mastectomy with or without sentinel procedure. Exclusion criteria are modified radical mastectomy, direct breast reconstruction, previous history of radiation therapy of the unilateral breast, breast conserving therapy and inability to give informed consent. A total of 250 patients will be randomly allocated to one of two groups: mastectomy combined with flap fixation and closed-suction drainage or mastectomy combined with flap fixation without drainage. Follow-up will be conducted up to six months postoperatively. The primary outcome is the proportion of patients undergoing one or more seroma aspirations. Secondary outcome measures consist of the number of invasive interventions, surgical site infection, quality of life measured using the SF-12 Health Survey, cosmesis, pain and number of additional outpatient department visits.

Discussion

To our knowledge, no randomized controlled trial has been conducted comparing flap fixation with and without closed-suction drainage with seroma aspiration as the primary outcome. This study could result in finding evidence that supports performing mastectomy without closed-suction drainage.

Trial registration

This trial was approved by the medical ethical committee of Zuyderland Medical Center METC-Z on 20 March 2019 (METCZ20190023). The SARA Trial was registered atClinicalTrials.govas per July 2019, Identifier:NCT04035590.
Colostrum oropharyngeal immunotherapy for very low birth weight preterm infants: protocol of an intervention study
Authors: da Cruz Martins Camilla , de Santana Xavier Ramos Michelle , Viana Cardoso Amaral Mara , Santos Passos Costa Jéssica , Souza Cerqueira Ellayne , de Oliveira Vieira Tatiana , dA Cruz Simone Seixas , Oliveira Vieira Graciete
Published: August 2020

Background

The oropharyngeal colostrum administration protocol to treat premature newborns is a possible and plausible strategy in neonatal health services, since the immunoprotective components of colostrum can be absorbed by the lymphoid tissues of the oropharynx. In this context, this study aims to describe the implementation of oropharyngeal colostrum immunotherapy in very low birth weight preterm newborns in a neonatal unit, as well as to test an algorithm in a public hospital.

Methods

The protocol is applied in a non-randomized, superiority clinical trial with historical control. In the treatment group, 0.2 mL of raw colostrum is dripped into the right and left oropharyngeal mucosa, totaling 8 administrations every 24 h until the 7th complete day of life interruptedly. The control group consists of very low birth weight preterm newborns born in the same hospital in previous years (historical control). The clinical progression of 60 newborns until hospital discharge is recorded on standardized forms. A total of 350 participants are estimated to complete the survey in 4 years. The occurrence of continuous outcomes between the groups are compared through the paired t-test or Wilcoxon’s two-sample test. The chi-square test or Fisher’s exact test, and survival analysis are used for binary outcomes. The nutritional status is assessed through Intergrowth-21st growth curves for preterm newborns.

Discussion

The flows of the protocol’s actions is sorted by an algorithm, compatible with the Brazilian reality of a public hospital. This measure facilitates and systematizes clinical care, organizes the team’s work process, speeds up the intervention steps, standardizes decision-making and unifies the quality of care, besides showing the feasibility of oropharyngeal colostrum immunotherapy.

Trial registration

ReBEC,U1111–1222-0598, Registered 09 October 2018,http://www.ensaiosclinicos.gov.br/rg/RBR-2cyp7c/.
Exploring the costs, consequences and efficiency of three types of palliative care day services in the UK: a pragmatic before-and-after descriptive cohort study
Authors: Mitchell Paul Mark , Coast Joanna , Myring Gareth , Ricciardi Federico , Vickerstaff Victoria , Jones Louise , Zafar Shazia , Cudmore Sarah , Jordan Joanne , McKibben Laurie , Graham-Wisener Lisa , Finucane Anne M. , Hewison Alistair , Haraldsdottir Erna , Brazil Kevin , Kernohan W. George
Published: August 2020

Background

Palliative Care Day Services (PCDS) offer supportive care to people with advanced, progressive illness who may be approaching the end of life. Despite the growth of PCDS in recent years, evidence of their costs and effects is scarce. It is important to establish the value of such services so that health and care decision-makers can make evidence-based resource allocation decisions. This study examines and estimates the costs and effects of PCDS with different service configurations in three centres across the UK in England, Scotland and Northern Ireland.

