bluuebunny/crossref_metadata_2025 huggingface dataset:
Atraumatic Splenic Rupture in a Patient on Apixaban and Dual Antiplatelet Therapy
Authors: Natarajan Piruthiviraj , Thangarasu Sudhagar , Ruck Lela , Estrada Paul , Gajendran Mahesh , Renganathan Gowri , Prakash Bharat Ved , Aduroja Olufemi
Published: June 2021

Splenic rupture due to any cause is a life-threatening complication and commonly attributed to trauma. Atraumatic splenic rupture is very rarely reported, and the incidence is currently unknown. Anticoagulants and dual anti-platelet medication can increase the chances of a splenic rupture. Surgical removal of the spleen may be warranted to prevent a life-threatening bleeding. Early identification and intervention are required for most patients as only a few qualify for medical management.
Direct P70S6K1 inhibition to replace dexamethasone in synergistic combination with MCL-1 inhibition in multiple myeloma
Authors: Spaan Ingrid , Timmerman Laura M. , Kimman Thomas , Slomp Anne , Cuenca Marta , van Nieuwenhuijzen Niels , Moesbergen Laura M. , Minnema Monique C. , Raymakers Reinier A. , Peperzak Victor
Published: June 2021

Novel combination therapies have markedly improved the lifespan of patients with multiple myeloma (MM), but drug resistance and disease relapse remain major clinical problems. Dexamethasone and other glucocorticoids are a cornerstone of conventional and new combination therapies for MM, although their use is accompanied by serious side effects. We aimed to uncover drug combinations that act in synergy and, as such, allow reduced dosing while remaining effective. Dexamethasone and the myeloid cell leukemia 1 (MCL-1) inhibitor S63845 (MCL-1i) proved the most potent combination in our lethality screen and induced apoptosis of human myeloma cell lines (HMCLs) that was 50% higher compared with an additive drug effect. Kinome analysis of dexamethasone-treated HMCLs revealed a reduction in serine/threonine peptide phosphorylation, which was predicted to result from reduced Akt activity. Biochemical techniques showed no dexamethasone-induced effects on FOXO protein or GSK3 but did show a 50% reduction in P70S6K phosphorylation, downstream of the Akt-mTORC1 axis. Replacing dexamethasone by the P70S6K1 isoform-specific inhibitor PF-4708671 (S6K1i) revealed similar and statistically significant synergistic apoptosis of HMCLs in combination with MCL-1i. Interestingly, apoptosis induced by the P70S6K1i and MCL-1i combination was more-than-additive in all 9 primary MM samples tested; this effect was observed for 6 of 9 samples with the dexamethasone and MCL-1i combination. Toxicity on stem and progenitor cell subsets remained minimal. Combined, our results show a strong rationale for combination treatments using the P70S6K inhibitor in MM. Direct and specific inhibition of P70S6K may also provide a solution for patients ineligible or insensitive to dexamethasone or other glucocorticoids.
A novel approach to minimally invasive hysterectomy without the use of a uterine manipulator: Kamran’s TLH
Authors: Gendia Ahmed M. , Donlon Noel E. , Kamran Waseem M.
Published: June 2021

Background

Hysterectomy remains one of the most common major gynaecological procedures, with total laparoscopic hysterectomy (TLH) now established as the technique of choice over conventional open approaches. This approach depends on the use of a uterine manipulator to facilitate uterine retraction and colpotomy. This study describes a novel approach in performing total laparoscopic hysterectomy without the use of uterine manipulator or vaginal tubes and reports the intra- and postoperative outcome of this technique.

Methods

A single-centre retrospective analysis of patients who underwent TLH without uterine manipulator or vaginal tube “Kamran’s TLH” for benign conditions was performed from January 2017 to October 2019. Data collected included patients’ demographics, intraoperative finding and postoperative course.

Results

A total of eighty-six hysterectomies were performed utilizing the Kamran’s TLH (KTLH) approach. Mean age was 52.2 (± 11) years old and BMI was 28.2 (± 7). TLH with bilateral salpingo-oophorectomy was performed in 63 (73.3%) patients and TLH with preservation of ovaries in 23 (26.7%) patients. Mean operative time was 64.7 (± 27.9) min and estimated bloods loss was 46.2 (± 54.6) ml. No intraoperative complications were recorded and there was no conversion to open surgery. Only one patient required readmission and surgery for vaginal vault dehiscence during their postoperative course.

Conclusion

Uterine manipulator is a key component in performing laparoscopic hysterectomy. However, our approach demonstrated that TLH can be safely performed without the use of any uterine or vaginal manipulation.
Characterization of contrasting rice (Oryza sativa L.) genotypes reveals the Pi-efficient schema for phosphate starvation tolerance
Authors: Kumar Suresh , Pallavi  , Chugh Chetna , Seem Karishma , Kumar Santosh , Vinod K. K. , Mohapatra Trilochan
Published: June 2021

Background

Phosphorus (P), being one of the essential components of nucleic acids, cell membranes and enzymes, indispensable for diverse cellular processes like photosynthesis/carbohydrate metabolism, energy production, redox homeostasis and signaling. Crop yield is severely affected due to Phosphate (Pi) deficiency; and to cope with Pi-deficiency, plants have evolved several strategies. Some rice genotypes are compatible with low Pi availability, whereas others are sensitive to Pi deficiency. However, the underlying molecular mechanism for low Pi tolerance remains largely unexplored.

