bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric testing of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group—Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy
Authors: Cheng Hui Lin , Lopez Violeta , Lam Simon Ching , Leung Anthony Kwun To , Li Yu Chung , Wong Kam Hung , Au Joseph Siu Kie , Sundar Raghav , Chan Alexandre , De Ng Terrence Rong , Suen Lorna Kwai Ping , Chan Choi Wan , Yorke Janelle , Molassiotis Alex
Published: July 2020

Background

The aim of this study was to evaluate the psychometric properties of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group—Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy.

Methods

Patients were assessed with the FACT/GOG-Ntx subscale, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Scale 20 (EORTC QLQ-CIPN20), National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE), and light touch test using 10 g monofilament for up to ten assessment points from baseline (prior to initiation of first chemotherapy), after the end of each cycle (up to 6 cycles, 3 weeks per cycle), and at 6, 9, and 12 months after starting chemotherapy. Psychometric analyses included internal consistency reliability, convergent validity, factorial validity, sensitivity to change and responsiveness (minimal clinically important difference, MCID).

Results

Cronbach’s alpha coefficients of the FACT/GOG-Ntx subscale were 0.82–0.89 across assessment points. The subscale strongly correlated with the EORTC QLQ-CIPN20 (r = 0.79–0.93) but low-to-moderately correlated with the NCI-CTCAE sensory (rs = 0.23–0.45) and motor items (rs = 0.15–0.50) as well as the monofilament test (rs = 0.23–0.47). The hypothesized 4-factor structure of the FACT/GOG-Ntx subscale was not confirmed at assessment points (χ2/df = 2.26–8.50; all P < 0.001). The subscale exhibited small-to-moderate sensitivity to change (r = 0.17–0.37). The MCIDs were between 1.38 and 3.68.

Conclusion

The FACT/GOG-Ntx subscale has satisfactory reliability, validity, sensitivity to change and responsiveness to evaluate CIPN in cancer patients. Future research is needed to explore the factorial structure of the FACT/GOG-Ntx subscale as the published four-factor structure was not supported in this study.
Psychometric evaluation of Azeri version of the head and neck cancer specific quality of life questionnaire (EORTC QLQ-H&N43)
Authors: Davudov Mahammad M. , Rahimov Chingiz , Harirchi Iraj , Mirzajani Zoheir , Amiraliyev Namig , Amiraliyev Kanan , Rustamova Narmin , Zebardast Jayran , Montazeri Ali
Published: July 2020

Background

Oral cancer surgery can have a deep effect on the quality of life in the patient both in terms of functional and psychological aspects. This study aimed to translate and validate the European Organization for Research and Treatment of Cancer head and neck cancer specific quality of life questionnaire (EORTC QLQ-H&N43) in Azerbaijan.

Methods

Forward-backward translation was applied in order to translate the EORTC QLQ-H&N43 from English into Azeri. Then, a sample of patients with oral cancer attending a teaching hospital affiliated to Azerbaijan Medical University completed the EORTC QLQ-C30 (the core cancer specific questionnaire), and the EORTC QLQ-H&N43. To evaluate psychometric properties of the QLQ-H&N43, known groups validity, convergent and divergent validity was performed. Internal consistency reliability was examined by estimating the Crornbach’s alpha coefficient.

Results

Ninety-six patients with confirmed diagnosis of oral cancer were entered into the study. The mean age of patients was 59.6 (SD = 10.7) years and 36 patients (37.5%) diagnosed as having stage IV and 10 patients (10.5%) were metastatic. The results obtained from comparing quality of life scores among these patients showed that the questionnaire was able to differentiate among patients who differed in stage and metastasis lending support to its validity. In addition convergent and divergent validity showed satisfactory results. The internal consistency of the multi-item scales as assessed by the Cronbach’s alpha coefficient showed acceptable results (alpha ranging from 0.66 to 0.78).

Conclusion

The findings suggest that in general the Azeri version of EORTC QLQ-H&N43 has satisfactory internal consistency reliability and validity, but additional psychometric evaluation is needed to draw firm conclusions.
Correlates of physical activity behavior in adults: a data mining approach
Authors: Farrahi Vahid , Niemelä Maisa , Kärmeniemi Mikko , Puhakka Soile , Kangas Maarit , Korpelainen Raija , Jämsä Timo
Published: July 2020

Purpose

A data mining approach was applied to establish a multilevel hierarchy predicting physical activity (PA) behavior, and to methodologically identify the correlates of PA behavior.

Methods

Cross-sectional data from the population-based Northern Finland Birth Cohort 1966 study, collected in the most recent follow-up at age 46, were used to create a hierarchy using the chi-square automatic interaction detection (CHAID) decision tree technique for predicting PA behavior. PA behavior is defined as active or inactive based on machine-learned activity profiles, which were previously created through a multidimensional (clustering) approach on continuous accelerometer-measured activity intensities in one week. The input variables (predictors) used for decision tree fitting consisted of individual, demographical, psychological, behavioral, environmental, and physical factors. Using generalized linear mixed models, we also analyzed how factors emerging from the model were associated with three PA metrics, including daily time (minutes per day) in sedentary (SED), light PA (LPA), and moderate-to-vigorous PA (MVPA), to assure the relative importance of methodologically identified factors.