Methods

People who had been referred to PCDS were recruited between June 2017 and September 2018. A pragmatic before-and-after descriptive cohort study design analysed data on costs and outcomes. Data on costs were collected on health and care use in the 4 weeks preceding PCDS attendance using adapted versions of the Client Service Receipt Inventory (CSRI). Outcomes, cost per attendee/day and volunteer contribution to PCDS were also estimated. Outcomes included quality of life (MQOL-E), health status (EQ-5D-5L) and capability wellbeing (ICECAP-SCM).

Results

Thirty-eight attendees were recruited and provided data at baseline and 4 weeks (centre 1:n = 8; centre 2:n = 8, centre 3:n = 22). The cost per attendee/day ranged from £121–£190 (excluding volunteer contribution) to £172–£264 (including volunteer contribution) across the three sites. Volunteering constituted between 28 and 38% of the total cost of PCDS provision. There was no significant mean change at 4 week follow-up from baseline for health and care costs (centre 1: £570, centre 2: -£1127, centre 3: £65), or outcomes: MQOL-E (centre 1: − 0.48, centre 2: 0.01, centre 3: 0.24); EQ-5D-5L (centre 1: 0.05, centre 2: 0.03, centre 3: − 0.03) and ICECAP-SCM (centre 1:0.00, centre 2: − 0.01, centre 3: 0.03). Centre costs variation is almost double per attendee when attendance rates are held constant in scenario analysis.

Conclusions

This study highlights the contribution made by volunteers to PCDS provision. There is insufficient evidence on whether outcomes improved, or costs were reduced, in the three different service configurations for PCDS. We suggest how future research may overcome some of the challenges we encountered, to better address questions of cost-effectiveness in PCDS.
What are the needs of people with dementia in acute hospital settings, and what interventions are made to meet these needs? A systematic integrative review of the literature
Authors: Røsvik Janne , Rokstad Anne Marie Mork
Published: August 2020

Background

Research aiming to improve the hospital experience for patients with dementia and their informal carers is strongly recommended. The present review aimed to describe the research on interventions to meet the needs of people with dementia in acute hospital settings regarding physical environment, organization of care, and staff knowledge of dementia and competence in person-centred care. An integrative review design was applied. We searched for studies in PubMed, Ovid Medline, Cinahl, Embase, Swemed+, and Cochrane databases using the Mixed Methods Appraisal Tool (MMAT) for quality evaluation. Twenty-seven articles were included, describing the perspectives of people with dementia, informal carers, and professional carers. The MMAT score ranged from two to four. Twelve studies described needs and experiences, mostly using a qualitative design. Common themes and results were synthesized. The studies identified a need to enhance staff competence regarding dementia and person-centred care. Fifteen studies described interventions: two were qualitative; three used mixed method, and 10 were quantitative, of which two were randomized controlled trials and eight were observational studies. Five types of interventions were identified. Three types could positively impact staff knowledge about dementia and person-centred care. One type was experienced as positive regarding organisation of care for patients with dementia. None of the intervention studies found evidence for effects on the identified needs regarding physical environment.

Conclusion

The included studies suggest that staff need more knowledge regarding dementia and person-centred dementia care and that training interventions implemented to enhance staff competence had promising results. However, there is a need for research on the needs of patients with dementia in acute hospital settings regarding physical environment and effect of design elements. There is also a scarcity of intervention studies focusing on the effect of models of care that support the psychosocial needs of patients with dementia.
Long non-coding RNA SNHG6 regulates the sensitivity of prostate cancer cells to paclitaxel by sponging miR-186
Authors: Cao Chunhui , Sun Guanghai , Liu Chunlin
Published: August 2020

Background

Chemo-resistance is one of the main obstacles in the treatment of prostate cancer (PCa). Long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) is involved in the chemo-resistance of various tumors. We aim to survey the role and underlying molecular mechanism of SNHG6 in PCa resistance to paclitaxel (PTX).

Methods

The expression of SNHG6 and miR-186 was detected using quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, and apoptosis of PTX-resistant PCa cells were determined via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), transwell assay, or flow cytometry assay. Protein levels of CyclinD1, matrix metalloproteinase 9 (MMP9), Vimentin, E-cadherin, Cleaved-caspase-3 (Cleaved-casp-3) Cleaved-caspase-9 (Cleaved-casp-9), Multidrug Resistance associated Protein 1 (MRP1), and multidrug resistance-1 (MDR1) were assessed by western blot analysis. The relationship between SNHG6 and miR-186 were confirmed by dual-luciferase reporter assay. The role of SNHG6 in vivo was confirmed by xenograft tumor model.

