bluuebunny/crossref_metadata_2025 huggingface dataset:
TRAMADOL-ASSOCIATED BILATERAL CYSTOID MACULAR EDEMA
Authors: Miere Alexandra , Bustros Youssef , Pallone Carlotta , Barbalan Elena A. , Amoroso Francesca , Zambrowski Olivia , Souied Eric H.
Published: November 2020

Purpose:

To describe a case of bilateral cystoid macular edema in a patient with long-standing tramadol hydrochloride use.

Methods:

Observational case report.

Results:

A 73-year-old female patient was referred for progressive, bilateral decreased visual acuity. The patient was phakic with a best-corrected visual acuity at presentation was 20/50 on the right eye and 20/64 on the left eye. The patient had a history of low back pain and had been on tramadol hydrochloride 200 mg/day for 16 years. Bilateral cystoid macular edema was confirmed by means of multimodal imaging, including optical coherence tomography angiography. Tramadol intake was progressively reduced over one month and then completely interrupted. At 3 months follow-up, the cystoid macular edema had completely resolved and the best-corrected visual acuity improved in both eyes.

Conclusion:

Cystoid macular edema may be associated with longstanding treatment with tramadol hydrochloride. Tramadol hydrochloride–associated cystoid macular edema is described and its resolution on tramadol cessation.
Understanding How Providers and Staff Make Decisions About Where to Refer Their Patients
Authors: Makovkina Evguenia , Kern Lisa M.
Published: November 2020

Value-based payment incentivizes primary care providers (PCPs) to refer patients to specialists inside their own organization. “Outmigration” of patients to specialists in other organizations is common, yet why it occurs is not clear. We conducted qualitative interviews of PCPs, nurses, and administrative staff at primary care practices in a physician organization (PO) to determine reasons for outmigration. While participants reported that they preferred making within-PO referrals, they identified 18 barriers to within-PO referrals, which often led to patients receiving care elsewhere. Many of these barriers are potentially modifiable and could inform the design of future interventions to decrease unnecessary outmigration.
Clinical characteristics and treatment effects of astragalus injection in non-pediatric patients with acute fulminant myocarditis
Authors: Yang Hongmin , Lu Yang , Yang Han , Yuan Jing
Published: November 2020

To explore the clinical characteristics of non-pediatric patients with acute fulminant myocarditis (AFM) and evaluate the treatment effects of astragalus injection on this disease.

A total of 54 AFM patients were screened out from 586 patients with acute myocarditis, admitted to the department of cardiology between January 2011 to June 2018. The demographic and clinical data, investigations, treatments, and short-term outcomes were collected and retrospectively analyzed.

The mean age of the 54 AFM patients was 34 ± 16.5 years old (range: 13–70 years), including 24 (44.5%) men and 30 (55.5%) women, with a high incidence in 2 age groups: 13–19 and 40–49 years old, despite an inverse trend to the increase of age. All these cases were admitted in emergency conditions: 26 (48.1%) cardiogenic shock, 18 (33.4%) malignant arrhythmias, 8 (14.8%) severe heart failure, and 2 (3.7%) acute pericardial tamponade. Apart from first-aid measures, 37 (68.5%) patients received astragalus injection. During hospitalization, 11 (20.4%) patients died, and 4 (36.3%) of them were from astragalus group while 7 (63.7%) of them from without-astragalus group (P=0.03). Furthermore, the levels of cardiac injury biomarkers, renal function and left ventricular ejection fraction of astragalus group were significantly improved compared with those of without-astragalus group at discharge (all P < .05).

Middle-aged people were also prone to AFM. And cardiac shock was the most common, while acute pericardial tamponade was a rare presentation in non-pediatric AFM patients. Astragalus was a potential adjuvant medicine for the treatment of AFM.
Therapeutic efficacy and safety of Kangfuxin in combination with rabeprazole in the treatment of peptic ulcer
Authors: Lin Meisi , Zhang Siyuan , Zhang Minyue , Shi Jinfeng , Zhang Chen , Luo Ruifeng , You Jieshu , Sun Jiayi , Zhang Jinming , Gao Fei
Published: November 2020

Background:

Kangfuxin (KFX), a well-known Chinese patent medicine which extracted from Periplaneta americana, is widely used as an adjuvant in the treatment of peptic ulcers (PUs) with proton pump inhibitors (PPIs) such as rabeprazole, in China. However, no clear consensus has been reached on the efficacy for PU treatment.

Methods:

We searched in 7 electronic databases to find randomized controlled trials (RCTs) completed before May 31, 2020 to explore the clinical efficiency of KFX plus rabeprazole in the treatment of PU. Risk ratio (RR) corresponding to 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by both Egger's and Begg's tests. Statistical analyses were performed using RevMan 5.4 and Stata version 10.0.

Results:

Twenty-five RCTs, comprising 2555 PU patients, were included in this study. Meta-analysis showed that, when compared with rabeprazole-based treatment alone, KFX plus rabeprazole significantly improved the healing rate (RR = 1.34, 95% CI 1.25–1.44) and overall response rate of ulcers (RR = 1.16, 95% CI 1.13–1.20), alleviated the clinical symptoms of PU (RR = 1.14, 95% CI 1.08–1.21), and reduced the recurrence of PU (RR = 0.38, 95% CI 0.24–0.61) without an increase in the occurrence of adverse events (RR = 0.92, 95% CI 0.66–1.28).