Results

Of the 4582 participants with valid accelerometer data at the latest follow-up, 2701 and 1881 had active and inactive profiles, respectively. We used a total of 168 factors as input variables to classify these two PA behaviors. Out of these 168 factors, the decision tree selected 36 factors of different domains from which 54 subgroups of participants were formed. The emerging factors from the model explained minutes per day in SED, LPA, and/or MVPA, including body fat percentage (SED: B = 26.5, LPA: B = − 16.1, and MVPA: B = − 11.7), normalized heart rate recovery 60 s after exercise (SED: B = -16.1, LPA: B = 9.9, and MVPA: B = 9.6), average weekday total sitting time (SED: B = 34.1, LPA: B = -25.3, and MVPA: B = -5.8), and extravagance score (SED: B = 6.3 and LPA: B = − 3.7).

Conclusions

Using data mining, we established a data-driven model composed of 36 different factors of relative importance from empirical data. This model may be used to identify subgroups for multilevel intervention allocation and design. Additionally, this study methodologically discovered an extensive set of factors that can be a basis for additional hypothesis testing in PA correlates research.
The glycosyltransferase EXTL2 promotes proteoglycan deposition and injurious neuroinflammation following demyelination
Authors: Pu Annie , Mishra Manoj K. , Dong Yifei , Ghorbanigazar Samira , Stephenson Erin L. , Rawji Khalil S. , Silva Claudia , Kitagawa Hiroshi , Sawcer Stephen , Yong V. Wee
Published: July 2020

Background

Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of axonal regrowth and remyelination. More recently, they have also been highlighted as a modulator of macrophage infiltration into the central nervous system in experimental autoimmune encephalomyelitis, an inflammatory model of multiple sclerosis.

Methods

We interrogated results from single nucleotide polymorphisms (SNPs) lying in or close to genes regulating CSPG metabolism in the summary results from two publicly available systematic studies of multiple sclerosis (MS) genetics. A demyelinating injury model in the spinal cord of exostosin-like 2 deficient  (EXTL2-/-) mice was used to investigate the effects of dysregulation of EXTL2 on remyelination. Cell cultures of bone marrow-derived macrophages and primary oligodendrocyte precursor cells and neurons were supplemented with purified CSPGs or conditioned media to assess potential mechanisms of action.

Results

The strongest evidence for genetic association was seen for SNPs mapping to the region containing the glycosyltransferase exostosin-like 2 (EXTL2), an enzyme that normally suppresses CSPG biosynthesis. Six of these SNPs showed genome-wide significant evidence for association in one of the studies with concordant and nominally significant effects in the second study. We then went on to show that a demyelinating injury to the spinal cord of EXTL2−/−mice resulted in excessive deposition of CSPGs in the lesion area. EXTL2−/−mice had exacerbated axonal damage and myelin disruption relative to wild-type mice, and increased representation of microglia/macrophages within lesions. In tissue culture, activated bone marrow-derived macrophages from EXTL2−/−mice overproduce tumor necrosis factor α (TNFα) and matrix metalloproteinases (MMPs).

Conclusions

These results emphasize CSPGs as a prominent modulator of neuroinflammation and they highlight CSPGs accumulating in lesions in promoting axonal injury.
Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions
Authors: Chen Wei , Lee Zhenghong , Awadallah Amad , Zhou Lan , Xin Wei
Published: July 2020

Background

The differential diagnosis between primary cholangiocarcinoma and metastatic pancreatobiliary adenocarcinoma is histologically challenging due to lack of distinct morphological features and reliable molecular markers. Prostate-specific membrane antigen (PSMA) is expressed in prostate epithelium and upregulated on the surface of prostatic adenocarcinoma cells. Studies have shown PSMA enzymatic activity is involved in malignancy-driven neoangiogenesis in the endothelium of tumor-associated neovasculature in breast, lung, thyroid, hepatocellular carcinoma (HCC) and urothelial cancer. Recently, PSMA-targeted imaging technology (PSMA PET-CT) detected the presence of PSMA in primary cholangiocarcinoma. However histological correlation with PSMA expression other mass lesions in the liver has not yet been studied.

Methods

72 cases of liver mass resection were collected at a tertiary hospital from 2011 to 2019. Immunohistochemical stains for PSMA and CD34 were performed. The expression of PSMA in tumor cells and associated neovascular endothelium were analyzed separately and the locations of vascular structures were confirmed by CD34 expression.

