bluuebunny/crossref_metadata_2025 huggingface dataset:
Megakaryocyte TGFβ1 partitions erythropoiesis into immature progenitor/stem cells and maturing precursors
Authors: Di Giandomenico Silvana , Kermani Pouneh , Mollé Nicole , Yabut Maria Mia , Abu-Zeinah Ghaith , Stephens Thomas , Messali Nassima , Schreiner Ryan , Brenet Fabienne , Rafii Shahin , Scandura Joseph M.
Published: June 2020

Erythropoietin (EPO) provides the major survival signal to maturing erythroid precursors (EPs) and is essential for terminal erythropoiesis. Nonetheless, progenitor cells can irreversibly commit to an erythroid fate well before EPO acts, risking inefficiency if these progenitors are unneeded to maintain red blood cell (RBC) counts. We identified a new modular organization of erythropoiesis and, for the first time, demonstrate that the pre-EPO module is coupled to late EPO-dependent erythropoiesis by megakaryocyte (Mk) signals. Disrupting megakaryocytic transforming growth factor β1 (Tgfb1) disorganized hematopoiesis by expanding the pre-EPO pool of progenitor cells and consequently triggering significant apoptosis of EPO-dependent EPs. Similarly, pharmacologic blockade of TGFβ signaling in normal mice boosted the pre-EPO module, leading to apoptosis of EPO-sensitive EPs. Subsequent treatment with low-dose EPO triggered robust RBC production in both models. This work reveals modular regulation of erythropoiesis and offers a new strategy for overcoming chronic anemias.
Gut dysbiosis modulates the immune response to factor VIII in murine hemophilia A
Authors: Tarrant Julie , Cormier Matthew , Nesbitt Kate , Dwyer Courtney , Hough Christine , Lillicrap David
Published: June 2020

The development of neutralizing FVIII antibodies is the most serious complication of hemophilia A treatment. The currently known patient- and treatment-related risk factors for inhibitor development do not accurately predict this adverse event in all patients. The composition of the gut microbiota has been shown to influence immune-mediated diseases at distant anatomical sites (eg, lungs, brain, and joints). We demonstrate that a disrupted gut microbiota can be created in a mouse model of hemophilia A using a broad-spectrum antibiotic. Under controlled conditions, this sustained dysbiosis was associated with an increase in splenic B cells and the development of higher titer, FVIII-specific immunoglobulin G antibodies after FVIII challenge. Splenic and mesenteric lymph node cytokines, T cells, and dendritic cells were unaffected before administration of FVIII. However, the immune transcriptome of both aforementioned secondary lymphoid organs was significantly modified. Short-chain fatty acids (SCFAs), which are immunomodulatory microbial metabolites, were depleted in cecal contents of the dysbiotic mice. Furthermore, supplementation of the drinking water with butyrate, the most immunologically active SCFA, successfully achieved attenuation of the FVIII immune response. Collectively, data from this exploratory study suggest that the composition of the gut microbiota alters the FVIII immune response via the action of specific microbial metabolites on the immune cell transcriptome and that oral supplementation with butyrate effectively reduces the FVIII immune response.
Quality of surgical care can impact survival in patients with bladder cancer after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium
Authors: Ahmed Youssef , Hussein Ahmed A. , May Paul R. , Ahmad Basel , Khan Amir , Benkowski John , Durrani Ayesha , Khan Saira , Kozlowski Justen , Saar Matthias , Wijburg Carl J. , Richstone Lee , Wagner Andrew , Yuh Bertram , Redorta Joan Palou , Dasgupta Prokar , Khan Mohammad Shamim , Menon Mani , Peabody James O. , Hosseini Abolfazl , Gaboardi Franco , Pini Giovannalberto , Schanne Francis , Mottrie Alexandre , Rha Koon-ho , Hemal Ashok , Stockle Michael , Kelly John , Tan Wei Shen , Maatman Thomas J. , Poulakis Vassilis , Kaouk Jihad , Canda Abdullah Erdem , Balbay Mevlana Derya , Wiklund Peter , Guru Khurshid A.
Published: June 2020

Background

Although pathological factors remain the main determinate of survival for patients with bladder cancer, quality of surgical care is crucial for satisfactory outcomes. Using a validated quality score, we investigated the impact of surgical factors on the overall survival (OS), recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with locally advanced and organ-confined disease (OCD). Retrospective review of IRCC database includes 2460 patients from 29 institutions across 11 countries. The final cohort included 1343 patients who underwent RARCs between 2005 and 2016. Patients with locally advanced disease (LAD) (> pT2 and/or N +) were compared with OCD (≤ pT2/N0). Validated Quality Cystectomy Score (QCS) based on four sets of quality metrics was used to compare surgical performance. Kaplan–Meier method was used to compute RFS, CSS and OS rates. Multivariable stepwise logistic regression was used to evaluate variables associated with RFS, DSS and OS.