Conclusion:

Our study suggests that KFX combined with rabeprazole showed positive therapeutic effects and is safe for treating PU, which may provide more reliable evidence for the clinical use of KFX in the treatment of PU.
Effectiveness and safety of massage in the treatment of restless legs syndrome
Authors: Hu Shasha , He Xingwei , Zhang Yajing , Hu Songfeng , He Fan , Zhao Fenfen , Zhang Qin , Liu Tingping , Wang Changkang
Published: November 2020

Background:

Restless legs syndrome (RLS), known as a kind of neurological disease, is prevalent but easy to be ignored. Studies have demonstrated that massage therapy can effectively reduce the symptoms of patients with RLS and improve their quality of life. However, the efficacy of massage therapy for RLS is still controversial. Therefore, this protocol aims to evaluate the reliability of massage therapy in treating RLS in a thorough way.

Methods:

We will search relevant randomized controlled trials from Chinese Biomedical Literature Database, Chongqing VIP, CNKI, Wanfang, Web of Science, Cochrane Library, PubMed, and EMBASE, when publication status and language are not considered and the time limit ends with September 6, 2020. Two experienced researchers will use RevMan V.5.3 software to perform the selection of literature, data collection, data analysis and synthesis separately. Besides, the quality of trials involved in this study will be measured with the Cochrane bias risk assessment tool.

Results:

This protocol will be applied to carry out a systematic evaluation of the massage therapy purposed to treat RLS for its effectiveness and safety.

Conclusion:

The review will provide a credible evidence suggesting whether massage therapy is a reliable intervention for RLS.

INPLASY registration number:

INPLASY202090038
Rivaroxaban-associated intracranial hemorrhage in Saudi atrial fibrillation patients
Authors: Alkhotani Amal , Alrishi Nouf , Alharthi Meshari , Alzahrani Waleed
Published: November 2020

Atrial fibrillation is the most common cardiac arrhythmia. Anticoagulation therapy effectively reduces systemic embolization in patients with non-valvular atrial fibrillation, but intracranial hemorrhage (ICH) is a major possible complication. This study assessed the real-time rate of rivaroxaban-associated ICH in Saudi patients.

We retrospectively reviewed patients with ICH during rivaroxaban therapy, assessing clinical features and outcomes.

Four cases out of 690 patients were identified in total, indicating an incidence of ICH during rivaroxaban therapy of 0.58%. Hematoma expansion developed in 1 case. Three out of four patients were discharged after ICH, and 1 patient died.

The incidence of rivaroxaban-related ICH was similar to that previously reported, and the risk of hematoma expansion was low. Further studies are required to validate our results.
Behavioral problems of Mandarin-speaking late-talking toddlers and preschool aged children
Authors: Lu Hsin-Hui , Tsao Feng-Ming , Tsai Jeng-Dau
Published: November 2020

This study aimed to examine whether Mandarin-speaking late-talking (LT) toddlers have a higher incidence of behavioral problems than typical language developing (TLD) children in toddlerhood and at preschool age from a community sample in Taiwan.

This prospective case–control study comprised 32 LT and 32 TLD toddlers. Participants’ parents provided reports about their children at 2 and 4 years using the Child Behaviors Checklist, a component of the Achenbach System of Empirically Based Assessment.

The results indicated that compared to the TLD group, a higher percentage of the LT group was at risk of behavioral problems at both two and four years. Similarly, the chance of internalizing problems was higher in the LT group than the TLD group at both ages.

The findings indicated that LT toddlers are at risk for behavioral problems not only in toddlerhood, but also at preschool age. Thus, it is crucial to identify LT toddlers with behavioral problems and enroll them in early developmental evaluation programs in their communities and also include them in early intervention programs if necessary. In addition, the underlying mechanism of the association between language delay and behavioral problems in children needs to be longitudinally explored from a young age.
Efficacy and safety of traditional Chinese medicine for erosive oral lichen planus
Authors: You Yanyan , Huang Xiaojin , Chen Yunhui , You Yu
Published: November 2020

Background:

Oral lichen planus (OLP) is a common disease among oral mucous membrane diseases. Erosive oral lichen planus (EOLP) is a type of OLP, it has a potential tendency of cancerization. There have been some randomized controlled trials (RCTs) using Traditional Chinese Medicine (TCM) to treat EOLP. No systematic review on the RCTs of TCM for EOLP has been reported, so we would propose a study protocol that aims to evaluate the evidence the efficacy and safety of TCM for treating patients with EOLP.

Methods:

The following databases from the inception to June 30, 2020 electronically, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, VIP, Wanfang database, China Biomedical Literature Database will be searched. RCTs that meet the pre-specified eligibility criteria will be included. RevMan software (V5.3) will be performed data synthesis following data extraction and publication risk assessment. Subgroup and sensitivity analysis will be performed according to the condition of included RCTs. The primary outcomes include visual analogy scale, laboratory immune indicators, and scores of oral lesions and signs. Additional outcomes are clinical effective rate, adverse event rate, and recurrence rate. The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of the evidence.