Results

SNHG6 expression was increased and miR-186 expression was reduced in drug-resistant PCa tissues and cells. SNHG6 knockdown elevated PTX-resistant PCa cells sensitivity to PTX in vitro and in vivo, and repressed proliferation, migration, and invasion of PTX-resistant PCa cells in vitro. Importantly, SNHG6 acted as a sponge of miR-186. Furthermore, miR-186 downregulation reversed SNHG6 silencing-mediated cell sensitivity to PTX, proliferation, migration, and invasion in PTX-resistant PCa cells.

Conclusions

SNHG6 knockdown elevated the sensitivity of PTX-resistant PCa cells to PTX by sponging miR-186, indicating that SNHG6 might be a therapeutic target for PCa.
Novel insights into the interplay between m6A modification and noncoding RNAs in cancer
Authors: Yi You-Cai , Chen Xiao-Yu , Zhang Jing , Zhu Jin-Shui
Published: August 2020

N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotes, mainly in messenger RNA (mRNA). Increasing evidence shows that m6A methylation modification acts an essential role in various physiological and pathological bioprocesses. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs and circRNAs, are known to participate in regulating cell differentiation, angiogenesis, immune response, inflammatory response and carcinogenesis. m6A regulators, such as METTL3, ALKBH5 and IGF2BP1 have been reported to execute a m6A-dependent modification of ncRNAs involved in carcinogenesis. Meanwhile, ncRNAs can target or modulate m6A regulators to influence cancer development. In this review, we provide an insight into the interplay between m6A modification and ncRNAs in cancer.
Prognostic prediction of systemic immune-inflammation index for patients with gynecological and breast cancers: a meta-analysis
Authors: Ji Yongfang , Wang Haiyan
Published: August 2020

Background

Systemic immune-inflammation index (SII) has been suggested to be effective to reflect the inflammatory status and thus may be an underlying biomarker for prognosis prediction. This hypothesis has been demonstrated in meta-analyses on several cancer types. However, there was no study to confirm the prognostic roles of SII for gynecological and breast cancers, which was the goal of our study.

Methods

PubMed, EMBASE, and Cochrane Library databases were searched to collect the articles exploring the associations of SII with prognostic outcomes [overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), lymph node metastasis (LNM), and lymphovascular invasion (LVI)] in gynecological and breast cancers. The prognostic value of SII was estimated by hazard ratio (HR) or relative risk (RR) with 95% confidence interval (CI).

Results

Nine articles involving 2724 patients in 11 datasets were included. Meta-analysis showed that a high SII index was significantly associated with poor OS (HR = 2.12, 95% CI, 1.61–2.79, P < 0.001), DFS/PFS (HR = 2.28, 95% CI 1.52–3.41, P < 0.001) and an increased risk for LNM (RR = 1.34, 95% CI 1.20–1.50, P < 0.001) in patients with gynecological and breast cancers. Subgroup analysis confirmed the prognostic role of SII for OS was applicable to all cancer types, but the association with DFS/PFS and LNM was only significant for ovarian cancer and breast cancer, especially triple-negative breast cancer. No significant association was detected between SII and LVI.

Conclusion

High SII may be a promising indicator for the prediction of poor prognosis in patients with gynecological and breast cancers, especially ovarian cancer and triple-negative breast cancer.
Predictors of social support, physical health and mental health among food insecure internally displaced persons in Turkana, Kenya
Authors: Gichunge Catherine , Mutiso Daniel , Brynjarsdottir Jenny
Published: August 2020

Background

Food insecurity and the mental and physical health of internally displaced persons (IDPs) is a public health concern. The aim of this study was to determine the predictors of social support, physical and mental health among food insecure IDPs in Nakwamekwei IDP camp in Turkana, Kenya.

Methods

A cross sectional study was conducted among 159 household heads living in the camp. Analysis was conducted using statistical summaries, logistic regression and linear regression.