Results

48% had LAD. When compared to patients with OCD, they received neobladders less frequently (17% vs. 28%, p < 0.001) and experienced higher estimated blood loss (513 vs. 376 ml, p = 0.05). Postoperatively, more patients in the LAD group received adjuvant chemotherapy (24% vs. 4%, p < 0.001) and positive surgical margins (14% vs. 2%, p < 0.001) and had higher 90-day mortality (6% vs. 2%, p < 0.001). On multivariable analysis, female gender, higher QCS score, intracorporeal diversion, pT stage, positive lymph node status and recurrence are considered as predictors of survival. Patients with OCD exhibited better RFS, DSS and OS than patients with LAD. For patients with OCD, higher QCS was associated with improved OS but not RFS or DSS. On the other hand, patients with LAD and higher QCS exhibited higher RFS, DSS and OS when compared to those with lower QCS.

Conclusion

Quality of surgical care can affect disease control and OS in patients with bladder cancer treated with robot-assisted radical cystectomy.
Origin-destination matrix estimation with a conditionally binomial model
Authors: Kuusela Pirkko , Norros Ilkka , Kilpi Jorma , Räty Tomi
Published: June 2020

A doubly stochastic, conditionally binomial model is proposed to describe volumes of vehicular origin-destination flows in regular vehicular traffic, such as morning rush hours. The statistical properties of this model are motivated by the data obtained from inductive loop traffic counts. The model parameters can be expressed as rational functions of the first and second order moments of the observed link counts. Challenges arising from the inaccuracy of moment estimates are studied. A real origin-destination traffic problem of Tampere city is solved by optimisation methods and the accuracy of the solution is examined.
Phylogenomics of expanding uncultured environmental Tenericutes provides insights into their pathogenicity and evolutionary relationship with Bacilli
Authors: Wang Yong , Huang Jiao-Mei , Zhou Ying-Li , Almeida Alexandre , Finn Robert D. , Danchin Antoine , He Li-Sheng
Published: June 2020

Background

The metabolic capacity, stress response and evolution of uncultured environmental Tenericutes have remained elusive, since previous studies have been largely focused on pathogenic species. In this study, we expanded analyses on Tenericutes lineages that inhabit various environments using a collection of 840 genomes.

Results

Several environmental lineages were discovered inhabiting the human gut, ground water, bioreactors and hypersaline lake and spanning the Haloplasmatales and Mycoplasmatales orders. A phylogenomics analysis of Bacilli and Tenericutes genomes revealed that some uncultured Tenericutes are affiliated with novel clades in Bacilli, such as RF39, RFN20 and ML615. Erysipelotrichales and two major gut lineages, RF39 and RFN20, were found to be neighboring clades of Mycoplasmatales. We detected habitat-specific functional patterns between the pathogenic, gut and the environmental Tenericutes, where genes involved in carbohydrate storage, carbon fixation, mutation repair, environmental response and amino acid cleavage are overrepresented in the genomes of environmental lineages, perhaps as a result of environmental adaptation. We hypothesize that the two major gut lineages, namely RF39 and RFN20, are probably acetate and hydrogen producers. Furthermore, deteriorating capacity of bactoprenol synthesis for cell wall peptidoglycan precursors secretion is a potential adaptive strategy employed by these lineages in response to the gut environment.

Conclusions

This study uncovers the characteristic functions of environmental Tenericutes and their relationships with Bacilli, which sheds new light onto the pathogenicity and evolutionary processes of Mycoplasmatales.
Multi-nanolayer drug delivery using radiofrequency plasma technology
Authors: Al Dybiat Iman , Baitukha Alibi , Pimpie Cynthia , Kaci Rachid , Pocard Marc , Arefi Khonsari Farzaneh , Mirshahi Massoud
Published: June 2020

Background

It may be impossible to perform cancer surgery with free margins in the presence of an unresectable structure. Local drug treatment after surgery has been proposed to increase the rate of tumor control.

Methods

Multi-nanolayers (10-330 nm) were generated by a low-pressure (375mTorr) inductively coupled plasma (13.56 MHz) reactor for anticancer drug delivery by the deposition of polycaprolactone-polyethylene glycol multistack barrier on the collagen membrane (100 μm thickness). Carboplatin (300 μg/cm2) was used for the in vitro and in vivo investigations. Energy-dispersive X-ray spectroscopy (15 keV), scanning electron microscopy and inductively coupled plasma mass spectrometry were used to detect the presence of carboplatin in the nanolayer, the tumor sample and the culture medium. Preclinical studies were performed on ovarian (OVCAR-3NIH) and colon (CT26) cancer cell lines as xenografts (45 days) and allografts (23 days) in Swiss-nude (n = 6) and immunocompetent BALB/cByJ mice (n = 24), respectively.

Results

The loading of carboplatin or other drugs between the nanofilm on the collagen membrane did not modify the mesh complex architecture or the drug properties. Drugs were detectable on the membrane for more than 2 weeks in the in vitro analysis and more than 10 days in the in vivo analysis. Cytotoxic mesh decreased cell adherence (down 5.42-fold) and induced cancer cell destruction (up to 7.87-fold). Implantation of the mesh on the mouse tumor nodule modified the cell architecture and decreased the tumor size (50.26%) compared to the control by inducing cell apoptosis.

Conclusion

Plasma technology allows a mesh to be built with multi-nanolayer anticancer drug delivery on collagen membranes.
Childhood injuries and food stamp benefits: an examination of administrative data in one US state
Authors: Heflin Colleen M. , Arteaga Irma , Ndashimye Jean Felix , Rabbitt Matthew P.
Published: June 2020

Background

Currently in the United States, childhood injuries are the leading cause of mortality and morbidity, resulting in an estimated 9.2 million emergency department visits and $17 billion annually in medical costs. For preschoolers, it is also the leading cause of disability.