Results:

This study will provide a well-reported synthesis of RCTs on the efficacy and safety of TCM in the treatment of EOLP.

Conclusion:

This systematic review protocol will be helpful for providing evidence of whether TCM is an effective and safe therapeutic approach for patients with EOLP.

Ethics and dissemination:

Ethical approval is not necessary as this protocol is only for systematic review and it does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation.

Systematic review registration:

PROSPERO CRD42020172366.
The efficacy of enteral nutrition combined with accelerated rehabilitation in non-small cell lung cancer surgery
Authors: Ji Xiaona , Ding Haiyan
Published: November 2020

Objective:

To investigate the effect of enteral nutrition combined with accelerated rehabilitation in treating the non-small cell lung cancer (NSCLC).

Methods:

It is a randomized controlled experiment to be carried out from June 2021 to December 2021. It was permitted through the Ethics Committee of Cancer Hospital Affiliated to Shandong First Medical University (00923876). 100 patients are included in the study. The inclusion criteria contain: (1) patients with NSCLCs receiving surgery as the primary treatment; (2) over 18 years of age. The exclusion criteria are as follows: (1) age ≥65 years; (2) severe metabolic and systemic diseases, such as diabetes, hypertension, or severe liver and kidney dysfunction; (3) the body mass index <18.5 kg/m2; (4) patients who have received preoperational radiotherapy or chemotherapy. Patients in the control group are provided routine nutrition, including preoperative nutritional risk screening and assessment and preoperative nutrition education and dietary guidance, while patients in the nutrition group are provided additional enteral nutrition preparations combined with accelerated rehabilitation as in the control group. The primary outcomes include the perioperative change of serum albumin, serum prealbumin, hemoglobin, and total lymphocyte counts. The second outcomes include length of hospitalization, quality of life, and risk of postoperative complications.

Results:

Table 1 shows the comparison of indicators after surgery between the 2 groups.

Conclusion:

Enteral nutrition combined with accelerated rehabilitation appears to be beneficial in decreasing the complications and improving postoperative recovery after NSCLC surgery.
Clinical effect of catgut implantation at acupoints for the treatment of simple obesity
Authors: Chen Xia , Huang Wei , Wei Dan , Ding De-Guang , Jiao Yang , Pan Hong-Ling , Jin Yi-Ting , Zheng Yi-Wei , Zhang Yan-Ji , Zhang Ying-Rong , Liu Yi-Ran , Zhou Zhong-Yu
Published: November 2020

Background:

Catgut implantation at acupoints (CIA) is a subtype of acupuncture that has been widely used to treat simple obesity, but evidence for its effectiveness remains scarce. The aim of this study is to evaluate the efficacy and safety of treating simple obesity with CIA.

Objective:

This clinical trial aims to evaluate the effectiveness and safety of CIA used for treatment of simple obesity.

Methods:

This is a multicentre, randomized, parallel, sham-controlled clinical trial. A total of 216 patients with simple obesity will be recruited. They will be randomly assigned in a 1:1 ratio to either the CIA group or the sham control group. All treatments will be given once every 2 weeks. The primary outcome measure is the rate of waistline reduction. Secondary outcome measures are the rates of reduction of body measurements, including weight, body mass index (BMI), hipline, waist-hip-ratio (WHR) and body fat percentage (BFP), the changes in scores on scales, including the Impact of Weight on Quality of Life Questionnaire (IWQOL-Lite), Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HAD) and the Self-Esteem Scale (SES), Outcomes will be evaluated at baseline and at weeks 4, 8, 12, 16, 28, and 40, respectively. All adverse events that occur during this study will be recorded. If any participant withdraws from the trial, an intention-to-treat analysis (ITT) will be performed.

Conclusion:

This is a randomized, sham-controlled trial of CIA treatment for simple obesity. The results of this trial will provide more evidence on whether CIA is efficacious and safe for treating obesity.

Trial registration:

ClinicalTrials.gov Identifier: NCT02936973. Registered on October 18, 2016.
Traditional Chinese medicine for irritable bowel syndrome
Authors: Yao Cheng-Jiao , Li Yi-Lin , Pu Meng-Jun , Luo Li-Hong , Feng Pei-Min
Published: November 2020

Background:

Irritable bowel syndrom (IBS) is a common functional gastrointestinal disorder which is characterized as recurrent abdominal pain, abdominal discomfort, and abnormal bowel habits such as diarrhea, constipation, both or alternate appear. Although IBS is not fatal, it seriously affects the patients’ daily life and work. Western drug, such as antidiarrheals, gastrointestinal antispasmodic, often cannot get satisfying curative effects. However, the therapeutic effect of Traditional Chinese medicine (TCM) on IBS is very satisfactory which was shown in a large number of randomized controlled trials. Although TCM has been widely used in clinical practice, its relative effectiveness and safety have not been confirmed. Therefore, this study will use meta-analysis to verify the efficacy and safety of different types of TCM in the treatment of IBS.