Result

Several studies were carried out to understand Pi-deficiency responses in rice at seedling stage, but few of them targeted molecular aspects/responses of Pi-starvation at the advanced stage of growth. To delineate the molecular mechanisms for low Pi tolerance, a pair of contrasting rice (Oryza sativaL.) genotypes [viz.Pusa-44 (Pi-deficiency sensitive) and its near isogenic line (NIL-23, Pi-deficiency tolerant) harboringPhosphorus uptake 1(Pup1) QTL from anauslandrace Kasalath] were used. Comparative morphological, physiological, and biochemical analyses confirmed some of the well-known findings. Transcriptome analysis of shoot and root tissues from 45-day-old rice plants grown hydroponically under P-sufficient (16 ppm Pi) or P-starved (0 ppm Pi) medium revealed that Pi-starvation stress causes global transcriptional reprogramming affecting several transcription factors, signaling pathways and other regulatory genes. We could identify several significantly up-regulated genes in roots of NIL-23 under Pi-starvation which might be responsible for the Pi starvation tolerance. Pathway enrichment analysis indicated significant role of certain phosphatases, transporters, transcription factors, carbohydrate metabolism, hormone-signaling, and epigenetic processes in improving P-starvation stress tolerance in NIL-23.

Conclusion

We report the important candidate mechanisms for Pi acquisition/solubilization, recycling, remobilization/transport, sensing/signalling, genetic/epigenetic regulation, and cell wall structural changes to be responsible for P-starvation tolerance in NIL-23. The study provides some of the novel information useful for improving phosphorus-use efficiency in rice cultivars.
Development and validation of a risk index to predict kidney graft survival: the kidney transplant risk index
Authors: Senanayake Sameera , Kularatna Sanjeewa , Healy Helen , Graves Nicholas , Baboolal Keshwar , Sypek Matthew P. , Barnett Adrian
Published: June 2021

Background

Kidney graft failure risk prediction models assist evidence-based medical decision-making in clinical practice. Our objective was to develop and validate statistical and machine learning predictive models to predict death-censored graft failure following deceased donor kidney transplant, using time-to-event (survival) data in a large national dataset from Australia.

Methods

Data included donor and recipient characteristics (n = 98) of 7,365 deceased donor transplants from January 1st, 2007 to December 31st, 2017 conducted in Australia. Seven variable selection methods were used to identify the most important independent variables included in the model. Predictive models were developed using: survival tree, random survival forest, survival support vector machine and Cox proportional regression. The models were trained using 70% of the data and validated using the rest of the data (30%). The model with best discriminatory power, assessed using concordance index (C-index) was chosen as the best model.

Results

Two models, developed using cox regression and random survival forest, had the highest C-index (0.67) in discriminating death-censored graft failure. The best fitting Cox model used seven independent variables and showed moderate level of prediction accuracy (calibration).

Conclusion

This index displays sufficient robustness to be used in pre-transplant decision making and may perform better than currently available tools.
Sepsis-related hospital admissions and ambient air pollution: a time series analysis in 6 Chinese cities
Authors: Wang Yu , Liu Zhen , Yang Lian , Zhou Jiushun , Li Jia , Liao Hai Lun , Tian Xing Jun
Published: June 2021

Background

Some prevalent but rarely studied causes of hospital admissions, such as sepsis is still unknown whether affected by air pollution.

Methods

We used time-series regression within generalized additive models to estimate the effect of air pollutant level on the sepsis-related hospital admissions, for the years 2017–18, using data from six cities in Sichuan, China. Potential effect modifications by age and sex were also explored. The effects of air pollutant on hospital stays for sepsis were also quantified.

Results

Positive associations between short-term exposure to NO2 and O3 and risk of sepsis-related hospital admissions and stays were found. Each 10 μg/m3 increase in short-term NO2 at lag 03 and O3 at lag 4 was associated with an increase of 2.76% (95% CI: 0.67, 4.84%) and 0.64% (95% CI: 0.14, 1.14%) hospital admissions, respectively. An increase of 0.72% (95% CI: 0.05, 1.40%) hospital stay was associated with 10 μg/m3 increase in O3 concentration at lag 4. Besides, the adverse effect of exposure to NO2 was more significant in males and population aged less than 14 years; while more significant in females and population aged 14 ~ 65 and over 65 years for exposure to O3. These associations remained stable after the adjustment of other air pollutants.8.