Methods

We use linked administrative data for SNAP and Medicaid in Missouri from January 2010 to December 2013 to explore monthly patterns in the association between SNAP receipt and ER claims due to childhood injury for children age 0–5 and to examine if these patterns are sensitive to the timing of SNAP benefits. We chose the state of Missouri because unlike most states that disburse SNAP benefits within the first 10 days of the calendar month, Missouri pays SNAP benefits between the first twenty-two days of the month, based on the recipient’s birthdate and last name.

Results

SNAP benefits received later in the calendar month are associated with reductions in ER claims for childhood injuries. Furthermore, the final week in the SNAP benefit month is associated with an increase in ER claims for childhood injuries.

Conclusion

In terms of public policy, our results suggest that having SNAP disbursement later in the month may have benefits for households.
PCNL in COPD patient in the sit position under local infiltration anesthesia case report
Authors: Zhai Jianpo , Wang Hai , Xu Xiao , Liu Zhenhua , Man Libo
Published: June 2020

Background

Percutaneous nephrolithotomy is traditionally performed in the prone or supine position. We report the first case of percutaneous nephrolithotomy in sit position under local infiltration anesthesia.

Case summary

A 69-year-old male presented with left flank pain. Kidney B ultrasound and computed tomography scan showed multiple left renal calculi and hydronephrosis. He had a long history of chronic obstructive pulmonary disease, with severe ventilatory and cardiac dysfunction, and cannot tolerate the prone or supine position. The patient received the surgery in sit position under local infiltration anesthesia. The operative time was 1 h. The visual analogue scale score during the surgery was 3. The patient had no intraoperative and postoperative complications. The postoperative plain radiography showed no residual stone fragments.

Conclusions

We believe that in high-risk patients who need to undergo PCNL, a combination of sit position and local infiltration anesthesia is an alternative method.
The disease stage-associated imbalance of Th1/Th2 and Th17/Treg in uterine cervical cancer patients and their recovery with the reduction of tumor burden
Authors: Lin Wei , Zhang Hua-ling , Niu Zhao-yuan , Wang Zhen , Kong Yan , Yang Xing-sheng , Yuan Fang
Published: June 2020

Background

Nearly all uterine cervical cancer (UCC) cases result from human papillomavirus (HPV) infection. After high-risk HPV infection, most HPV infections are naturally cleared by humoral and cell-mediated immune responses. Thus, cervical lesions of only few patients progress into cervical cancer via cervical intraepithelial neoplasia (CIN) and lead to persistent oncogenic HPV infection. This suggests that immunoregulation plays an instrumental role in the carcinogenesis. However, there was a few studies on the relation between the immunologic dissonance and clinical characteristics of UCC patients.

Method

We examined the related immune cells (Th1, Th2, Th17, and Treg cells) by flow cytometric analysis and analyzed their relations with UCC stages, tumor size, differentiation, histology type, lymph node metastases, and vasoinvasion. Next, we quantified the Th1, Th2, Th17, and Treg cells before and after the operation both in UCC and CIN patients.

Results

When compared with stage I patients, decreased levels of circulating Th1 cells and elevated levels of Th2, Th17, and Treg cells were detected in stage II patients. In addition, the imbalance of Th1/Th2 and Th17/Treg cells was related to the tumor size, lymph node metastases, and vasoinvasion. We found that immunological cell levels normalized after the operations. In general, immunological cell levels in CIN patients normalized sooner than in UCC patients.

Conclusions

Our findings suggested that peripheral immunological cell levels reflect the patient’s condition.
Intimate partner violence as a factor in contraceptive discontinuation among sexually active married women in Nigeria
Authors: KUPOLUYI Joseph Ayodeji
Published: June 2020

Background

In spite of the well-established associations between socioeconomic and demographic factors and the high rate of contraceptive discontinuation among sexually active married contraceptive users, little is known in Nigeria about the relationship between contraceptive discontinuation and sexually active married women who have experienced Intimate Partner Violence (IPV).

Methods

The 2013 Nigeria Demographic and Health Survey data on women’s reproductive calendars and domestic violence were used to investigate the relationship between IPV and contraceptive discontinuation in a year period. A weighted sample size of 1341 women in a union in the domestic violence module, who have experienced IPV, and are using any contraceptive and are not sterilized in the 12 months periods was analyzed using frequency tables and chart, Pearson’s chi-square test, and binary logistic regression model.

Results

The results showed that women who have experienced any type of IPV are 1.28 times more likely to have discontinued contraceptive use although they are still at risk of becoming pregnant (aOR = 1.28, CI: 1.15–1.91; p < 0.05) than those who have not experienced IPV. The tertiary level of education (aOR = 3.94, CI = 1.67–9.29; p < 0.05), unemployed status (aOR = 1.97, CI = 1.07–3.62; p < 0.05), and higher marital duration of 20 years and above (aOR = 4.89, CI = 2.26–10.57; p < 0.05) significantly influenced women who have experienced any types of IPV to discontinue contraceptives even though they are still at risk of becoming pregnant than those who have not experienced IPV.