Methods:

We search the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, Pubmed, Embase, Web of Science, and the Cochrane library for all randomized controlled trial of TCM for the treatment of IBS from their inception to Oct 15, 2020. Two authors will independently select studies, extract data based on predesigned inclusion and exclusion criteria. Methodological quality assessment and risk of bias will be assessed using Cochrane bias risk tool. All data analysis will be conducted using Revman5.3, WinBUGS 1.4.3, and Stata14.2 software.

Results:

This study will compare the different outcome indicators of various studies directly and indirectly, and provide a high-quality synthesis of effectiveness and safety of different TCM methods for patients with IBS. The main outcome indicators include effectiveness, remission rate (no drug symptoms), relapse rate, clinical absolute score, and relative score. Secondary outcome indicators included related adverse reactions and serum serotonin concentration.

Conclusion:

The conclusion of this systematic review will provide a high-quality evidence based on the efficacy and safety of different TCM treatment methods for IBS.

Registration number:

This study protocol has been funded through a protocol registry. The registry number is INPLASY2020100052
TWIST1 expression and clinical significance in type I endometrial cancer and premalignant lesions
Authors: Shen Junhua , Chen Qin , Li Na , Bai Xiaoxia , Wang Fenfen , Li Baohua
Published: November 2020

The aim of this study was to assess the correlation of TWIST1 expression with clinical parameters and the prognosis of type I endometrial cancer (EC).

This retrospective study enrolled 345 patients. Immunohistochemical staining was performed on 55 normal endometrium (NE) samples, 27 atypical hyperplasia (AH) samples, and 263 type I EC samples. The association between TWIST1 staining and clinical characteristics and survival was evaluated by univariate and multivariate analyses.

We found significantly higher TWIST1 expression in patients with AHs and type I ECs than NEs, but there was no significant difference between TWIST1 expression in AHs and type I ECs. Aberrant TWIST1 expression was significantly associated with clinical parameters, indicating poor prognosis and shorter patient survival. Pearsons Chi-Squared test showed that high TWIST1 expression was significantly associated with a shorter disease-free survival and overall survival. More importantly, multivariate analysis showed that high TWIST1 expression, in addition to myometrial invasion, lymph vascular space invasion, and lymph node metastasis, was an independent predictor of worse DFS in patients with type I ECs.

Our findings suggest that TWIST1 might be useful in diagnosing ECs and predicting prognosis in patients with AHs and type I ECs.
Depression and survival of breast cancer patients
Authors: Zhu Guanghui , Li Juan , Li Jie , Wang Xinmiao , Dai Minghao , Chen Jiayang
Published: November 2020

Background:

Breast cancer is the most common malignancy in women worldwide. Compared with other malignant tumors, breast cancer patients have a higher incidence of depression and other psychiatric symptoms. The purpose of this meta-analysis was to determine the association between long-term survival and depression in patients with breast cancer.

Methods:

This review will include cohort studies only. Multiple databases will be searched by 2 independent reviewers, including PubMed, EMBASE, the Cochrane Library, and PsycINFO. The language of studies should be English and Chinese, published from inception to the September 2020. Two independent reviewers will carry out literature screening, research selection and data extraction. Revman5.3 software will be used to generate funnel map, assess heterogeneity, make the subgroup analysis and complete sensitivity analysis.

Results:

This review will summarize the available evidence to determine the association between depression and survival in breast cancer patients.

Conclusion:

The results of this study will provide reference for the development of comprehensive treatment for breast cancer, and will promote further research.

PROSPERO registration number:

CRD42020202200
A clinical study on the efficacy of Yiqi Huayu Jiedu decoction for reducing the risk of postoperative recurrence and metastasis of gastric cancer
Authors: Wu Cun-En , Xue Wei-Wei , Zhuang Yu-Wen , Ding Da-Wei , Zhou Jin-Yong , Liu Shen-Lin , Wang Rui-Ping , Shu Peng
Published: November 2020

Background:

Gastric cancer (GC) is one of the top 10 malignant tumors worldwide and poses a great threat to human life and health, the prevention and treatment of which has become the focus and difficulty of medical research. With its unique advantages, traditional Chinese medicine (TCM) is widely used in the prevention and treatment of postoperative recurrence and metastasis of GC as well as the improvement of patients’ quality of life. The aim of this study is to elucidate the curative effect and the underlying mechanism of Yiqi Huayu Jiedu (YQHYJD) decoction.

Methods/design:

This is a prospective, multicenter, randomized controlled trial continuing 3 years. Two hundred ninety-eight eligible patients will be randomly divided into 2 groups, the chemotherapy combined with placebo and the chemotherapy combined with YQHYJD group at a ratio of 1:1. All patients will receive the treatment for 6 months and follow up for 3 years. The primary outcomes are disease-free survival, and 1-year, 2-year, 3-year progression-free survival rate, while the secondary outcomes are tumor makers, TCM syndrome score, quality of life score, overall chemotherapy completion rate, intestinal flora diversity test, immune function (T, B lymphocyte subsets and NK cells) test. The Security index includes blood, urine and stool routine, electrocardiogram, liver function (ALT), and renal function (BUN, Scr). All of these outcomes will be analyzed at the end of the trial.