Results

Ninety four percent (94%) of the households were severely food insecure and the rest of the households had moderate food insecurity. Majority of the household heads (77%) had symptoms of depression and those with five or more children were 3 times (95%CI, 1.31–9.24; p = 0.015) more likely to be have symptoms of depression, while those who were married were less likely to have the same (95%CI, 0.14–0.92; p = 0.038). Seventy six percent (76%) of the household heads had anxiety symptoms; none of the predictor variables were significantly associated with anxiety symptoms in the adjusted analysis. Those who had spent many years in the camp, were older, and had more children had significantly poorer physical health (p = 0.042, p = 0.001, and p = 0.047, respectively). Those who were married and those who had experienced violence in the current camp had significantly higher social support (p = 0.001 and p = 0.006, respectively).

Conclusions

Participants have been living in camp for the last 10 years hence the need to improve their living conditions, address their physical and mental health as well as food insecurity. This can be done by providing the participants with safe drinking water, constructing pit latrines to prevent communicable disease and adhere to the Sphere recommendations for sanitation and hygiene as well as training them in income generating activities to mitigate the high unemployment and food insecurity rates. The IDPs should be integrated into the local community to bring an end to their protracted displacement.
ECCO2R therapy in the ICU: consensus of a European round table meeting
Authors: Combes Alain , Auzinger Georg , Capellier Gilles , du Cheyron Damien , Clement Ian , Consales Guglielmo , Dabrowski Wojciech , De Bels David , de Molina Ortiz Francisco Javier González , Gottschalk Antje , Hilty Matthias P. , Pestaña David , Sousa Eduardo , Tully Redmond , Goldstein Jacques , Harenski Kai
Published: August 2020

Background

With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO2 removal (ECCO2R). However, current evidence in these indications is limited. A European ECCO2R Expert Round Table Meeting was convened to further explore the potential for this treatment approach.

Methods

A modified Delphi-based method was used to collate European experts’ views to better understand how ECCO2R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus.

Results

Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO2R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO2R therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO2R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO2 levels. Driving pressure (≥ 14 cmH2O) followed by plateau pressure (Pplat; ≥ 25 cmH2O) was considered the most important criteria for ECCO2R initiation. Key treatment targets for patients with ARDS undergoing ECCO2R included pH (> 7.30), respiratory rate (< 25 or < 20 breaths/min), driving pressure (< 14 cmH2O) and Pplat (< 25 cmH2O). In ae-COPD, there was consensus that, in patients at risk of non-invasive ventilation (NIV) failure, no decrease in PaCO2 and no decrease in respiratory rate were key criteria for initiating ECCO2R therapy. Key treatment targets in ae-COPD were patient comfort, pH (> 7.30–7.35), respiratory rate (< 20–25 breaths/min), decrease of PaCO2 (by 10–20%), weaning from NIV, decrease in HCO3− and maintaining haemodynamic stability. Consensus was reached on weaning protocols for both indications. Anticoagulation with intravenous unfractionated heparin was the strategy preferred by the group.

Conclusions

Insights from this group of experienced physicians suggest that ECCO2R therapy may be an effective supportive treatment for adults with ARDS or ae-COPD. Further evidence from randomised clinical trials and/or high-quality prospective studies is needed to better guide decision making.
Integrative analyses of single-cell transcriptome and regulome using MAESTRO
Authors: Wang Chenfei , Sun Dongqing , Huang Xin , Wan Changxin , Li Ziyi , Han Ya , Qin Qian , Fan Jingyu , Qiu Xintao , Xie Yingtian , Meyer Clifford A. , Brown Myles , Tang Ming , Long Henry , Liu Tao , Liu X. Shirley
Published: August 2020

We present Model-based AnalysEs of Transcriptome and RegulOme (MAESTRO), a comprehensive open-source computational workflow (http://github.com/liulab-dfci/MAESTRO) for the integrative analyses of single-cell RNA-seq (scRNA-seq) and ATAC-seq (scATAC-seq) data from multiple platforms. MAESTRO provides functions for pre-processing, alignment, quality control, expression and chromatin accessibility quantification, clustering, differential analysis, and annotation. By modeling gene regulatory potential from chromatin accessibilities at the single-cell level, MAESTRO outperforms the existing methods for integrating the cell clusters between scRNA-seq and scATAC-seq. Furthermore, MAESTRO supports automatic cell-type annotation using predefined cell type marker genes and identifies driver regulators from differential scRNA-seq genes and scATAC-seq peaks.
Synchronous solid pseudopapillary neoplasm and invasive ductal carcinoma of the pancreas: a case report
Authors: Tsutsumi Chikanori , Abe Toshiya , Sawatsubashi Yusuke , Tamiya Sadafumi , Kakihara Daisuke , Nishihara Kazuyoshi , Nakano Toru
Published: August 2020

Background

Solid pseudopapillary neoplasm (SPN) of the pancreas is an extremely rare neoplasm with a favorable prognosis. On the other hand, pancreatic invasive ductal carcinoma (IDC) is known to be an aggressive malignancy. To the best of our knowledge, there is no report of SPN combined with IDC of the pancreas.