Conclusion

The study revealed that women who have experienced any form of IPV were significantly influenced by their education, occupation, the number of living children, and marital duration to discontinue contraception while still at risk of becoming pregnant. Thus, the study concludes that intervention programmes aimed at increasing contraceptive prevalence rate should be mindful of IPV which may affect women’s use of contraceptives.
Intimate partner violence and nutritional status among nepalese women: an investigation of associations
Authors: Adhikari Ramesh P. , Yogi Subash , Acharya Ajay , Cunningham Kenda
Published: June 2020

Background

Malnutrition among women in Nepal persists as a major public health burden. Global literature suggests that domestic violence may have a negative impact on women’s nutritional status. The contribution of intimate partner violence (IPV) to increased stress levels, poor self-care including the consumption of less food and, in turn, malnutrition has been documented. However, there is little empirical evidence on IPV and its relationship with women’s nutritional status in Nepal and thus, this paper assesses these associations.

Methods

We used data on non-pregnant married women (n = 3293) from the 2016 Nepal Demographic and Health Survey (NDHS). The primary exposure variable was whether the women had ever experienced physical, sexual, or emotional violence or controlling behaviours by a current or former partner, based on her responses to the NDHS domestic violence questions. The primary outcome variables were three indicators of malnutrition: under-weight (BMI < 18.5), over-weight (BMI > 25), and anemia (Hb < 11.0 g dL). We used logistic and multinomial regression models, adjusted for potential socio-demographic and economic confounders, as well as clustering, to examine associations between IPV exposure and malnutrition.

Results

Approximately 44% of women had experienced at least one of the four types of IPV. Among them, around 16, 25%. and 44% were underweight, overweight, or anemic, respectively, compared to 13, 29, and 35% of women never exposed to IPV. We did not find any associations between underweight and any of the four types of IPV. Overweight was associated with physical violence (adjusted RRR = 0.67, P < 0.01, CI = 0.50–0.88) and severe physical violence (adjusted RRR = 0.53, P < 0.05, CI = 0.32–0.88) Controlling behaviors were associated with anemia (adjusted RRR = 1.31, P < 0.01, CI = 1.11–1.54).

Conclusions

Among married Nepalese women, physical violence appears to be a risk factor for one’s weight and controlling behaviors for one’s anemia status. Additional, rigorous, mixed-methods research is needed to understand the reporting of IPV and what relationships do or do not exist between IPV experience and nutrition both in Nepal and in other settings.
Identifying essential proteins in dynamic protein networks based on an improved h-index algorithm
Authors: Dai Caiyan , He Ju , Hu Kongfa , Ding Youwei
Published: June 2020

Background

The essential proteins in protein networks play an important role in complex cellular functions and in protein evolution. Therefore, the identification of essential proteins in a network can help to explain the structure, function, and dynamics of basic cellular networks. The existing dynamic protein networks regard the protein components as the same at all time points; however, the role of proteins can vary over time.

Methods

To improve the accuracy of identifying essential proteins, an improved h-index algorithm based on the attenuation coefficient method is proposed in this paper. This method incorporates previously neglected node information to improve the accuracy of the essential protein search. Based on choosing the appropriate attenuation coefficient, the values, such as monotonicity, SN, SP, PPV and NPV of different essential protein search algorithms are tested.

Results

The experimental results show that, the algorithm proposed in this paper can ensure the accuracy of the found proteins while identifying more essential proteins.

Conclusions

The described experiments show that this method is more effective than other similar methods in identifying essential proteins in dynamic protein networks. This study can better explain the mechanism of life activities and provide theoretical basis for the research and development of targeted drugs.
METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer
Authors: Chen Xiaoxiang , Xu Mu , Xu Xueni , Zeng Kaixuan , Liu Xiangxiang , Pan Bei , Li Chenmeng , Sun Li , Qin Jian , Xu Tao , He Bangshun , Pan Yuqin , Sun Huilin , Wang Shukui
Published: June 2020

Background

Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide, and its main cause of death is distant metastasis. Methyltransferase-like 14(METTL14), a major RNA N6-adenosine methyltransferase, is involved in tumor progression via regulating RNA function. The goal of the study is to uncover the biological function and molecular mechanism of METTL14 in CRC.

Methods

Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) assays were employed to detect METTL14 and SOX4 in CRC cell lines and tissues. The biological functions of METTL14 were demonstrated using in vitro and in vivo experiments. Chromatin immunoprecipitation (ChIP), Transcrptomic RNA sequencing (RNA-Seq), m6A-RNA immunoprecipitation sequencing (MeRIP-Seq), RNA immunoprecipitation and luciferase reporter assays were used to explore the mechanism of METTL14 action.