Results

Among 72 cases, 28 cases (22/72, 38.9%) showed PSMA peritumoral/vascular expression only, 3 cases (3/72, 4.2%) showed tumor cell expression only, and 2 cases (2/72, 2.8%) showed both tumor cell and peritumoral/vascular expression. The remainder (39/72, 54.2%) showed no expression. Particularly, most of primary cholangiocarcinoma showed PSMA vascular expression (13/15, 86.7%), while none of the 18 cases of metastatic pancreatobiliary adenocarcinoma were positive for PSMA (0/18, 0%) (p < 0.01). Outside of pancreatobiliary adenocarcinoma, none of the metastatic tumors, including colon and lung cancers, expressed PSMA. In 8 cases of metastatic prostate carcinoma, 3 showed PSMA expressions in tumor cells only (3/8, 37.5%) and 2 expressed PMSA in both tumor cells and neovasculature (2/8, 25.0%). Out of 22 HCC cases, 15 (15/22, 68.2%) were positive for PSMA in tumor vasculature. None of the 5 hepatic adenoma expressed PSMA (0/5, 0%).

Conclusion

Significantly enhanced tumor-associated neovascular PSMA expression was identified in primary cholangiocarcinoma, compared to metastatic pancreatobiliary adenocarcinoma. Our findings potentially provide a sensitive marker in differential diagnosis between otherwise morphologically indistinguishable cases.
46, XY disorder of sex development (DSD) complicated by a serous borderline tumor of the ovary: a case report and review of the literature
Authors: Zhao Jiangying , Peng Jiao , He Sisi , Yang Jia , Pang Xiaojun
Published: July 2020

Background

Patients with 46, XY disorder of sex development (DSD) are predisposed to the development of gonadal tumors, particularly germ cell tumors and gonadoblastoma. However, to the best of our knowledge, there are no publications in the existing literature that refer to the coexistence of 46, XY DSD and serous tumors in the ovary.

Case presentation

Here, we report the case of a 23-year-old female (social gender) patient with 46, XY DSD presenting with primary amenorrhea. Imageology revealed a huge mass in the left adnexa. Subsequent pathological analysis revealed a serous borderline tumor of the ovary.

Conclusion

Gonadal tumors of patients with 46, XY DSD are not necessarily malignant tumors and can coexist with borderline tumors with primitive corded gonads. The coexistence of DSD and serous borderline tumors is rare. Clearly, an early and accurate diagnosis plays an important role in the treatment of these patients. Although there may not be a clear correlation between the two lesions, it is vital that we specifically analyze the mechanisms involved so that we can determine whether patients with DSD are associated with an increase of developing serous borderline tumors of the gonad.
“With tramadol, I ride like a Jaguar”: a qualitative study of motivations for non-medical purpose tramadol use among commercial vehicle operators in Kumasi, Ghana
Authors: Peprah Prince , Agyemang-Duah Williams , Appiah-Brempong Emmanuel , Akwasi Adjei Gyimah , Morgan Anthony Kwame
Published: July 2020

Background

The misuse of tramadol has become a major aspect of the wider substance use challenge in recent years and is evolving into a health crisis at an alarming rate. However, literature on motivations for non-medical purpose tramadol use among commercial vehicle operators remains inadequate. The aim of this study was to document the motivations for non-medical purposes tramadol use in Kumasi. Such an understanding could inform policy direction to regulate non-medical purposes tramadol use in Ghana.

Methods

We conducted this exploratory qualitative study with 23 purposively selected commercial vehicle drivers (15) and assistants (8) in Kumasi, Ghana. Data for the study were collected through in-depth face-to-face interviews between June 2018 and March 2019. Using a thematic analytical approach, the interviews were coded and analysed.

Results

Multiple motivations for non-medical purposes tramadol use were found including those related to: (1) sexual; (2) psychological; (3) physical; and (4) economic factors. Participants also reported three main inter-linking categories of perceived tramadol adverse effects: (1) physical; (2) psychological; and (3) social effects. Although participants indicated no plans for stopping their non-medical use of tramadol any time soon, strong willingness was voiced for supporting officials in finding and dealing with non-medical purpose tramadol sellers.

Conclusion

Non-medical purposes tramadol use was associated with a confluence of factors, ranging from enhanced sexual performance to economic reasons. Based on the findings of the study and the dependence and addictive potentials of tramadol, there is the need for psychoeducational programmes for persons who misuse tramadol and enhancement of operational capacities of regulatory agencies.
COVID-19 strategy in organizing and planning orthopedic surgery in a major orthopedic referral center in an area of Italy severely affected by the pandemic: experience of the Department of Orthopedics, University of Padova
Authors: Ruggieri P. , Trovarelli G. , Angelini A. , Pala E. , Berizzi A. , Donato D.
Published: July 2020

Background

According to the required reorganization of all hospital activities, the recent COVID-19 pandemic had dramatic consequences on the orthopedic world. We think that informing the orthopedic community about the strategy that we adopted both in our hospital and in our Department of Orthopedics could be useful, particularly for those who are facing the pandemic later than Italy.

Methods

Changes were done in our hospital by medical direction to reallocate resources to COVID-19 patients. In the Orthopedic Department, a decrease in the number of beds and surgical activity was stabilized. Since March 13, it has been avoided to perform elective surgery, and since March 16, non-urgent outpatient consultations were abolished. This activity reduction was associated with careful evaluation of staff and patients: extensive periodical swab testing of all healthcare staff and swab testing of all surgical patients were applied.