Discussion:

This research will provide the valuable evidence for the efficacy and safety of Yiqi Huayu Jiedu decoction in postoperative GC. Furthermore, it will be helpful to form a higher level of evidence-based medical basis for TCM in the treatment of GC recurrence and metastasis.

Trial registration:

ChiCTR2000039038
Management of complex liver cystic hydatidosis: challenging benign diseases for the hepatic surgeon
Authors: Fancellu Alessandro , Perra Teresa , Vergari Dario , Vargiu Isabel , Feo Claudio F. , Cossu Maria L. , Deiana Giulia , Porcu Alberto
Published: November 2020

Hydatid cysts of the liver are benign lesions which require a wide range of surgical strategies for their treatment. We hypothesized that cysts larger than 15 cm, or compressing main vascular structures, or located in both hemilivers should be considered, as well as complicated cysts, in the category of complex hydatid cysts.

In a retrospective study including 55 patients, we evaluated the characteristics of complex hydatid cysts, and compared surgical outcomes between patients operated on for complex cysts (Complex Group) and those operated on for non-complex cysts (non-Complex Group).

In the Complex Group, 19% of patients had cysto-biliary communication with recurrent cholangitis, 9.5% had cysts eroding the diaphragm or chest wall, or communicating with the bronchial tree, 31% had cysts with contact with main vascular structures, 11.9% had multiple bilobar cysts, 14.3% had giant cysts with organ displacement, and 14.3% had a combination of the above-mentioned types. Type of surgical treatment was different between the two groups (P < .001). Additional procedures were statistically more frequent in the Complex Group (P = .02). Postoperative morbidity was higher in the Complex Group, although not in a significant manner (P = .07). Median hospital stay was longer in the Complex Group (12 vs 7 days, P < .001). No 30-day mortality occurred. Four patients (7.3%), all belonging to the Complex Group, required reoperation for postoperative complications.

Surgery for complex hydatid cysts of the liver is potentially burdened by serious complications. This kind of benign liver disease requires skill-demanding procedures and should be treated in centers with expertise in both hepato-biliary surgery and hydatid disease management.
Detection and diagnostic value of serum NSE and S100B protein levels in patients with seizures associated with mild gastroenteritis
Authors: Chen Hui , Chen Yong , Zhong Jian Min
Published: November 2020

Benign convulsions with mild gastroenteritis (CwG) and febrile seizures (FS) associated with mild gastroenteritis are 2 different diseases in the spectrum of seizures associated with mild gastroenteritis. However, specific and useful indicators for the identification of the 2 diseases are lacking. A retrospective analysis was performed to compare the serum neuronal-specific enolase (NSE) and S100B protein levels between patients with these 2 diseases to evaluate the value of NSE and S100B for differential diagnosis between these 2 diseases.

The clinical data and NSE and S100B protein levels of 81 children with seizure-associated mild gastroenteritis were collected. According to the axillary temperature at the time of convulsions, all patients were classified into an afebrile seizure (AFS) group, hereafter called the CwG group (n = 46), and a febrile seizure group (FS group, n = 35).

The serum NSE level was higher in the CwG group than in the FS group (14.046 (11.095, 19.266) pg/ml and 9.034 (7.158, 12.165) pg/ml, respectively, P < .001); however, the serum S100B protein levels in the CwG and the FS group were not significantly different (P > .05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for NSE was 0.806, P = .000, which was statistically significant. The Youden index was largest (0.605) for a serum NSE cut-off value of 10.460 pg/ml, which yielded a sensitivity and specificity of 89% and 71%, respectively, for prediction of a CwG diagnosis.

NSE may contribute to the differential diagnosis of CwG and FS associated with mild gastroenteritis.
Transformative science from the lunar farside: observations of the dark ages and exoplanetary systems at low radio frequencies
Authors: Burns Jack O.
Published: November 2020

The farside of the Moon is a pristine, quiet platform to conduct low radio frequency observations of the early Universe's Dark Ages, as well as space weather and magnetospheres associated with habitable exoplanets. In this paper, the astrophysics associated with NASA-funded concept studies will be described including a lunar-orbiting spacecraft, DAPPER, that will measure the 21 cm global spectrum at redshifts ≈40–80, and an array of low frequency dipoles on the lunar farside surface, FARSIDE, that would detect exoplanet magnetic fields. DAPPER observations (17–38 MHz), using a single cross-dipole antenna, will determine the amplitude of the 21 cm spectrum to the level required to distinguish the standard ΛCDM cosmological model from those produced by exotic physics such as nongravitational dark matter interactions. FARSIDE has a notional architecture consisting of 128 dipole antennas deployed across a 10 km area by a rover. FARSIDE would image the entire sky each minute in 1400 channels over 0.1–40 MHz. This would enable monitoring of the nearest stellar systems for the radio signatures of coronal mass ejections and energetic particle events, and would also detect the magnetospheres of the nearest candidate habitable exoplanets. In addition, FARSIDE would provide a pathfinder for power spectrum measurements of the Dark Ages.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 1)’.
German Aerospace Center's advanced robotic technology for future lunar scientific missions
Authors: Wedler Armin , Schuster Martin J. , Müller Marcus G. , Vodermayer Bernhard , Meyer Lukas , Giubilato Riccardo , Vayugundla Mallikarjuna , Smisek Michal , Dömel Andreas , Steidle Florian , Lehner Peter , Schröder Susanne , Staudinger Emanuel , Foing Bernard , Reill Josef
Published: November 2020