Results

METTL14 expression was significantly downregulated in CRC and decreased METTL14 was associated with poor overall survival (OS). Both the univariate and multivariate Cox regression analysis indicated that METTL14 was an independent prognostic factor in CRC. Moreover, lysine-specific histone demethylase 5C(KDM5C)-mediated demethylation of histone H3 lysine 4 tri-methylation(H3K4me3) in the promoter of METTL14 inhibited METTL14 transcription. Functionally, we verified that METTL14 inhibited CRC cells migration, invasion and metastasis through in vitro and in vivo assays, respectively. Furthermore, we identified SRY-related high-mobility-group box 4(SOX4) as a target of METTL14-mediated m6A modification. Knockdown of METTL14 markedly abolished SOX4 mRNA m6A modification and elevated SOX4 mRNA expression. We also revealed that METTL14-mediated SOX4 mRNA degradation relied on the YTHDF2-dependent pathway. Lastly, we demonstrated that METTL14 might inhibit CRC malignant process partly through SOX4-mediated EMT process and PI3K/Akt signals.

Conclusions

Decreased METTL14 facilitates tumor metastasis in CRC, suggesting that METTL14 might be a potential prognostic biomarker and effective therapeutic target for CRC.

Graphical abstract
Quality of life among patients with cardiac disease: the impact of comorbid depression
Authors: Bahall Mandreker , Legall George , Khan Katija
Published: June 2020

Background

Patients with cardiac disease with or without depression may also have major physical and mental problems. This study assesses and compares the quality of life (QOL) of patients with cardiac disease with and without depression and accompanying comorbidities.

Methods

A cross-sectional study was conducted with a convenience sample of 388 patients with cardiac disease. The 12-item Short-Form (SF-12)-patient was used to measure physical component scale (PCS) and mental component scale (MCS) QOL, and the Patient Health Questionnaire (PHQ-9) was used to measure depression. The Charlson Comorbidity Index was used to estimate 10-year survival probability. Descriptive statistics, analysis of covariance (ANCOVA), chi-square tests, and binary logistic regression were used for analysis.

Results

The prevalence of minimal to mild depression was 65.7% [(95% CI (60.8, 70.4)] and that of moderate to severe depression was 34.3% [95% CI (29.6, 39.2)]. There was no significant association between the level of PHQ-categorised depression and age (p = 0.171), sex (p = 0.079), or ethnicity (p = 0.407). The overall mean PCS and MCS QOL was 32.5 [95% CI (24.4, 40.64)] and 45.4 [95% CI (44.4, 46.4)], respectively, with no significant correlation between PCS and MCS [r (Pearson’s) = 0.011; p = 0.830)]. There were QOL differences among the five PHQ categories (PCS: p = 0.028; MCS: p ≤ 0.001) with both MCS and PCS decreasing with increasing depression. ANCOVA (with number of comorbidities as the covariate) showed a significant age × ethnicity interaction for PCS (p = 0.044) and MCS (p = 0.039), respectively. Young Indo-Trinidadians had significantly lower PCS than did Afro-Trinidadians, while the converse was true for MCS. Depression, age, and number of comorbidities were predictors of PCS, while depression, age, and sex were predictors of MCS.

Conclusions

Increasing severity of depression worsened both PCS and MCS QOL. Age and level of clinical depression predicted QOL, with number of comorbidities predicting only PCS and sex predicting only MCS. Efforts must be made to treat depression in all age groups of patients with cardiac disease.
Correction to: SNCG promotes the progression and metastasis of high-grade serous ovarian cancer via targeting the PI3K/AKT signaling pathway
Authors: Zhang Jing , Liu Xiao-han , Li Cong , Wu Xiao-xing , Chen Yan-lin , Li Wen-wen , Li Xian , Gong Fan , Tang Qin , Jiang Dan
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Acupuncture for primary fibromyalgia: Study protocol of a randomized controlled trial
Authors: Han Man , Cui Jiakang , Xiao Yuya , Xiao Donghong , Jiao Juan , Peng Qiuwei , Tian Feng , Tang Xiaopo , Zhang Jianyong , Jiang Quan
Published: June 2020

Background

Acupuncture is well recognized for its unique therapeutic effect for many diseases as a nonpharmacological therapy in traditional Chinese medicine (TCM). However, whether acupuncture can effectively treat fibromyalgia is currently unclear. Therefore, we aim to design a study protocol of a randomized controlled clinical trial and assess the effectiveness of acupuncture for patients with fibromyalgia, which may lead to alleviation of clinical symptoms and improvement of patients’ quality of life.

Methods

The study is designed as a randomized, blinded, placebo-controlled trial of two cohorts conducted at Guang’anmen Hospital of China Academy of Chinese Medical Sciences and Shenzhen Traditional Chinese Medicine Hospital, respectively. A total of 68 patients with primary fibromyalgia, diagnosed with the American College of Rheumatology criteria, are randomly allocated with a 1:1 ratio to acupuncture or sham acupuncture groups. All subjects will receive acupuncture intervention for 8 weeks with follow-up assessments every 4 weeks for 16 weeks. The primary outcome will be evaluated using the visual analogue scale (VAS) and revised fibromyalgia impact questionnaire (FIQR) for pain intensity. The secondary outcome measures will include: Multidimensional Assessment of Fatigue scale (MAF), Short Form-36 (SF-36), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), Chinese perceived stress scales (pss-14), changes in the number of 18 tender points, patient satisfaction for the treatment and adverse events. The mentioned outcome measurements will be assessed every 4 weeks for 6 months.