Results

These restrictions determined an overall reduction of all our surgical activities of 30% compared to 2019. We also had a reduction in outpatient clinic activities and admissions to the orthopedic emergency unit. Extensive swab testing has proven successful: of more than 160 people tested in our building, only three COVID-19 positives were found, and of over more than 200 surgical procedures, only two positive patients were found.

Conclusions

Extensive swab test of all people (even if asymptomatic) and proactive tracing and quarantining of potential COVID-19 positive patients may diminish the virus spread.
Influence of marital status on overall survival in adult patients with chordoma: a SEER-based study
Authors: Tang Chao , Wang Ruiliang , Lu Qingguo , Wang Shantao , Jia Gen , Cao Pengfei , Nie Xinfa , Zhang Hailong
Published: July 2020

Background

As a rare primary bone tumor, no studies have reported the relationship between prognosis and marital status in patients with chordoma.

Methods

We classified patients with chordoma identified from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016 into four groups: married, divorced/separated, widowed, and single groups. Kaplan-Meier curves with log-rank test and Cox regression were used to analyze the effect of marital status on overall survival (OS).

Results

A total of 1080 patients were included in the study: 700 (64.8%) were married, 88 (8.1%) were divorced/separated, 78 (7.2%) were widowed, and 214 (19.8%) were single. Among the 4 groups, the 5-year OS (45.2%), 10-year OS (12.5%), and median OS (56.0 months) were the lowest in the widowed group. After including age, sex, primary site, marital status, disease stage, tumor size, histological type, and treatment pattern, multivariate analysis showed that marital status was still an independent risk factor for patients with chordoma, and widowed patients had the lowest OS (hazard ratio [HR] 1.71; 95% confidence interval [CI] 1.25–2.33, p < 0.001) compared with married patients. Similar results were observed after stratifying the primary site and disease stage.

Conclusion

Marital status was an independent prognostic indicator for adult patients with chordoma, and marital status was conducive to patient survival. Compared with married patients, widowed patients have a higher risk of death.
Enterogenic empyema complicating colobronchial fistula: a case report
Authors: Yang Yong , He Jinghu , Wang Wei , Li Ang , Jiang Gening , Wang Hantao , Duan Liang
Published: July 2020

Background

Enterogenic empyema is an uncommon complication of colobronchial fistula (CBF). We reported a case of enterogenic empyema patient after surgery for CBF.

Case presentation

A 66-year-old gentleman presented with persistent fever and repeated hemoptysis for 8 months. Computed tomography of the thorax confirmed the presence of a consolidation mass located in the right middle lobe and an air space near the right rib angle. During exploration, CBF was found. The patient underwent right middle and lower lobectomy together with closure of colonic and diaphragmatic perforation. The colon closure and diaphragm closure ruptured after surgery, leading to enterogenic empyema. Adequate drainage, sustained high protein diet, and antibiotic treatment eventually resulted in full recovery.

Conclusion

This is the first report of enterogenic empyema complicating CBF.
Outcomes of surgical resection for pulmonary metastasis from ovarian cancer
Authors: Kanzaki Ryu , Okami Jiro , Takami Koji , Iwasaki Teruo , Ikeda Naoki , Funakoshi Yasunobu , Sakamaki Yasushi , Kodama Ken , Yokouchi Hideoki , Kadota Yoshihisa , Ose Naoko , Shintani Yasushi ,   for Thoracic Surgery Study Group of Osaka University (TSSGO)
Published: July 2020

Background

Due to its rarity, information on pulmonary metastasectomy for pulmonary metastasis from ovarian cancer is limited.

Methods

Cases of pulmonary metastasectomy for ovarian cancer were collected in a multi-institutional setting and the outcomes were analyzed.

Results

Among 1508 cases in which pulmonary resection was performed to treat pulmonary metastasis from tumors of various organs, 6 cases (0.4%) involved pulmonary metastasis from ovarian cancer. The mean age was 61 years (range, 39–75 years). The histological types were undifferentiated carcinoma in 2 patients, and clear cell adenocarcinoma, serous papillary cystadenocarcinoma, serous adenocarcinoma, and endometroid adenocarcinoma in 1 patient each. One patient (17%) had a history of liver metastasis at the time of pulmonary resection. The median disease-free interval was 22 months (range, 0 [synchronous]-188 months). The tumor was solitary in 5 patients (83%). The mean tumor size was 15 mm (range, 5–23 mm). All 6 patients underwent complete resection. The type of resection was wide wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 1 patient. Four patients (67%) received postoperative chemotherapy. Thus far, 4 patients (67%) have experienced recurrence after pulmonary resection. In terms of outcomes, 1 patient who had synchronous pulmonary metastasis with the primary tumor died in the early period after pulmonary resection, 1 patient is alive without recurrence after a short follow-up period (5 months), 3 patients have achieved mid- to long-term survival and are alive with disease (38–61 months), and 1 patient achieved long-term (61 months) disease-free survival.