Conclusion

Exposure to ambient NO2 and O3 may cause substantial sepsis hospitalizations, and hospital stays in Sichuan, China. These associations were different in subgroup by age and sex.
The role of FOLFIRINOX in metastatic pancreatic cancer: a meta-analysis
Authors: Zhang Beilei , Zhou Fengyan , Hong Jiaze , Ng Derry Minyao , Yang Tong , Zhou Xinyu , Jin Jieyin , Zhou Feifei , Chen Ping , Xu Yunbao
Published: June 2021

Background

The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC.

Methods

We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS).

Results

We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, p<0.001) but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than monochemotherapy (HR 0.59, 95% Cl 0.52–0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR 0.76, 95% Cl 0.61–0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR 0.91, 95% Cl 0.82–1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea.

Conclusion

These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors.

Graphical abstract
The household financial burden of non-communicable diseases in low- and middle-income countries: a systematic review
Authors: Kazibwe Joseph , Tran Phuong Bich , Annerstedt Kristi Sidney
Published: June 2021

Background

The chronic nature of noncommunicable diseases (NCD) and costs associated with long-term care can result in catastrophic health expenditure for the patient and their household pushing them deeper into poverty and entrenching inequality in society. As the full financial burden of NCDs is not known, the objective of this study was to explore existing evidence on the financial burden of NCDs in low- and middle-income countries (LMICs), specifically estimating the cost incurred by patients with NCDs and their households to inform the development of strategies to protect such households from catastrophic expenditure.

Methods

This systematic review followed the PRISMA guidelines, PROSPERO: CRD42019141088. Eligible studies published between 1st January 2000 to 7th May 2020 were systematically searched for in three databases: Medline, Embase and Web of Science. A two-step process, comprising of qualitative synthesis proceeded by quantitative (cost) synthesis, was followed. The mean costs are presented in 2018 USD.

Findings

51 articles were included, out of which 41 were selected for the quantitative cost synthesis. Most of the studies were cross-sectional cost-of-illness studies, of which almost half focused on diabetes and/or conducted in South-East Asia. The average total costs per year to a patient/household in LMICs of COPD, CVD, cancers and diabetes were $7386.71, $6055.99, $3303.81, $1017.05, respectively.

Conclusion

This review highlighted major data and methodological gaps when collecting data on costs of NCDs to households along the cascade of care in LMICs. More empirical data on cost of specific NCDs are needed to identify the diseases and contexts where social protection interventions are needed most. More rigorous and standardised methods of data collection and costing for NCDs should be developed to enable comprehensive and comparable evidence of the economic and financial burden of NCDs to patients and households in LMICs. The available evidence on costs reveals a large financial burden imposed on patients and households in seeking and receiving NCD care and emphasizes the need for adequate and reliable social protection interventions to be implemented alongside Universal Health Coverage.
The missing link between legal age of sexual consent and age of marriage in sub-Saharan Africa: implications for sexual and reproductive health and rights
Authors: Ahinkorah Bright Opoku , Okyere Joshua , Hagan John Elvis , Seidu Abdul-Aziz , Aboagye Richard Gyan , Yaya Sanni
Published: June 2021

Child marriage is a fundamental violation of human rights and a threat to access to education, sexual and reproductive health care, and employment. It also threatens freedom from violence, reproductive rights, movement, and the right to consensual marriage. In most countries in sub-Saharan Africa, the legal age of marriage is 18 years. Hence, girls who marry before 18 years are considered as victims of child marriage. Closely knitted to legal age for marriage is the issue of age for sexual consent, which refers to the minimum age at which a person is considered to have the legal capacity to consent to sexual intercourse. While there seem to be a standard legal age for marriage, the legal age for sexual consent varies in most countries in sub-Saharan Africa and is often lower than the legal age of marriage. In this commentary, we argue that the gap between the legal age of sexual consent and marriage partly accounts for some of the sexual and reproductive health challenges such as intimate partner violence, sexually transmitted infections, adolescent pregnancy, early childbirth, including unsafe abortions among adolescent girls in sub-Saharan Africa and infringements on their sexual and reproductive health rights. This commentary highlights strategic potential interventions that could help address the identified gaps. We argue that aligning the age for sexual consent and marriage is not the solution to the problem. However, what is critical is the education of young people about sexual and reproductive health issues and comprehensive sexuality education through advocacy networks at the national and local levels. Thus, the key is to provide accurate, timely, and non-judgmental sexual and reproductive health and rights information to young people irrespective of the prevailing age of consent. This provision will empower them to make informed decisions about their sexual and reproductive health.
Designing the next generation of implementation research training for learners in low- and middle-income countries
Authors: Penkunas Michael J. , Chong Shiau Yun , Rhule Emma L. M. , Berdou Evangelia , Allotey Pascale
Published: June 2021

Efficacious health interventions tested through controlled trials often fail to show desired impacts when implemented at scale. These challenges can be particularly pervasive in low- and middle-income settings where health systems often lack the capacity and mechanisms required for high-quality research and evidence translation. Implementation research is a powerful tool for identifying and addressing the bottlenecks impeding the success of proven health interventions. Implementation research training initiatives, although growing in number, remain out of reach for many investigators in low- and middle-income settings, who possess the knowledge required to contextualize challenges and potential solutions in light of interacting community- and system-level features. We propose a realigned implementation research training model that centers on team-based learning, tailored didactic opportunities, learning-by-doing, and mentorship.
Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors
Authors: Li Jian , Deng Yanhong , Zhang Weijie , Zhou Ai-Ping , Guo Weijian , Yang Jianwei , Yuan Ying , Zhu Liangjun , Qin Shukui , Xiang Silong , Lu Haolan , Gong John , Xu Ting , Liu David , Shen Lin
Published: June 2021

Background

Monoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion. Envafolimab, a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment, represents a potential advance because it can be conveniently administered subcutaneously.