The Earth's moon is currently an object of interest of many space agencies for unmanned robotic missions within this decade. Besides future prospects for building lunar gateways as support to human space flight, the Moon is an attractive location for scientific purposes. Not only will its study give insight on the foundations of the Solar System but also its location, uncontaminated by the Earth's ionosphere, represents a vantage point for the observation of the Sun and planetary bodies outside the Solar System. Lunar exploration has been traditionally conducted by means of single-agent robotic assets, which is a limiting factor for the return of scientific missions. The German Aerospace Center (DLR) is developing fundamental technologies towards increased autonomy of robotic explorers to fulfil more complex mission tasks through cooperation. This paper presents an overview of past, present and future activities of DLR towards highly autonomous systems for scientific missions targeting the Moon and other planetary bodies. The heritage from the Mobile Asteroid Scout (MASCOT), developed jointly by DLR and CNES and deployed on asteroid Ryugu on 3 October 2018 from JAXA's Hayabusa2 spacecraft, inspired the development of novel core technologies towards higher efficiency in planetary exploration. Together with the lessons learnt from the ROBEX project (2012–2017), where a mobile robot autonomously deployed seismic sensors at a Moon analogue site, this experience is shaping the future steps towards more complex space missions. They include the development of a mobile rover for JAXA's Martian Moons eXploration (MMX) in 2024 as well as demonstrations of novel multi-robot technologies at a Moon analogue site on the volcano Mt Etna in the ARCHES project. Within ARCHES, a demonstration mission is planned from the 14 June to 10 July 2021,
1
during which heterogeneous teams of robots will autonomously conduct geological and mineralogical analysis experiments and deploy an array of low-frequency antennas to measure Jovian and solar bursts.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 1)'.
Low-frequency technology for a lunar interferometer
Authors: Adami Kristian Zarb , Farhat I. O.
Published: November 2020

This work sketches a possible design architecture of a low-frequency radio interferometer located on the lunar surface. The design has evolved from single antenna experiments aimed at the global signal detection of the epoch of reionization (EoR) to the square kilometre array (SKA) which, when complete, will be capable of imaging the highly red-shifted H
1
-signal from the cosmic dawn through to the EoR. However, due to the opacity of the ionosphere below 10 MHz and the anthropogenic radio-frequency interference, these terrestrial facilities are incapable of detecting pre-ionization signals and the moon becomes an attractive location to build a low-frequency radio interferometer capable of detecting such cosmological signals. Even though there are enormous engineering challenges to overcome, having this scientific facility on the lunar surface also opens up several new exciting possibilities for low-frequency radio astronomy.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 1)’.
LOUPE: observing Earth from the Moon to prepare for detecting life on Earth-like exoplanets
Authors: Klindžić D. , Stam D. M. , Snik F. , Keller C. U. , Hoeijmakers H. J. , van Dam D. M. , Willebrands M. , Karalidi T. , Pallichadath V. , van Dijk C. N. , Esposito M.
Published: November 2020

LOUPE, the Lunar Observatory for Unresolved Polarimetry of the Earth, is a small, robust spectro-polarimeter for observing the Earth as an exoplanet. Detecting Earth-like planets in stellar habitable zones is one of the key challenges of modern exoplanetary science. Characterizing such planets and searching for traces of life requires the direct detection of their signals. LOUPE provides unique spectral flux and polarization data of sunlight reflected by Earth, the only planet known to harbour life. These data will be used to test numerical codes to predict signals of Earth-like exoplanets, to test algorithms that retrieve planet properties, and to fine-tune the design and observational strategies of future space observatories. From the Moon, LOUPE will continuously see the entire Earth, enabling it to monitor the signal changes due to the planet’s daily rotation, weather patterns and seasons, across all phase angles. Here, we present both the science case and the technology behind LOUPE’s instrumental and mission design.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 1)’.
Pantheon habitat made from regolith, with a focusing solar reflector
Authors: Woolf Nick , Angel Roger
Published: November 2020