Discussion

This clinical trial will use advanced research methods to evaluate the efficacy and safety of acupuncture on fibromyalgia. The results of this trial may provide clinical evidence on the beneficial effects of acupuncture in treating fibromyalgia.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800016826: AMCTR-IOR-18000184. Registered 27 June 2018, http://www.acmctr.org/listbycreater.aspx
Influence of sampling schedules on [177Lu]Lu-PSMA dosimetry
Authors: Rinscheid Andreas , Kletting Peter , Eiber Matthias , Beer Ambros J. , Glatting Gerhard
Published: June 2020

Background

Individualized dosimetry is recommended for [177Lu]Lu-PSMA radioligand therapy (RLT) which is resource-intensive and protocols are often not optimized. Therefore, a simulation study was performed focusing on the determination of efficient optimal sampling schedules (OSS) for renal and tumour dosimetry by investigating different numbers of time points (TPs).

Methods

Sampling schedules with 1–4 TPs were investigated. Time-activity curves of the kidneys and two tumour lesions were generated based on a physiologically based pharmacokinetic (PBPK) model and biokinetic data of 13 patients who have undergone [177Lu]Lu-PSMA I&T therapy. Systematic and stochastic noise of different ratios was considered when modelling time-activity data sets. Time-integrated activity coefficients (TIACs) were estimated by simulating the hybrid planar/SPECT method for schedules comprising at least two TPs. TIACs based on one single SPECT/CT measurement were estimated using an approximation for reducing the number of fitted parameters. For each sampling schedule, the root-mean-squared error (RMSE) of the deviations of the simulated TIACs from the ground truths for 1000 replications was used as a measure for accuracy and precision.

Results

All determined OSS included a late measurement at 192 h p.i., which was necessary for accurate and precise tumour TIACs. OSS with three TPs were identified to be 3–4, 96–100 and 192 h with an additional SPECT/CT measurement at the penultimate TP. Kidney and tumour RMSE of 6.4 to 7.7% and 6.3 to 7.8% were obtained, respectively. Shortening the total time for dosimetry to e.g. 96 h resulted in kidney and tumour RMSE of 6.8 to 8.3% and 9.1 to 11%, respectively. OSS with four TPs showed similar results as with three TPs. Planar images at 4 and 68 h and a SPECT/CT shortly after the 68 h measurement led to kidney and tumour RMSE of 8.4 to 12% and 12 to 16%, respectively. One single SPECT/CT measurement at 52 h yielded good approximations for the kidney TIACs (RMSE of 7.0%), but led to biased tumour TIACs.

Conclusion

OSS allow improvements in accuracy and precision of renal and tumour dosimetry for [177Lu]Lu-PSMA therapy with potentially less effort. A late TP is important regarding accurate tumour TIACs.
The impact of the Trauma Triage App on pre-hospital trauma triage: design and protocol of the stepped-wedge, cluster-randomized TESLA trial
Authors: van der Sluijs Rogier , Fiddelers Audrey A. A. , Waalwijk Job F. , Reitsma Johannes B. , Dirx Miranda J. , den Hartog Dennis , Evers Silvia M. A. A. , Goslings J. Carel , Hoogeveen W. Margreet , Lansink Koen W. , Leenen Luke P. H. , van Heijl Mark , Poeze Martijn
Published: June 2020

Background

Field triage of trauma patients is crucial to get the right patient to the right hospital within a particular time frame. Minimization of undertriage, overtriage, and interhospital transfer rates could substantially reduce mortality rates, life-long disabilities, and costs. Identification of patients in need of specialized trauma care is predominantly based on the judgment of Emergency Medical Services professionals and a pre-hospital triage protocol. The Trauma Triage App is a smartphone application that includes a prediction model to aid Emergency Medical Services professionals in the identification of patients in need of specialized trauma care. The aim of this trial is to assess the impact of this new digital approach to field triage on the primary endpoint undertriage.

Methods

The Trauma triage using Supervised Learning Algorithms (TESLA) trial is a stepped-wedge cluster-randomized controlled trial with eight clusters defined as Emergency Medical Services regions. These clusters are an integral part of five inclusive trauma regions. Injured patients, evaluated on-scene by an Emergency Medical Services professional, suspected of moderate to severe injuries, will be assessed for eligibility. This unidirectional crossover trial will start with a baseline period in which the default pre-hospital triage protocol is used, after which all clusters gradually implement the Trauma Triage App as an add-on to the existing triage protocol. The primary endpoint is undertriage on patient and cluster level and is defined as the transportation of a severely injured patient (Injury Severity Score ≥ 16) to a lower-level trauma center. Secondary endpoints include overtriage, hospital resource use, and a cost-utility analysis.

Discussion

The TESLA trial will assess the impact of the Trauma Triage App in clinical practice. This novel approach to field triage will give new and previously undiscovered insights into several isolated components of the diagnostic strategy to get the right trauma patient to the right hospital. The stepped-wedge design allows for within and between cluster comparisons.

Trial registration

Netherlands Trial Register, NTR7243. Registered 30 May 2018, https://www.trialregister.nl/trial/7038.
Papillary tumour of the pineal region: a case report
Authors: Bromfield Michael , Profyris Christos , Mehtar Aadila , Du Toit Marna , Wadee Reubina
Published: June 2020

Background

Papillary tumor of the pineal region is an unusual, recently described entity with potential for misinterpretation as either an ependymoma or choroid plexus papilloma. With few reported cases, there is little data regarding the biologic behavior, natural course and optimal treatment for these patients. Further accumulation of reports will assist with defining this entity and may provide further insight into management of such patients.