Methods

This open-label, single-arm, phase 2 study evaluated the efficacy and safety of envafolimab in patients with previously treated advanced dMMR/MSI-H tumors from 25 clinical sites across China. Adults with histologically confirmed locally advanced or metastatic malignant dMMR/MSI-H solid tumors received weekly 150 mg subcutaneous envafolimab injections in a 28-day treatment cycle. The primary efficacy endpoint was the objective response rate (assessed by a blinded independent review committee). Secondary efficacy outcomes were disease control rate, duration of response, progression-free survival, and overall survival.

Results

One hundred and three patients (65 with colorectal cancer, 18 with gastric cancer, and 20 with other solid tumors) were enrolled. Median follow-up was 11.5 months. The objective response rate was 42.7% (95% confidence interval [CI] 33.0–52.8), and the disease control rate was 66.0% (95% CI 56.0–75.1). Median duration of response was not reached; the duration of response rate at 12 months was 92.2% (95% CI 77.5–97.4). Median progression-free survival was 11.1 months (95% CI 5.5 to not evaluable). Overall survival at 12 months was 74.6% (95% CI 64.7–82.1). Sixteen patients (16%) had at least one grade 3 or 4 related treatment-emergent adverse event. No grade 5 treatment-emergent adverse events related to envafolimab were reported. Injection site reactions, all grade 1–2, were reported in nine patients (9%), but there were no infusion reactions. Eight patients (8%) had grade 3 or 4 immune-related adverse events.

Conclusions

This is the first pivotal phase 2 study to examine the efficacy and safety of a single-domain immune checkpoint antibody in the treatment of cancer. Envafolimab was effective and had acceptable safety in the treatment of previously treated advanced dMMR/MSI-H solid tumors. As the first single-domain PD-L1-targeting antibody administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treatment of cancer.

Trial registrationClinicalTrials.gov, NCT03667170. Registered 10 September 2018—Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT03667170.
Current approach and novel perspectives in nasopharyngeal carcinoma: the role of targeting proteasome dysregulation as a molecular landmark in nasopharyngeal cancer
Authors: Yarza Ramon , Bover Mateo , Agulló-Ortuño Maria Teresa , Iglesias-Docampo Lara Carmen
Published: June 2021

Nasopharyngeal carcinoma (NPC) represents a molecularly paradigmatic tumor given the complex diversity of environmental as well as host dependent factors that are closely implicated in tissue transformation and carcinogenesis. Epstein Barr Virus (EBV) plays a key role in tissue invasion, hyperplasia and malignant transformation. Therefore, EBV related oncoviral proteins such as Latent Membrane Protein family (LMP1, LMP2), Epstein Barr Nuclear Antigen 1 (EBNA1) and EBV related glycoprotein B (gB) are responsible for inducing intracellular signalling aberrations leading to sustained proliferation and further acquisition of NPC related invasive nature and metastatic potential.

Dysregulation of proteasome signaling seems to be centrally implicated in oncoviral protein stabilization as well as in modulating tumor microenvironment. Different studies in vitro and in vivo suggest a potential role of proteasome inhibitors in the therapeutic setting of NPC. Furthermore, alterations affecting proteasome signalling in NPC have been associated to tumor growth and invasion, distant metastasis, immune exclusion and resistance as well as to clinical poor prognosis. So on, recent studies have shown the efficacy of immunotherapy as a suitable therapeutic approach to NPC. Nevertheless, novel strategies seem to look for combinatorial regimens aiming to potentiate immune recognition as well as to restore both primary and acquired immune resistance.

In this work, our goal is to thoroughly review the molecular implications of proteasome dysregulation in the molecular pathogenesis of NPC, together with their direct relationship with EBV related oncoviral proteins and their role in promoting immune evasion and resistance. We also aim to hypothesize about the feasibility of the use of proteasome inhibitors as part of immunotherapy-including combinatorial regimens for their potential role in reversing immune resistance and favouring tumor recognition and eventual tumor death.
The ROX index as a predictor of standard oxygen therapy outcomes in thoracic trauma
Authors: Cornillon Adrien , Balbo Juliette , Coffinet Julien , Floch Thierry , Bard Mathieu , Giordano-Orsini Guillaume , Malinovsky Jean-Marc , Kanagaratnam Lukshe , Michelet Daphne , Legros Vincent
Published: June 2021

Background

Thoracic trauma is commonplace and accounts for 50–70% of the injuries found in severe trauma. Little information is available in the literature as to timing of endotracheal intubation. The main objective of this study was to assess the accuracy of the ROX index in predicting successful standard oxygen (SO) therapy outcomes, and in pre-empting intubation.