We describe a polar Moon base habitat using direct solar energy for construction, food production and atmospheric revitalization. With a growing area as large as 2000 m
2
, it could provide for 40 or more people. The habitat is built like the ancient Roman Pantheon, a stone structure with a top circular oculus, bringing in focused sunlight that is spread out to crops below. The conical, corbelled structure is built from cast regolith blocks, held in compression despite the large internal atmospheric pressure by a regolith overlayer 20–30 m thick. It is sealed on the inside against leaks with thin plastic. A solar mirror concentrator used initially to cast the building blocks is later used to illuminate the habitat through a small pressure window at the oculus. Three years of robotic preparation of the building blocks does not seem excessive for a habitat which can be expected to last for millennia, as has the Treasury of Atreus made by similar dry-stone construction. One goal of returning to the Moon is to demonstrate the practicality of long-term human habitation off the Earth. The off-axis, paraboloidal reflecting mirror is rotated about the vertical polar axis in order to direct horizontal sunlight downward to a focus. In this way, the heavy materials needed from Earth to build and power the habitat are largely limited to the solar concentrator and regolith moving and moulding equipment. By illuminating with a reflector rather than with electricity, the solar collection area is 20 times smaller than would be needed for PV cells.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 1)’.
Poor in-utero growth, and reduced beta cell compensation and high fasting glucose from childhood, are harbingers of glucose intolerance in young Indians
Authors: Yajnik Chittaranjan S , Bandopadhyay Souvik , Bhalerao Aboli , Bhat Dattatray S , Phatak Sanat B , Wagh Rucha H , Yajnik Pallavi C , Pandit Anand , Bhave Sheila , Coyaji Kurus , Kumaran Kalyanaraman , Osmond Clive , Fall Caroline HD
Published: November 2020

Objective

India is a double world capital for early life undernutrition and type 2 diabetes. We aimed to characterise lifecourse growth and metabolic trajectories in those developing glucose intolerance as young adults, in the Pune Maternal Nutrition Study (PMNS).

Research design and Methods

PMNS is a community-based intergenerational birth cohort established in 1993, with serial information on parents and children through pregnancy, childhood and adolescence. We compared normal glucose tolerant and glucose intolerant participants for serial growth, estimates of insulin sensitivity and secretion (HOMA and dynamic indices) and beta cell compensation accounting for prevailing insulin sensitivity (disposition index).

Results

At 18 years (N=619) 37% men and 20% women were glucose intolerant (184 prediabetes, 1 diabetes) despite 48% being underweight (BMI<18.5 kg/m2). Glucose intolerant participants had higher fasting glucose from childhood. Mothers of glucose intolerant participants had higher glycemia in pregnancy. Glucose intolerant participants were shorter at birth. Insulin sensitivity decreased with age in all participants, and the glucose intolerant had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had a 2.5- and 4.0-fold higher risk respectively of 18-year glucose intolerance; this finding was replicated in two other cohorts.

Conclusion

Inadequate compensatory insulin secretory response to increasing insulin insensitivity from early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia in childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.
Outbreaks of publications about emerging infectious diseases: the case of SARS-CoV-2 and Zika virus
Authors: Ipekci Aziz Mert , Buitrago-Garcia Diana , Meili Kaspar Walter , Krauer Fabienne , Prajapati Nirmala , Thapa Shabnam , Wildisen Lea , Chaveron Lucia Araujo , Baumann Lukas , Shah Sanam , Whiteley Tessa , Solís-García Gonzalo , Tsotra Foteini , Zhelyazkov Ivan , Imeri Hira , Low Nicola , Counotte Michel Jacques
Published: November 2020

Background

Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 epidemics of Zika virus emerged, largely in Latin America and the Caribbean. In 2020, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of coronavirus disease 2019 (COVID-19). We compared patterns of scientific publications for the two infections over time.

Methods

We used living systematic review methods to search for and annotate publications according to study design. For Zika virus, a review team performed the tasks for publications in 2016. For SARS-CoV-2, a crowd of 25 volunteer scientists performed the tasks for publications up to May 24, 2020. We used descriptive statistics to categorise and compare study designs over time.

Findings

We found 2,286 publications about Zika virus in 2016 and 21,990 about SARS-CoV-2 up to 24 May 2020, of which we analysed a random sample of 5294. For both infections, there were more epidemiological than laboratory science studies. Amongst epidemiological studies for both infections, case reports, case series and cross-sectional studies emerged first, cohort and case-control studies were published later. Trials were the last to emerge. Mathematical modelling studies were more common in SARS-CoV-2 research. The number of preprints was much higher for SARS-CoV-2 than for Zika virus.

Interpretation

Similarities in the overall pattern of publications might be generalizable, whereas differences are compatible with differences in the characteristics of a disease. Understanding how evidence accumulates during disease outbreaks helps us understand which types of public health questions we can answer and when.

Funding

MJC and HI are funded by the Swiss National Science Foundation (SNF grant number 176233). NL acknowledges funding from the European Union’s Horizon 2020 research and innovation programme - project EpiPose (grant agreement number 101003688). DBG is funded by the Swiss government excellence scholarship (2019.0774) and the Swiss School of Public Health Global P3HS.
Coagulation factors and COVID-19 severity: Mendelian randomization analyses and supporting evidence
Authors: Zhou Yao , Liu Zipeng , Yang Hongxi , Wang Jianhua , Liu Tong , Chen Kexin , Wang Yaogang , Sham Pak Chung , Yu Ying , Li Mulin Jun
Published: November 2020

Background

The evolving pandemic of COVID-19 is arousing alarm to public health. According to epidemiological and observational studies, coagulopathy was frequently seen in severe COVID-19 patients, yet the causality from specific coagulation factors to COVID-19 severity and the underlying mechanism remain elusive.