Case presentation

A 66-year-old woman presented with abnormal genital bleeding and was diagnosed with inoperable cervical cancer. During computed tomography for cancer staging, the patient was incidentally diagnosed with pancreatic cancer. After radiation therapy for the cervical cancer, distal pancreatectomy with D2 lymph node dissection was performed. A postoperative pathological examination revealed SPN with ossification and well-differentiated IDC in the pancreatic body. On immunohistochemical staining, SPN tumor cells showed positive β-catenin and CD10 staining, whereas IDC cells were negative for both. The tumor boundaries were clear. Accordingly, the final pathological diagnosis was synchronous SPN and IDC of the pancreas. Moreover, pathological findings such as the ossification and small number of SPN cells suggested that SPN may have existed long before IDC initiation.

Conclusions

Here, we report the first case of SPN combined with IDC of the pancreas. They may occur independently, and the long-term presence of SPN may lead to the development of IDC.
Diagnostic accuracy of the trans-abdominal ultrasound in the assessment of dysfunctional hemidiaphragm due to non-pulmonic etiology
Authors: Baz Ahmed A. , Aglan Amal Abdel Hakam Mohammed , Mohammed Sabah Ahmed , Sabri Youssriah Yahia
Published: August 2020

Background

To evaluate the role of the trans-abdominal ultrasound (TAUS) in the assessment of hemidiaphragmatic dysfunction—due to non-pulmonic causes—as compared to the conventional CT; 36 patients (22 males and 14 females; age range 5 to 84 years) were included in this study.

Results

In CT examination, the dysfunctional hemidiaphragm was considered when either a hernia/post-traumatic defects (present in 19.4% of patients, of which 5.5% were depicted on the right side and 13.8% were existing on the left side), or elevated copulae (present in 80.6% of patients, of which 58.8% were found on the right side (21 patients) and 22.2% were seen on the left side (8 patients).

The TAUS showed a high sensitivity, specificity, PPV, NPV, and over all accuracy {100% (95% CI = 59.04 to 100.00%), 100% (95% CI = 88.06 to 100.00%), 100%, 100%, 100% (95% CI = 90.26 to 100.00%), respectively} in detection of defects and hernias as compared to CT. A high sensitivity, specificity, PPV, NPV, and over all accuracy {96.55% (95% CI = 82.24 to 99.9%), 100% (95% CI=59.04 to 100.00%), 100%, 87.5% (95% CI = 50.50 to 97.96%), 97.22% (95% CI = 85.47 to 99.93%), respectively} were found in detection of thickness and motion abnormalities, and in the detection of subphrenic collections in cases with relevant elevated copula in CT.

Conclusion

Trans-abdominal ultrasound (TAUS) could accurately assess the diaphragmatic thickness and provides a real-time image of a dysfunctional hemidiaphragm due to a diaphragmatic and infradiaphragmatic causes as well as the diaphragmatic defects with high sensitivity and specificity in comparison to CT.
Macroscopic seismic responses of layered linear anelastic solids: Wave-induced internal deformations beyond the viscoelastic model
Authors: Wang Yichuan , Morozov Igor B.
Published: August 2020