Methods

Patient selection included all thoracic trauma patients treated with standard oxygen who were admitted to a Level I trauma center between January 1, 2013 and April 30, 2020. Successful standard SO outcomes were defined as non-requirement of invasive mechanical ventilation within the 7 first days after thoracic trauma.

Results

One hundred seventy one patients were studied, 49 of whom required endotracheal intubation for acute respiratory distress (28.6%). A ROX index score ≤ 12.85 yielded an area under the ROC curve of 0.88 with a 95% CI [0.80–0.94], 81.63sensitivity, 95%CI [0.69–0.91] and 88.52 specificity, 95%CI [0.82–0.94] involving a Youden index of 0.70. Patients with a median ROX index greater than 12.85 within the initial 24 h were less likely to require mechanical ventilation within the initial 7 days of thoracic trauma.

Conclusion

We have shown that a ROX index greater than 12.85 at 24 h was linked to successful standard oxygen therapy outcomes in critical thoracic trauma patients. It is our belief that an early low ROX index in the initial phase of trauma should heighten vigilance on the part of the attending intensivist, who has a duty to optimize management.
Modified CIM test as a useful tool to detect carbapenemase activity among extensively drug-resistant Klebsiella pneumoniae, Escherichia coli and Acinetobacter baumannii
Authors: Zahedi Bialvaei Abed , Dolatyar Dehkharghani Alireza , Asgari Farhad , Shamloo Firouzeh , Eslami Parisa , Rahbar Mohammad
Published: June 2021

Purpose

Timely detection of carbapenemases is essential for developing strategies to control the spread of infections by carbapenem-resistant isolates. The purpose of this study was to determine the epidemiology of carbapenemase genes among carbapenem-resistant isolates of Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. In addition, the efficacy of the modified Hodge test (MHT), Carba NP test, and modified carbapenem inactivation method (mCIM) were compared.

Methods

A total of 122 carbapenem-resistant clinical isolates including 77 K. pneumoniae, 39 A. baumannii, and six E. coli were collected from hospitalized patients. Three phenotypic methods, including the MHT, Carba NP test, and mCIM were used for investigation of carbapenemase production. In addition, polymerase chain reaction (PCR) was performed to detect carbapenemase-encoding genes.

Result

The sensitivity and specificity of the MHT were 75.0% and 100%, respectively. In addition, Carba NP displayed 80.8% sensitivity and 100% specificity, whereas the sensitivity and specificity were 90.4% and 100% for the mCIM test, respectively. Among carbapenem-resistant isolates, 70, 84, and 87 isolates exhibited positive results according to the MHT, Carba NP test, and mCIM, respectively. PCR indicated the presence of one or more carbapenemase genes in 119 of carbapenem-resistant isolates, with blaKPC and blaVIM being the most commonly encountered. Co-production of ‘KPC and OXA-48’, ‘KPC and VIM’, and ‘KPC and IMP’ was detected in three, nine, and seven isolates, respectively.

Conclusion

Our results confirm that the mCIM test is a useful tool for the reliable detection of carbapenemase activity in enterobacterial isolates, especially in clinical microbiological laboratories with limited resources.
Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia
Authors: Li Yuejiao , Dong Yankai , Ran Ye , Zhang Yanan , Wu Boyao , Xie Jundong , Cao Yanpei , Mo Miaohua , Li Sen , Deng Hao , Hao Wenbo , Yu Shengyuan , Wu Yaojiong
Published: June 2021

Background

We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved.

Methods

Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq.

Results

We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke.

Conclusions

Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.
Impact resistance of steel materials to ballistic ejecta and shelter development using steel deck plates
Authors: Yamada Hiroyuki , Tateyama Kohei , Naruke Shino , Sasaki Hisashi , Torigata Shinichi , Honda Ryo , Kubo Tomohiro , Yoshimoto Mitsuhiro , Fujii Toshitsugu
Published: June 2021

The destruction caused by ballistic ejecta from the phreatic eruptions of Mt. Ontake in 2014 and Mt. Kusatsu-Shirane (Mt. Moto-Shirane) in 2018 in Japan, which resulted in numerous casualties, highlighted the need for better evacuation facilities. In response, some mountain huts were reinforced with aramid fabric to convert them into shelters. However, a number of decisions must be made when working to increase the number of shelters, which depend on the location where they are to be built. In this study, we propose a method of using high-strength steel to reinforce wooden buildings for use as shelters. More specifically, assuming that ballistic ejecta has an impact energy of 9 kJ or more, as in previous studies, we developed a method that utilizes SUS304 and SS400 unprocessed steel plates based on existing impact test data. We found that SUS304 is particularly suitable for use as a reinforcing material because it has excellent impact energy absorption characteristics due to its high ductility as well as excellent corrosion resistance. With the aim of increasing the structural strength of steel shelters, we also conducted an impact test on a shelter fabricated from SS400 deck plates (i.e., steel with improved flexural strength provided by work-hardened trapezoidal corrugated plates). The results show that the shelter could withstand impact with an energy of 13.5 kJ (2.66 kg of simulated ballistic ejecta at 101 m/s on impact). In addition, from the result of the impact test using the roof-simulating structure, it was confirmed the impact absorption energy is further increased when artificial pumice as an additional protective layer is installed on this structure. Observations of the shelter after the impact test show that there is still some allowance for deformation caused by projectile impact, which means that the proposed steel shelter holds promise, not only structurally, but also from the aspects of transportation and assembly. Hence, the usefulness of shelters that use steel was shown experimentally. However, shelter construction should be suitable for the target environment.
Health outcomes of sexual and gender minorities after cancer: a systematic review
Authors: Pratt-Chapman Mandi L. , Alpert Ash B. , Castillo Daniel A.
Published: June 2021