Conclusions

Patients with pulmonary metastasis from ovarian cancer who fulfill the eligibility criteria for pulmonary metastasectomy are rare. Pulmonary metastasectomy for ovarian cancer can provide favorable outcomes in highly selected patients. Patients with synchronous pulmonary metastasis from ovarian cancer are not good candidates for pulmonary metastasectomy.
A case report of thrombotic complete obstruction of the ascending aorta as a complication of Venoarterial extracorporeal membrane oxygenation support: steps to prevent thrombosis
Authors: Nishihara Tasuku , Kudamatsu Natsuko , Hamada Taisuke , Nakata Yukihiro , Yamamoto Waichi , Nandate Hideyuki , Namiguchi Kenji , Nishimura Takashi , Izutani Hironori , Yorozuya Toshihiro
Published: July 2020

Background

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential device in the field of emergency and intensive-care medicine. However, long-term use of VA-ECMO has various severe complications, including thrombosis.

Case presentation

A 60-year-old man underwent his third aortic root replacement using a homograft because of infectious endocarditis. Although the operation was difficult because of severe adhesion caused by the two previous interventions, aortic root replacement using a homograft was performed. At the time of withdrawal from cardiopulmonary bypass, the maintenance of hemodynamics was difficult because of bleeding from the surgical site, leading to hypovolemic shock. Cardiac function subsequently deteriorated; therefore, VA-ECMO was established and the operation was finished. Three days later, thrombus was formed inside the homograft and completely occluded ascending aorta. Evacuation of hematoma was performed, however, cardiac function was not ameliorated. Eventually, the patient had brain infarction and died. To prevent thrombus formation in very severe low cardiac output cases under VA-ECMO management after surgery, to prevent the stagnation of the blood flow from VA-ECMO will be necessary because anticoagulant therapy will be difficult. Impella ventricular assist device which is recently used widely generates anterograde blood flow and effectively prevents stagnation.

Conclusions

To prevent thrombus formation in cases of very severe low cardiac output, Impella® should be combinatorially introduced from the beginning of VA-ECMO establishment to prevent thrombosis.
Navigating the crisis landscape: engaging the ministry of health and United Nations agencies to make abortion care available to Rohingya refugees
Authors: Fetters Tamara , Rubayet Sayed , Sultana Sharmin , Nahar Shamila , Tofigh Shadie , Jones Lea , Samandari Ghazaleh , Powell Bill
Published: July 2020

Background

Unintended and unwanted pregnancies likely increase during displacement, making the need for sexual and reproductive health (SRH) services, especially safe abortion, even greater. Attention is growing around barriers to safe abortion care for displaced women as donor, non-governmental and civil society actors become more convinced of this need and reports of systematic sexual violence against women are more widely documented around the world. Yet a reluctance to truly change practice remains tied to some commonly reported reasons: 1) There is no need; 2) Abortion is illegal in the setting; 3) Donors do not fund abortion services, and; 4) Abortion is too complicated during acute emergencies. While there is global progress towards acknowledging the deficit of attention and evidence on abortion services in humanitarian settings, improvements in actual services have yet to follow.

Case presentation

In August 2017, over 700,000 Rohingya refugees fled Myanmar for Bangladesh. Women and girls fled homes and communities - many experienced terrible violence - and arrived at camps in Bangladesh with SRH needs, including unwanted pregnancies. With funding from UNFPA and others, Ipas trained providers and established safe induced abortion (called menstrual regulation (MR) in Bangladesh) and contraception services in October 2017.

Ipas Bangladesh initiated the trainings in coordination with the government’s health system and international aid agencies. Training approaches were modified so that providers could be trained quickly with minimal disruption to their ability to provide care. Within one month of the arrival of refugees, MR services had been established in eight facilities, for the first time during an acute emergency. By mid-2019, over 300 health workers from 37 health facilities had attended training in MR, postabortion care (PAC), and contraception. Over 8000 Rohingya refugees have received abortion-related care, more than three-quarters of which were MR procedures; over 26,000 women and girls have received contraception at these facilities.

Conclusions

This study demonstrates demand for abortion care exists among refugees. It also illustrates that these needs could have been easily overlooked in the complex environment of competing priorities during an emergency. When safe abortion services were made available, with relative ease and institutional support, women sought assistance, saving them from complications of unsafe abortions.
Roles of hsa-miR-12462 and SLC9A1 in acute myeloid leukemia
Authors: Jia Yan , Liu Wei , Zhan Hui-En , Yi Xiao-Ping , Liang Hui , Zheng Qi-Li , Jiang Xin-Ya , Zhou Hai-Yan , Zhao Liang , Zhao Xie-Lan , Zeng Hui
Published: July 2020

MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for acute myeloid leukemia (AML) diagnosis and prognosis. In this study, we defined a novel miRNA, hsa-miR-12462, through small RNA sequencing of the bone marrow (BM) cells from 128 AML patients. Overexpression of hsa-miR-12462 in AML cells (U937 and HL-60) significantly decreased their growth rate when compared with those of the wild-type and MOCK controls. In a xenograft mouse model, tumor weight and size in the mice bearing the U937 cells with hsa-miR-12462 overexpression were significantly reduced when compared with those bearing the mock cells. The AML cells overexpressing hsa-miR-12462 had increased sensitivity to cytarabine chemotherapy. Combining the data from the MiRDB, an online microRNA database (http://mirdb.org), with the RNA-sequencing results, SLC9A1 was predicted to be one of the targets of hsa-miR-12462. hsa-miR-12462 was further confirmed to bind exclusively to the 3′UTR of SLC9A1 in U937 cells, leading to downregulation of SLC9A1. In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to cytarabine chemotherapy via downregulation of SLC9A1.
Crosstalks between inflammasome and autophagy in cancer
Authors: Chung Chaeuk , Seo Wonhyoung , Silwal Prashanta , Jo Eun-Kyeong
Published: July 2020

Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often associated with the pathogenesis of numerous cancers. In addition, they can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses, including cancer. Multiple molecular mechanisms connect the autophagy pathway to inflammasome activation and, through this, may influence the outcome of pro-tumor or anti-tumor responses depending on the cancer types, microenvironment, and the disease stage. In this review, we highlight the rapidly growing literature on the various mechanisms by which autophagy interacts with the inflammasome pathway, to encourage additional applications in the context of tumors. In addition, we provide insight into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis. We also explore the challenges and opportunities of using multiple small molecules/agents to target the autophagy/inflammasome axis and their effects upon cancer treatment. Finally, we discuss the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophagy or inflammasome as anti-cancer strategies, although it remains underexplored in terms of their crosstalks.
A narrative review of estimands in drug development and regulatory evaluation: old wine in new barrels?
Authors: Mitroiu M. , Oude Rengerink K. , Teerenstra S. , Pétavy F. , Roes K. C. B.
Published: July 2020

Background

An estimand defines the target of estimation for a clinical trial through specification of the treatment, target population, variable, population-level summary and of the strategies for intercurrent events. A carefully defined estimand aligns the clinical trial design and analysis with the scientific question of interest and adequately accounts for so-called intercurrent events. The ICH E9(R1) addendum suggests five estimand strategies. We evaluated to what extent current practice in drug development and regulatory assessment fits in the estimand framework.

Methods

We systematically evaluated what estimands, especially what strategies for intercurrent events are advised in European Medicines Agency disease guidelines, used in sponsors’ trials and additionally requested by the European Medicines Agency in assessment dossiers. We selected four therapeutic areas: nervous system, oncology, cardiovascular diseases and respiratory diseases. For each, we evaluated all disease guidelines with approved drugs, the dossiers of the most recently approved drugs matching the guidelines and corresponding regulatory questions.

Results

Strategies for intercurrent events were present in 18 (53%) of 34 guidelines, in all 34 sponsor documentations and in 15 (44%) of 34 sets of regulatory questions. Treatment policy was advised in 13 (38%) guidelines and was applied in 9 corresponding sponsor documentations. Of these 9, it was the sole strategy in 4 cases and accompanied by another strategy in 5 cases. Hypothetical strategy was not advised in guidelines. However, it was the leading strategy applied in 25 (74%) sponsor documentations. Composite strategy was advised in 3 (9%) guidelines and applied accompanied by another strategy in 2 corresponding sponsor documentations. While on treatment strategy was not advised in guidelines, but was applied in 2 sponsor documentations. Principal stratum strategy was advised in 2 guidelines but not applied in corresponding sponsor documentations. Of the regulatory questions, treatment policy was present in 2 cases (6%), hypothetical in 6 cases (18%), composite in 6 cases (18%) and while on treatment in 1 case (3%).

Conclusions

Estimand attributes are present in guidelines, sponsor documentations and regulatory questions, but not described as estimands. Treatment policy was most often advised in guidelines, but hypothetical was the leading strategy applied in sponsor documentations. Thus, results indicate not a full concordance between the regulatory target of estimation and what is actually estimated. The lack of concordance was mostly due to limitations in collection of intercurrent events data to enable a treatment policy strategy. There is, therefore, a need to better define estimands at the design stage and throughout the applications dossiers and assessment reports.
Efficacy of brief dynamic interpersonal therapy in patients with major depressive disorder: a prospective, multicenter randomized controlled trial protocol
Authors: Wang Lanlan , Wang Qian , Jiang Wenhui , Luo Jianfeng , Tong Jun , Li Xiaosi , Fang Fang , Wang Hongyan , Zhao Wenqing , Koszycki Diana , Qiu Jianyin
Published: July 2020

Background

In China, psychodynamic psychotherapies are widely used as a treatment for depression. However, very few efficacy studies of psychodynamic therapies have been conducted with the Chinese population. This paper describes a study protocol of a multicenter randomized controlled trial of dynamic interpersonal psychotherapy (DIT), a brief manualized depression-focused intervention, in Chinese adults with major depressive disorder (MDD).

Methods

Recruitment is planned in five hospitals. Two hundred forty patients with MDD will be randomly allocated on a 1:1:1 basis to either medication plus DIT, medication plus an active control psychotherapy, or medication alone. Patients will be assessed at baseline and at weeks 2, 4, 8, 12, and 16 during the acute treatment phase and 1, 3, 6, and 12 months posttreatment. The primary outcome is change from baseline in the 17-item Hamilton Depression Rating Scale, administered by independent raters who are blind to treatment allocation. The Hamilton Anxiety Rating Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, response, remission and relapse rates, self-assessment of overall efficacy and satisfaction of patients, and side effect profiles are secondary measures.