Case presentation

This patient was a 24-year-old male with new onset seizures and a decreased level of consciousness. MRI scan showed a large heterogeneously enhancing solid-cystic mass in the pineal region extending to the third ventricle.

Discussion

Papillary tumor of the pineal region is a neuroepithelial tumor with distinct morphological and immunohistochemical features that can be utilized to help differentiate it from other primary and metastatic tumors occurring within this region. Although there is currently no clear consensus, the potential for disease progression and CSF dissemination supports early aggressive therapy in these patients.
Ultrastructure of the fertilized egg envelopes in Ancistrus cirrhosus, Loricariidae, Teleostei
Authors: Kim Dong Heui
Published: June 2020

We examined the morphology of fertilized egg and ultrastructures of fertilized egg envelopes of Ancistrus cirrhosus belong to Loricariidae using light and electron microscopes. The fertilized eggs formed a mass on the spawning place and were yellowish, spherical, non-transparent, demersal, adhesive, and a narrow perivitelline space. But, the adhesiveness of fertilized eggs was disappeared after spawning excluding contact parts. The micropyle with funnel shape was surrounded by 15–19 furrow lines of egg envelope in a spoke-like pattern. The outer surface of egg envelope has smooth side and inner surface of egg envelope was rough with grooves. Also, the total thickness of the fertilized egg envelope was about 32.58 ± 0.85 μm (n = 20), and the fertilized egg envelope consisted of three layers, an outer adhesive electron-dense layer, a middle layer with low electron density and an inner electron-dense layer with grooves in counter structure from other most teleost. Collectively, these morphological characteristics and adhesive property of fertilized egg, and ultrastructures of micropyle, outer surface, and section of fertilized egg envelope are showed species specificity.
Successful Outcomes of Newly Diagnosed T Lymphoblastic Lymphoma: Results From Children’s Oncology Group AALL0434
Authors: Hayashi Robert J. , Winter Stuart S. , Dunsmore Kimberly P. , Devidas Meenakshi , Chen Zhiguo , Wood Brent L. , Hermiston Michelle L. , Teachey David T. , Perkins Sherrie L. , Miles Rodney R. , Raetz Elizabeth A. , Loh Mignon L. , Winick Naomi J. , Carroll William L. , Hunger Stephen P. , Lim Megan S. , Gross Thomas G. , Bollard Catherine M.
Published: June 2020

PURPOSE

The Children’s Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multi-agent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients.

PATIENTS AND METHODS

The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≥ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≥ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible.

RESULTS

At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups ( P = .29) or by treatment regimen ( P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients.

CONCLUSION

COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.
Biomimetic device and foreign body reaction cooperate for efficient tumour cell capture in murine advanced ovarian cancer
Authors: Alonso-Alconada Lorena , de la Fuente Alexandre , Santacana María , Ferreiros Alba , Lopez-Lopez Rafael , Matias-Guiu Xavier , Abal Miguel
Published: June 2020

Metastasis is facilitated by the formation of pre-metastatic niches through the remodelling of the extracellular matrix (ECM) promoted by haematopoietic and stromal cells. The impact of these primed sites is pronounced for intraperitoneal metastases, where the cavity-exposed ECM supports the attachment of the disseminating tumour cells. Likewise, implantation of biomaterial scaffolds influences metastatic progression systemically through a foreign body reaction (FBR). In this study, we integrated the concept of creating an artificial niche to capture tumour cells actively disseminating in the peritoneal cavity with a therapeutic strategy modulating the interactions of metastatic cells with the ECM. The aim was to transform a disseminated disease into a focal disease. For this, we designed and developed a ‘biomimetic’ ECM composed of a nonresorbable three-dimensional scaffold with collagen coating and characterized the FBR to the implanted biomaterial. We also analysed the safety of the implanted devices and their ability to capture tumour cells in different murine preclinical models of advanced ovarian cancer. Implantation of the biomimetic devices resulted in an initial inflammatory reaction that transformed progressively into a fibrous connective tissue response. The adhesive capabilities of the scaffold were improved with the ancillary effect of the FBR and showed clinical utility in terms of the efficacy of capture of tumour cells, disease focalization and survival benefit. These results demonstrated the performance and safety of this ‘biomimetic’ ECM in preclinical models of advanced ovarian cancer. Translated into the clinical setting, this new therapeutic strategy represents the possibility for control of peritoneal carcinomatosis upon primary ovarian debulking surgery and to expand the percentage of patients who are candidates for second rescue surgeries at the time of relapse.
Internal replication of computational workflows in scientific research
Authors: Benjamin-Chung Jade , Colford, Jr. John M. , Mertens Andrew , Hubbard Alan E. , Arnold Benjamin F.
Published: June 2020