Purpose

Cancer research on sexual and gender minority (SGM) populations is gaining momentum. The purpose of this systematic review was to examine what is currently known in the research literature regarding patient-reported health outcomes after cancer treatment among SGM populations.

Methods

In March 2021, a medical librarian conducted a systematic keyword search on PubMed, Embase, Scopus, Web of Science, PsycINFO, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials. The primary inclusion criterion was assessment of at least one physical, psychosocial, emotional, or functional patient-reported health outcome related to the impacts of cancer diagnosis and/or treatment. Articles that met inclusion criteria were reviewed in their entirety, charted in a Word Table, and assessed for quality. Quality considerations included study design, sampling approach, diversity of sample, measures used, and analytic procedures. Studies were synthesized based on type of cancer study participants experienced.

Results

Sixty-four studies were included in the final analysis: most were quantitative, secondary analyses or cross-sectional studies with convenience samples, and focused on people with a history of breast or prostate cancer. Differences between sexual minority men and women in terms of coping and resilience were noted. Few studies reported on experiences of transgender persons and none reported on experiences of intersex persons.

Conclusions

A growing literature describes the patient-reported health outcomes of SGM people with a history of cancer. This study summarizes important between-group differences among SGM and heterosexual, cisgender counterparts that are critical for clinicians to consider when providing care.

Implications for cancer survivors

Sexual orientation and gender identity are relevant to cancer survivors’ health outcomes. Subgroups of SGM people have differential experiences and outcomes related to cancer and its impacts.
Existence and optimal controls for nonlocal fractional evolution equations of order (1,2) in Banach spaces
Authors: Pang Denghao , Jiang Wei , Niazi Azmat Ullah Khan , Sheng Jiale
Published: June 2021

In this paper, we mainly investigate the existence, continuous dependence, and the optimal control for nonlocal fractional differential evolution equations of order (1,2) in Banach spaces. We define a competent definition of a mild solution. On this basis, we verify the well-posedness of the mild solution. Meanwhile, with a construction of Lagrange problem, we elaborate the existence of optimal pairs of the fractional evolution systems. The main tools are the fractional calculus, cosine family, multivalued analysis, measure of noncompactness method, and fixed point theorem. Finally, an example is propounded to illustrate the validity of our main results.
Resonant interaction of relativistic electrons with realistic electromagnetic ion–cyclotron wave packets
Authors: Grach Veronika S. , Demekhov Andrei G. , Larchenko Alexey V.
Published: June 2021

We study the influence of real structure of electromagnetic ion-cyclotron wave packets in the Earth’s radiation belts on precipitation of relativistic electrons. Automatic algorithm is used to distinguish isolated elements (wave packets) and obtain their amplitude and frequency profiles from satellite observations by Van Allen Probe B. We focus on rising-tone EMIC wave packets in the proton band, with a maximum amplitude of 1.2–1.6 nT. The resonant interaction of the considered wave packets with relativistic electrons 1.5–9 MeV is studied by numerical simulations. The precipitating fluxes are formed as a result of both linear and nonlinear interaction; for energies 2–5 MeV precipitating fluxes are close to the strong diffusion limit. The evolution of precipitating fluxes is influenced by generation of higher-frequency waves at the packet trailing edge near the equator and dissipation of lower-frequency waves in the $$\text {He}^+$$

He
+

cyclotron resonance region at the leading edge. The wave packet amplitude modulation leads to a significant change of precipitated particles energy spectrum during short intervals of less than 1 minute. For short time intervals about 10–15 s, the approximation of each local amplitude maximum of the wave packet by a Gaussian amplitude profile and a linear frequency drift gives a satisfactory description of the resonant interaction.
Feasibility, Acceptability, and Preliminary Effectiveness of a Compassion-Centered Team Intervention to Improve Clinical Research Coordinator Resilience and Well-Being
Authors: Mascaro Jennifer S. , Palmer Patricia K. , Ash Marcia J. , Peacock Caroline , Sharma Anuja , Escoffery Cam , Raison Charles
Published: June 2021

PURPOSE:

Oncology clinical research coordinators (CRCs) and team-based coordinator care are critical for the success of clinical trials. However, CRCs typically report elevated anxiety and burnout and many oncology centers have high levels of coordinator attrition. To address the need for a team-based intervention to reduce burnout and promote resilience and cohesion among CRCs, we developed a compassion-centered, team-based intervention, Compassion-Centered Spiritual Health Team Intervention (CCSH-TI).