Discussion

This will be the first multicentered RCT in China to assess the efficacy of a brief psychodynamic intervention for MDD. The study has the potential to inform clinical treatment guidelines for the treatment of depression in China.

Trial registration

ChiCTR, ChiCTR1800016970. Registered on July 5, 2018
Communities for Healthy Living (CHL) A Community-based Intervention to Prevent Obesity in Low-Income Preschool Children: Process Evaluation Protocol
Authors: Beckerman-Hsu Jacob P. , Aftosmes-Tobio Alyssa , Gavarkovs Adam , Kitos Nicole , Figueroa Roger , Kalyoncu Z. Begum , Lansburg Kindra , Yu Xinting , Kazik Crystal , Vigilante Adrienne , Leonard Jessie , Torrico Merieka , Jurkowski Janine M. , Davison Kirsten K.
Published: July 2020

Background

Process evaluation can illuminate barriers and facilitators to intervention implementation as well as the drivers of intervention outcomes. However, few obesity intervention studies have documented process evaluation methods and results. Community-based participatory research (CBPR) requires that process evaluation methods be developed to (a) prioritize community members’ power to adapt the program to local needs over strict adherence to intervention protocols, (b) share process evaluation data with implementers to maximize benefit to participants, and (c) ensure partner organizations are not overburdened. Co-designed with low-income parents using CBPR, Communities for Healthy Living (CHL) is a family-centered intervention implemented within Head Start to prevent childhood obesity and promote family well-being. We are currently undertaking a randomized controlled trial to test the effectiveness of CHL in 23 Head Start centers in the greater Boston area. In this protocol paper, we outline an embedded process evaluation designed to monitor intervention adherence and adaptation, support ongoing quality improvement, and examine contextual factors that may moderate intervention implementation and/or effectiveness.

Methods

This mixed methods process evaluation was developed using the Pérez et al. framework for evaluating adaptive interventions and is reported following guidelines outlined by Grant et al. Trained research assistants will conduct structured observations of intervention sessions. Intervention facilitators and recipients, along with Head Start staff, will complete surveys and semi-structured interviews. De-identified data for all eligible children and families will be extracted from Head Start administrative records. Qualitative data will be analyzed thematically. Quantitative and qualitative data will be integrated using triangulation methods to assess intervention adherence, monitor adaptations, and identify moderators of intervention implementation and effectiveness.

Discussion

A diverse set of quantitative and qualitative data sources are employed to fully characterize CHL implementation. Simultaneously, CHL’s process evaluation will provide a case study on strategies to address the challenges of process evaluation for CBPR interventions. Results from this process evaluation will help to explain variation in intervention implementation and outcomes across Head Start programs, support CHL sustainability and future scale-up, and provide guidance for future complex interventions developed using CBPR.

Trial registration

ClinicalTrials.gov, NCT03334669. Registered on October 10, 2017
Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: statistical analysis plan for a randomised controlled trial (UPGRADE trial)
Authors: Haal Sylke , Guman Maimoena S. S. , de Brauw L. Maurits , van Veen Ruben N. , Schouten Ruben , Fockens Paul , Gerdes Victor E. A. , Dijkgraaf Marcel G. W. , Voermans Rogier P.
Published: July 2020

Background

Approximately 8–15% of patients undergoing bariatric surgery develop symptomatic gallstone disease within 24 months after surgery. Ursodeoxycholic acid (UDCA) seems to effectively prevent the formation of gallstones detectable by ultrasound after bariatric surgery. The aim of the UPGRADE trial is to provide evidence on the prophylactic use of UDCA in preventing symptomatic gallstone disease postoperatively.

Methods

The UPGRADE trial is designed as a randomised, placebo-controlled, double-blind multicentre trial in patients with morbid obesity undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Patients are randomly assigned to either UDCA 900 mg daily for 6 months or placebo treatment. This paper details the statistical analysis plan (SAP) of this trial and was submitted before outcome data were available.

Results

The primary endpoint of this trial is symptomatic gallstone disease within 24 months after bariatric surgery, defined as admission or hospital visit for symptomatic gallstone disease. Secondary outcomes consist of the development of gallstones/sludge on ultrasound at 24 months in the gallstone-negative group at baseline, presence of gallstones/sludge on ultrasound at 24 months, number of cholecystectomies, side effects of UDCA, therapy compliance, quality of life, costs and revenues. Analyses will be completed according to this pre-specified SAP. The main analysis will be performed as a standard ITT analysis using the chi-squared test.

Discussion

The UPGRADE trial will show if prophylactic use of UDCA reduces the incidence of symptomatic gallstone disease after bariatric surgery. Unforeseen deviations from the SAP at the time of analysis will be motivated and discussed.