Seismic wave propagation within thinly layered anelastic reservoirs is modeled by direct application of Lagrangian continuum mechanics. Instead of postulating viscoelastic Q-factors or specific microscopic mechanisms, the anelastic properties of the layers are modeled by using generalized macroscopic internal variables. These variables represent averaged measures of various types of internal deformations of the rock, such as relative movements of grains, inclusions, pores and mobile dislocations, wave-induced pore-fluid flows (WIFFs), capillary and layer-boundary effects, or temperature variations. The continuum-mechanics model reveals the existence of body-force (Darcy-type) frictional effects, which are also absent in the viscoelastic model. To implement the attenuation effects observed in laboratory studies, the mechanical properties of the layers are represented by standard linear solid (Zener) rheologies approximating a mesoscopic-scale WIFF effect known as the drained/undrained transition. Optionally, the layer rheologies also include Biot’s poroelastic effects. All compressional- and shear-wave transmission, reflection, and mode-conversion amplitudes and waveforms for primary and secondary waves are modeled at variable angles of incidence. The modeled records exhibit the expected seismic-wave attenuation and dispersion phenomena but differ from the predictions of viscoelastic modeling. The key observation is that wave-propagation effects are sensitive not only to the Q-factors of the layers but also to properties not considered in conventional models: (1) elastic coupling between the internal variables, (2) body-force friction parameters analogous to fluid mobility, and (3) mechanical properties of contact zones between different rocks, such as the effective permeabilities of layer boundaries. Although challenging, these properties of layer boundaries need to be measured for earth’s media and included in the modeling of seismic waves. Another important general observation from this modeling is that the often observed broadband or near-constant seismic Q may result from superposition of the effects of multiple heterogeneities (layers) and material-property contrasts within the medium.
Palladium-Catalyzed [5 + 1] Annulation of Salicylic Acid Derivatives and Propargylic Carbonates
Authors: Sato Kazuya , Ogiwara Yohei , Sakai Norio
Published: August 2020

A palladium-catalyzed annulation reaction between salicylic acid derivatives and propargylic carbonates via the cleavage of a propargylic carbon–oxygen bond is described. This rare annulation reaction uses propargylic compounds as the C1 component for heterocyclic products and can be applied to the preparation of unique five- or six-membered cyclic compounds. The corresponding products contain a fully substituted allylic carbon and the reaction is characterized by high functional-group tolerance.
Trends and controversies in carotid artery stenosis treatment
Authors: Lalla Rakhee , Raghavan Prashant , Chaturvedi Seemant
Published: August 2020

Despite the completion of several multi-center trials, the management of carotid stenosis remains in flux. Key questions include the role of intensive medical management in the treatment of asymptomatic carotid stenosis. In addition, identification of patients with symptomatic stenosis who will most benefit from carotid revascularization remains a priority. The role of newer imaging techniques such as carotid plaque analysis with magnetic resonance imaging is also challenging current treatment paradigms. These topics are explored in this topical update.
Development and validation of a sensitive HPLC-HESI-MS/MS method for quantitative determination of bitopertin in rat and marmoset plasma
Authors: Frouni Imane , Gaudette Fleur , Bédard Dominique , Nuara Stephen G. , Kwan Cynthia , Hamadjida Adjia , Gourdon Jim C. , Beaudry Francis , Huot Philippe
Published: August 2020

Bitopertin is a potent glycine transporter 1 (GlyT1) inhibitor that has undergone clinical trials for diverse disorders and has a well-documented pharmacokinetic (PK) profile in humans. Even though pre-clinical studies have demonstrated potential therapeutic effects on cognition and neuropathic pain, the PK profile of bitopertin in the rat has been partly disclosed and no study reporting its PK profile in the common marmoset has been published. The aim of this study was to develop and validate a sensitive and selective high-performance liquid chromatography coupled with heat assisted electrospray ionisation tandem mass spectrometry (HPLC-HESI-MS/MS) assay to quantify bitopertin in the rat (Sprague-Dawley) and the common marmoset (Callithrix jacchus) plasma after administration of 1.0 mg/kg subcutaneously. The analytical method consisted of protein precipitation followed by HPLC-HESI–MS/MS. Chromatographic separation was carried out on a Thermo Scientific Aquasil C18 analytical column (100 x 2.1 mm I.D., 5.0 μm) kept at 50°C using acetonitrile and water both fortified at 0.1% (v/v) with formic acid at a ratio 55:45 as mobile phase with a constant flow rate of 250 μL/min. The calibration function was linear in the range of 0.3-200.0 ng/mL in rat plasma. The intra-day and inter-day precision and accuracy were within ± 15% at all concentrations. The limit of detection (LOD) and quantitation (LOQ) in rat plasma were 0.08 and 0.3 ng/mL, respectively. This method has demonstrated high sensitivity and specificity and was successfully applied to measure bitopertin in rat and marmoset plasma, allowing the investigation of its PK properties in both species.