METHODS:

Participants were CRCs working in disease-specific teams within a comprehensive cancer center. CRCs were randomly assigned by team to either participate in four 60-minute sessions of CCSH-TI or receive the intervention after the study. To evaluate whether CCSH-TI is feasible and acceptable, we used a mixed-method approach including self-report questionnaires and a focus group. To evaluate the impact of CCSH-TI, we assessed self-reported resilience, well-being, burnout, and team civility before and immediately after the intervention period (ClinicalTrials.gov identifier: NCT04060901 ).

RESULTS:

Attendance varied by team, but all teams had rates more than 60%. Coordinators rated high levels of credibility of CCSH-TI to improve burnout, and the majority reported that they received benefits, particularly in resilience and stress management, indicating acceptability. Coordinators randomly assigned to CCSH-TI reported an increase in resilience compared with coordinators randomly assigned to the wait-list group (F(41) = 4.53, P = .039).

CONCLUSION:

Data from this pilot study indicate that CCSH-TI may be a feasible, credible, acceptable, and effective intervention to augment individual resilience among CRCs. However, the quantitative and qualitative data suggest that more comprehensive and systematic programming is necessary to truly mitigate burnout.
Dante and Cecco d’Ascoli on Love and Compulsion: The Epistle to Cino,Io sono stato, the Third Heaven
Authors: Barolini Teodolinda
Published: June 2021

Arguing that Dante ultimately views compulsion in the erotic sphere as part and parcel of compulsion in the properly philosophical sphere, aka determinism, this article traces Dante’s variable thinking on this core issue as he veers from a moralistic view in the Vita Nuova to a more “scientific” view in the third epistle and again to a moralistic view in the Commedia (whose circle of lust boasts, in the wind that buffets the lustful, an example of compulsion borrowed from Nicomachean Ethics 3.1). The philosopher and astrologer Cecco d’Ascoli is a contemporary witness to the philosophical importance of these issues: in his philosophical poem Acerba, Cecco attacks Dante’s love poetry for harboring deterministic belief.
What Is (Machine) Philosophy?
Authors: Parisi Luciana , Morgan William
Published: June 2021

This interview with the digital media theorist Luciana Parisi opens with the hypothesis that cybernetics is not merely the name for that postwar metascience of command and control. For Parisi, cybernetics names a “historical reconfiguration of metaphysics on behalf of technics.” This interview asks about the meaning and consequences of this hypothesis but steers away from the all-too-easy poiesis-as-panacea solution to the computational quagmire. Instead, this interview descends into the computational medium, into the specificity of its logic, asking what it might mean not merely to live in a cyberneticized world but to actively participate and believe in such a world. Parisi’s response puts to philosophy an important task: not to seek the accommodations of an expanding concept of the human within a machinic world but to think with the logic of the ascendant cybernetic metaphysics. For Parisi, a necessary move herein is to negotiate the reality of the algorithm’s syntactic operations, their performativity, a move that for her implies a certain form of belief. In tracking this form of belief across disciplines, this interview broaches questions of scalability, race and colonialism, the nonneutrality of technoscience, and the potential of computational aesthetics. Finally, the interview gestures toward Parisi’s future work, because, as she reminds us, we cannot go back; there are questions emerging from within machines that are eager to emerge and are waiting for us to think them.
Loss of acentriolar MTOCs disrupts spindle pole Aurora A and assembly of the liquid-like meiotic spindle domain in oocytes
Authors: Wang Xiaotian , Baumann Claudia , De La Fuente Rabindranath , Viveiros Maria M.
Published: June 2021

Oocyte-specific knockdown of pericentrin (PCNT) in transgenic (Tg) mice disrupts acentriolar microtubule-organizing center (aMTOC) formation, leading to spindle instability and error-prone meiotic division. Here, we show that PCNT-depleted oocytes lack phosphorylated Aurora A (pAURKA) at spindle poles, while overall levels are unaltered. To test aMTOC-associated AURKA function, metaphase II (MII) control (WT) and Tg oocytes were briefly exposed to a specific AURKA inhibitor (MLN8237). Similar defects were observed in Tg and MLN8237-treated WT oocytes, including altered spindle structure, increased chromosome misalignment and impaired microtubule regrowth. Yet, AURKA inhibition had a limited effect on Tg oocytes, revealing a critical role for aMTOC-associated AURKA in regulating spindle stability. Notably, spindle instability was associated with disrupted γ-tubulin and lack of the liquid-like meiotic spindle domain (LISD) in Tg oocytes. Analysis of this Tg model provides the first evidence that LISD assembly depends expressly on aMTOC-associated AURKA, and that Ran-mediated spindle formation ensues without the LISD. These data support that loss of aMTOC-associated AURKA and failure of LISD assembly contribute to error-prone meiotic division in PCNT-depleted oocytes, underscoring the essential role of aMTOCs for spindle stability.
Rapid stress hardening in the Antarctic midge improves male fertility by increasing courtship success and preventing decline of accessory gland proteins following cold exposure
Authors: Ajayi Oluwaseun M. , Gantz J. D. , Finch Geoffrey , Lee Richard E. , Denlinger David L. , Benoit Joshua B.
Published: June 2021