Failures to reproduce research findings across scientific disciplines from psychology to physics have garnered increasing attention in recent years. External replication of published findings by outside investigators has emerged as a method to detect errors and bias in the published literature. However, some studies influence policy and practice before external replication efforts can confirm or challenge the original contributions. Uncovering and resolving errors before publication would increase the efficiency of the scientific process by increasing the accuracy of published evidence. Here we summarize the rationale and best practices for internal replication, a process in which multiple independent data analysts replicate an analysis and correct errors prior to publication. We explain how internal replication should reduce errors and bias that arise during data analyses and argue that it will be most effective when coupled with pre-specified hypotheses and analysis plans and performed with data analysts masked to experimental group assignments. By improving the reproducibility of published evidence, internal replication should contribute to more rapid scientific advances.
Community of Aquatic Macroinvertebrates in an Atlantic Forest Stream, Brazil
Authors: Azevedo Rafael Santos de , Dumas Leandro , Rodrigues Daniela , Rezende Carla Ferreira , Caramaschi Érica Pellegrini , Mazzoni Rosana , Nessimian Jorge
Published: June 2020

Composition, diversity and density of benthic macroinvertebrates were described based on samples from the four different sites of Rio Mato Grosso, Saquarema, Rio de Janeiro. Biotic and environmental data were obtained in January 2006 in microhabitats with different substrates. A total of 5.605 specimens of the 28 insect families and two crustaceous families are sampled. The lowest values of richness, diversity, equitability and density were observed in low altitude sites. The highest diversity and density values were observed in litter substrate, while sand substrate showed lower values of these parameters.

Estrutura da Comunidade de Macroinvertebrados Aquáticos de um Riacho de Mata Atlântica, Brasil

Resumo. A composição, diversidade e densidade de macroinvertebrados bentônicos foram descritas a partir de amostras provenientes de quatro localidades distintas do Rio Mato Grosso, Saquarema, Rio de Janeiro. Os dados bióticos e abióticos foram obtidos em janeiro 2006 em microhabitats com diferentes tipos de substrato. Foi amostrado um total de 5.605 espécimes de 28 famílias de insetos e duas de crustáceos. Os menores valores de riqueza, diversidade, equitabilidade e densidade foram registrados nas localidades de menor altitude. Folhiço foi o substrato com maiores valores de diversidade e densidade, enquanto areia apresentou os menores valores desses parâmetros.
Fauna de Coleoptera Associada a Carcaças de Coelhos Expostas em uma Área Urbana no Sul do Brasil
Authors: Silva Richard Cordeiro da , Santos Wellington Emanuel dos
Published: June 2020

Estudo da fauna de Coleoptera associada a carcaças de coelhos, Oryctolagus cuniculus Linnaeus (Lagomorpha, Leporidae), durante o verão de 2010 e o inverno de 2011, em uma área urbana do norte do Paraná, sul do Brasil, é apresentado. Para captura dos coleópteros foram utilizadas armadilhas do tipo bandeja, pitfall e Shannon modificada. Foram coletados 236 coleópteros pertencentes a 12 famílias e pelo menos 25 espécies. Staphylinidae (52,5%) e Histeridae (26,7%) foram as famílias mais abundantes em ambas as estações, representadas principalmente por Aleochara bonariensis Lynch e Euspilotus “grupo” azureus sp., respectivamente. Entre as estações, tanto a decomposição das carcaças quanto a sucessão da coleopterofauna de interesse forense ocorreram de forma distinta, devido à variação expressiva dos fatores abióticos. Durante o inverno, a maioria dos indivíduos de Euspilotus "grupo" azureus sp. (96,8%) foi capturada no estágio de Putrefação Escura, revelando uma associação a esse estágio. Apesar da sazonalidade do ambiente, não houve diferença significativa da abundância dos coleópteros mais coletados, nem da coleopterofauna em geral, entre as estações.

Coleoptera Fauna Associated with Rabbit Carcasses Exposed in an Urban Area in Southern Brazil

Abstract. Study of Coleoptera fauna associated with rabbit carcasses, Oryctolagus cuniculus Linnaeus (Lagomorpha, Leporidae), during the summer of 2010 and winter of 2011, is present at an urban area of Northern Paraná State, Southern Brazil. To capture the beetles were used pan, pitfall and modified Shannon traps. We collected 236 beetles belonging to 12 families and at least 25 species. Staphylinidae (52.5%) and Histeridae (26.7%) were the most abundant families in both seasons represented mainly by Aleochara bonariensis Lynch and Euspilotus "group" azureus sp., respectively. Among the seasons, both the decomposition of the carcasses and the succession of coleopterofauna of forensic interest occurred differently due to significant variation of abiotic factors. During the winter, most individuals of Euspilotus "group" azureus sp. (96.8%) was captured at the stage of Black Putrefaction, showing an association at this stage. Despite the environment seasonality, there wasn’t significant difference of the abundance among seasons by main beetles neither by coleopterofauna.
Young people's experiences of an anti-bullying Drama in Education workshop six months' post-participation
Authors: Mitchell Aby
Published: June 2020

The purpose of this primary research study was to explore young people's experiences of an anti-bullying Drama in Education workshop, to understand the meanings young people have attributed to their experiences in relation to the workshop using an interpretative study design and to understand if the intervention has influenced participant's knowledge, skills, and behaviours in bullying situations. The research aims to fill the knowledge gap of the mechanisms in which arts and health promotion and health education interventions enhance social and cognitive skills in young people and the longitudinal impact of drama interventions and their relevance in enhancing long-term skills and knowledge.