Methods

First, we leveraged Mendelian randomization (MR) analyses to assess causal relationship between 12 coagulation factors and severe COVID-19 illness based on two genome-wide association study (GWAS) results of COVID-19 severity. Second, we curated clinical evidence supporting causal associations between COVID-19 severity and particular coagulation factors which showed significant results in MR analyses. Third, we validated our results in an independent cohort from UK Biobank (UKBB) using polygenic risk score (PRS) analysis and logistic regression model. For all MR analyses, GWAS summary-level data were used to ascertain genetic effects on exposures against disease risk.

Results

We revealed that genetic predisposition to the antigen levels of von Willebrand factor (VWF) and the activity levels of its cleaving protease ADAMTS13 were causally associated with COVID-19 severity, wherein elevated VWF antigen level (P = 0.005, odds ratio (OR) = 1.35, 95% confidence interval (CI): 1.09-1.68 in the Severe COVID-19 GWAS Group cohort; P = 0.039, OR = 1.21, 95% CI: 1.01-1.46 in the COVID-19 Host Genetics Initiative cohort) and lowered ADAMTS13 activity (P = 0.025, OR = 0.69, 95% CI: 0.50-0.96 in the Severe COVID-19 GWAS Group cohort) lead to increased risk of severe COVID-19 illness. No significant causal association of tPA, PAI-1, D-dimer, FVII, PT, FVIII, FXI, aPTT, FX or ETP with COVID-19 severity was observed. In addition, as an independent factor, VWF PRS explains a 31% higher risk of severe COVID-19 illness in the UKBB cohort (P = 0.047, OR per SD increase = 1.31, 95% CI: 1.00-1.71). In combination with age, sex, BMI and several pre-existing disease statues, our model can predict severity risks with an AUC of 0.70.

Conclusion

Together with the supporting evidence of recent retrospective cohort studies and independent validation based on UKBB data, our results suggest that the associations between coagulation factors VWF/ADAMTS13 and COVID-19 severity are essentially causal, which illuminates one of possible mechanisms underlying COVID-19 severity. This study also highlights the importance of dynamically monitoring the plasma levels of VWF/ADAMTS13 after SARS-CoV-2 infection, and facilitates the development of treatment strategy for controlling COVID-19 severity and associated thrombotic complication.
Blood pressure variability and night-time dipping assessed by 24-hour ambulatory monitoring: cross-sectional association with cardiac structure in adolescents
Authors: Goudswaard Lucy , Harrison Sean , Van De Klee Daniel , Chaturvedi Nishi , Lawlor Debbie , Smith George Davey , Hughes Alun , Howe Laura D
Published: November 2020

Greater blood pressure (BP) variability and reduced night-time BP dipping are associated with cardiovascular disease risk independently of mean BP in adults. This study examines whether these associations are apparent in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) left ventricular mass indexed to height2.7 (LVMi2.7); 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. In this general adolescent population study, associations between BP variability and cardiac structure were apparent. Measurement of BP variability might benefit cardiovascular risk assessment in adolescents.
ThinkCancer! The multi-method development of a complex behaviour change intervention to improve the early diagnosis of cancer in primary care
Authors: Surgey Alun , Disbeschl Stefanie , Lewis Ruth , Hiscock Julia , Nafees Sadia , Law Rebecca J , Roberts Jessica L , Hendry Annie , Hoare Zoe , Goulden Nia , Stanciu Marian A , Carson-Stevens Andrew , Smits Stephanie , Brain Kate , Edwards Rhiannon T , Williams Nefyn , Neal Richard D , Wilkinson Clare
Published: November 2020

Background

Relatively poor UK cancer outcomes are blamed upon late diagnosis. Despite most cancer patients presenting to their GP with symptoms, diagnostic delay remains a common theme, with many clinical and non-clinical factors responsible. Early diagnosis is key to improving outcomes and survival. This paper reports the multi-method process to design a complex intervention to improve the timely diagnosis of symptomatic cancer.

Methods

A review of reviews, survey, discrete choice experiment, qualitative interviews and focus groups, all informed a realist evidence synthesis. This in turn informed the design of a complex intervention, guided by the Behaviour Change Wheel framework using a multi-step process.

Results

Key themes from the realist evidence synthesis included effective safety netting at practitioner and practice system level, increased vigilance and lowering referral thresholds. Qualitative findings explored the tensions, barriers and facilitators affecting suspected cancer referral. The Think Cancer! intervention is an educational and quality improvement workshop directed at the whole primary care team. Bespoke cancer safety netting plans and appointment of cancer champions are key components.

Conclusions

Think Cancer! is a novel primary care early cancer diagnosis intervention, requiring evaluation through a cluster randomised control trial.
The Impact of Late-Career Job Loss and Genotype on Body Mass Index
Authors: Schmitz Lauren L. , Goodwin Julia , Miao Jiacheng , Lu Qiongshi , Conley Dalton
Published: November 2020

Unemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G x E) interplay, we interacted layoffs from business closures—a plausibly exogenous environmental exposure—with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.