Trial registration

The Netherlands Trial Register NL5954. Registered on 21 November 2016.
Quantification of circulating microRNAs by droplet digital PCR for cancer detection
Authors: Cirillo Priscila D. R. , Margiotti Katia , Mesoraca Alvaro , Giorlandino Claudio
Published: July 2020

Objective

Circulating cell-free microRNAs (miRNAs) which consist of short-sequence RNAs are released from cells into the blood stream and has emerged as new biomarkers in the clinical cancer diagnosis and treatment. For instance, ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, development of a diagnostic tool that enables the ovarian cancer diagnosis in earlier stages is urgent.

Results

We have described an efficient protocol for an accurate absolute quantification of circulating miRNAs in healthy and ovarian cancer serum samples. Our data showed that ddPCR methodology can accurately measure circulating miRNAs levels and that can be a useful tool in biomarkers discovery for ovarian cancer detection.
Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease
Authors: Liu Qian , Jiao Yihang , Yang Weijian , Gao Beiyao , Hsu Daniel K. , Nolta Jan , Russell Michael , Lyeth Bruce , Zanto Theodore P. , Zhao Min
Published: July 2020

Background

Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer’s disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electrode. To circumvent this problem, we assessed whether intracranial electrical stimulation to the brain affects neurogenesis in a mouse model of Alzheimer’s disease (5xFAD).

Methods and results

We used Ki67, Nestin, and doublecortin (DCX) as markers and determined that neurogenesis in both the subventricular zone (SVZ) and hippocampus were significantly reduced in the brains of 4-month-old 5xFAD mice. Guided by a finite element method (FEM) computer simulation to approximately estimate current and electric field in the mouse brain, electrodes were positioned on the skull that were likely to deliver stimulation to the SVZ and hippocampus. After a 4-week program of 40-Hz intracranial alternating current stimulation (iACS), neurogenesis indicated by expression of Ki67, Nestin, and DCX in both the SVZ and hippocampus were significantly increased compared to 5xFAD mice who received sham stimulation. The magnitude of neurogenesis was close to the wild-type (WT) age-matched unmanipulated controls.

Conclusion

Our results suggest that iACS is a promising, less invasive technique capable of effectively stimulating the SVZ and hippocampus regions in the mouse brain. Importantly, iACS can significantly boost neurogenesis in the brain and offers a potential treatment for AD.
Patient with rheumatoid arthritis with deep vein thrombosis presenting as a calf strain: a case report
Authors: Lewis Trevor
Published: July 2020

Background

Patients with rheumatoid arthritis experience various comorbidities, including cardiovascular disease. More data and awareness exist regarding the adverse effects of rheumatoid arthritis affecting the arterial side of the cardiovascular system, such as stroke or myocardial infarction, than regarding adverse venous complications, such as deep vein thrombosis and pulmonary embolism. Rheumatoid arthritis affects more women than men, and the risk of venous thromboembolism in rheumatoid arthritis tends to increase with age; therefore, the presentation in this case report of deep vein thrombosis in a nonsmoking, young, fit man with rheumatoid arthritis is rare. This patient was sent away from a minor injuries unit with a diagnosis of a calf strain. Further assessment at an accident and emergency department later in the day confirmed deep vein thrombosis via ultrasonography. This case report underlines the need for vigilance because deep vein thrombosis is a risk factor in rheumatoid arthritis, even in young, male, and physically fit individuals.

Case presentation

A nonsmoking 39-year-old Caucasian man with a 2-year history of rheumatoid arthritis presented for assessment at a private physiotherapy clinic with a 4-week history of right-sided posterior calf pain that had developed following exercise at a gym. The patient therefore believed his symptoms were due to a calf strain. Findings at physiotherapy assessment suggested that the actual cause of the patient’s symptoms were as a result of deep vein thrombosis. The patient was directed to a local minor injuries unit with a referral letter from the author outlining this diagnosis. Following clinical assessment at the minor injuries unit, the patient was told that there was no likelihood of deep vein thrombosis, and his diagnosis was a calf strain. The patient harbored concerns at this point and decided to seek further medical opinion at a nearby accident and emergency department, where deep vein thrombosis was diagnosed using ultrasonography, and the patient was commenced on anticoagulants.

Conclusions

Venous thromboembolism risk in rheumatoid arthritis is stated as being less recognized as an arterial complication. This is borne out by this patient’s clinical journey, wherein his youth, fitness, athletic appearance, and onset of symptoms during exercise were said to suggest a diagnosis of a calf strain at a minor injuries unit. Ultrasonography at a different accident and emergency unit later that day ultimately was used to diagnose deep vein thrombosis.
Exosomal lncRNAs from mesenchymal stem cells as the novel modulators to cardiovascular disease
Authors: Huang Ying
Published: July 2020

Aim

Mesenchymal stem cells (MSCs) have been identified as potential therapeutic candidates for cardiovascular disease (CVD). However, the molecular mechanism underlying their therapeutic effects is unknown.

Findings

Recently, Chen et al. showed that an exosomal lncRNA derived from MSCs protected against cardiomyocyte apoptosis in vivo, which provided new insight into our understanding of the functions of MSCs. Other exosomal lncRNAs from MSCs have been shown to play pivotal roles in the development of CVD.

Conclusion

Exosomal lncRNAs are important molecules in the application of MSCs, which reveals, at least in part, the functional mechanism of MSCs.