Rapid hardening is a process that quickly improves an animal's performance following exposure to potentially damaging stress. In this study of the Antarctic midge, Belgica antarctica (Diptera, Chironomidae), we examined how rapid hardening in response to dehydration (RDH) or cold (RCH) improves male pre- and post-copulatory function when the insects are subsequently subjected to a damaging cold exposure. Neither RDH nor RCH improved survival in response to lethal cold stress, but male activity and mating success following sublethal cold exposure were enhanced. Egg viability decreased following direct exposure of the mating males to sublethal cold but improved following RCH and RDH. Sublethal cold exposure reduced the expression of four accessory gland proteins, while expression remained high in males exposed to RCH. Though rapid hardening may be cryptic in males, this study shows that it can be revealed by pre- and post-copulatory interactions with females.
Silent Sources of the History of Epidemics in the Islamic World: Literature on Ṭāʿūn/Plague Treatises
Authors: Arıcı Mustakim
Published: June 2021

From 1347 onwards, new literature emerged in the Islamic and Western worlds: the Ṭā‘ūn [Plague] Treatises. The literature in Islamdom was underpinned by three things: (i) Because the first epidemic was a phenomenon that had been experienced since the birth of Islam, ṭā‘ūn naturally occurred on the agenda of hadith sources, prophetic biography, and historical works. This agenda was reflected in the treatises as discussions around epidemics, particularly plague, as well as the fight against disease in general in a religious and jurisprudential framework. (ii) Works aimed at diagnosing the plague and dealing with various aspects of it tried to explain disease on the basis of Galenic-Avicennian medicine within the framework of miasma theory, thus deriving their basis from this medical paradigm. (iii) Finally, the encounter with such a brutal illness prompted a quest for all possible remedies, including the occultist culture. This background shaped the language and content of the treatises at different levels. This article first evaluates the modern studies on plague treatises written in the Islamic world. Then, it surveys the Islamic historical sources in order to pin down the meaning they assign to the concepts of wabā’ [epidemic disease] and ṭā‘ūn [plague]. Certain medical works that were the resources for medical doctrines and terminology for plague treatises are also evaluated with a focus on these two concepts. Thus, the aim of this survey is to understand the general conception of epidemic disease and plague in the Islamic world before the Black Death (1346-1353). I discuss and analyze the characteristics of the Ṭā‘ūn literature, which constitutes the main subject of the article and present a database on the literature. While the works from the Mamluk and Ottoman periods constitute a continuous tradition in some respects, Ottoman treatises differ from the Mamluk works in terms of certain features, especially content. Although this study touches on the common aspects of the works from the two periods, it instead analyzes this literature with a focus on points where the two traditions diverge.
XENOBREAST Trial: A prospective study of xenografts establishment from surgical specimens of patients with triple negative or luminal b breast cancer
Authors: Veyssière Hugo , Passildas Judith , Ginzac Angeline , Lusho Sejdi , Bidet Yannick , Molnar Ioana , Bernadach Maureen , Cavaille Mathias , Radosevic-Robin Nina , Durando Xavier
Published: June 2021

Introduction: Patient-derived xenografts (PDX) can be used to explore tumour pathophysiology and could be useful to better understand therapeutic response in breast cancer. PDX from mammary tumours are usually made from metastatic tumours. Thus, PDX from primary mammary tumours or after neoadjuvant treatment are still rare. This study aims to assess the feasibility to establish xenografts from tumour samples of patients with triple negative or luminal B breast cancer in neoadjuvant, adjuvant or metastatic setting.

Methods: XENOBREAST is a single-centre and prospective study. This feasibility pilot trial aims to produce xenografts from tumour samples of patients with triple negative or luminal B breast cancer. Patient enrolment is expected to take 3 years: 85 patients will be enrolled and followed for 28 months. Additional blood samples will be taken as part of the study. Surgical specimens from post-NAC surgery, primary surgery or surgical excision of the metastases will be collected to establish PDX. Histomolecular characteristics of the established PDX will be investigated and compared with the initial histomolecular profile of the collected tumours to ensure that they are well-established.

Ethics and dissemination: XENOBREAST belongs to category 2 interventional research on the human person. This study has been approved by the Sud Méditerranée IV – Montpellier ethics committee. It is conducted notably in accordance with the Declaration of Helsinki and General Data Protection Regulation (GDPR). Study data and findings will be published in peer-reviewed medical journals. We also plan to present the study and all data at national congresses and conferences.

Registration: ClinicalTrials.gov ID NCT04133077; registered on October 21, 2019.