bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerometer-measured versus self-reported physical activity levels in women before and up to 48 months after Roux-en-Y Gastric Bypass
Authors: Possmark Sofie , Sellberg Fanny , Willmer Mikaela , Tynelius Per , Persson Margareta , Berglind Daniel
Published: February 2020

Background

Roux-en-Y Gastric Bypass (RYGB) patients overestimate their time spent in moderate-to-vigorous physical activity (MVPA) to a greater extent post-surgery than pre-surgery. However, there is no data on discrepancy between self-reported and accelerometer-measured MVPA beyond nine months post-RYGB. The aim was to investigate how the duration of MVPA (main outcome) differs when comparing a self-administered questionnaire to accelerometer-data from pre-surgery and up to 48 months post-RYGB.

Methods

Twenty-six (38%) RYGB-treated women with complete data from the original cohort (N = 69) were included. Participants were recruited from five Swedish hospitals. Mean pre-surgery BMI was 38.9 (standard deviation (SD) = 3.4) kg/m2 and mean age 39.9 (SD = 6.5) years. MVPA was subjectively measured by a self-administered questionnaire and objectively measured by the ActiGraph GT3X+ accelerometer at 3 months pre-RYGB and 9- and 48 months post-RYGB. Means and SD were calculated at 3 months pre- and 9- and 48 months post-RYGB. We calculated the P-values of the differences with Wilcoxon Signed-Rank test. For correlations between the self-administered questionnaire and the accelerometers, Spearman’s rank correlation was used.

Results

Participants significantly overestimated (i.e. self-reported more time spent in MVPA compared to accelerometry) their MVPA in a higher degree post- compared to pre-RYGB surgery. Compared to pre-surgery, self-reported MVPA increased with 46.9 and 36.5% from pre- to 9- and 48 months, respectively, whereas changes were a 6.1% increase and 3.5% decrease with accelerometers. Correlations between self-reported and accelerometer-measured MVPA-assessments were poor at all measurement points (r = 0.21–0.42) and only significant at 48 months post-RYGB (P = 0.032).

Conclusions

The discrepancy between self-reported and objectively assessed MVPA within the same individual is greater up to 48 months post-RYGB compared to before surgery. To help bariatric patients understand and hopefully increase their physical activity behaviors post-surgery, objective measures of physical activity should be used.
Do partial AZFc deletions affect the sperm retrieval rate in non-mosaic Klinefelter patients undergoing microdissection testicular sperm extraction?
Authors: Huang I-Shen , Fantus Richard J. , Chen Wei-Jen , Wren James , Kao Wei-Tang , Huang Eric Yi-Hsiu , Bennett Nelson E. , Brannigan Robert E. , Huang William J.
Published: February 2020

Background

The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects on spermatogenesis in non-mosaic Klinefelter patients. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed.

Methods

We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery.

Results

Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3, one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p = 0.27).

Conclusion

According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.
The impact of conventional and organic farming on soil biodiversity conservation: a case study on termites in the long-term farming systems comparison trials in Kenya
Authors: Anyango John J. , Bautze David , Fiaboe Komi K. M. , Lagat Zipporah O. , Muriuki Anne W. , Stöckli Sibylle , Riedel Judith , Onyambu Gladys K. , Musyoka Martha W. , Karanja Edward N. , Adamtey Noah
Published: February 2020

Background

A long-term experiment at two trial sites in Kenya has been on-going since 2007 to assess the effect of organic and conventional farming systems on productivity, profitability and sustainability. During these trials the presence of significant numbers of termites (Isoptera) was observed. Termites are major soil macrofauna and within literature they are either depict as ‘pests’ or as important indicator for environmental sustainability. The extent by which termites may be managed to avoid crop damage, but improve sustainability of farming systems is worthwhile to understand. Therefore, a study on termites was added to the long-term experiments in Kenya. The objectives of the study were to quantify the effect of organic (Org) and conventional (Conv) farming systems at two input levels (low and high) on the abundance, incidence, diversity and foraging activities of termites.

Results

The results showed higher termite abundance, incidence, activity and diversity in Org-High compared to Conv-High, Conv-Low and Org-Low. However, the termite presence in each system was also dependent on soil depth, trial site and cropping season. During the experiment, nine different termite genera were identified, that belong to three subfamilies: (i)Macrotermitinae(genera:Allodontotermes,Ancistrotermes,Macrotermes,Microtermes,OdontotermesandPseudocanthotermes), (ii)Termitinae(AmitermesandCubitermes) and (iii)Nasutitiermitinae(Trinervitermes).

Conclusions

We hypothesize that the presence of termites within the different farming systems might be influenced by the types of input applied, the soil moisture content and the occurrence of natural enemies. Our findings further demonstrate that the organic high input system attracts termites, which are an important, and often beneficial, component of soil fauna. This further increases the potential of such systems in enhancing sustainable agricultural production in Kenya.
Short and long-term metabolic outcomes in patients with type 1 and type 2 diabetes receiving a simultaneous pancreas kidney allograft
Authors: Hau Hans-Michael , Jahn Nora , Brunotte Maximilian , Lederer Andri Arnosson , Sucher Elisabeth , Rasche Franz Maximilian , Seehofer Daniel , Sucher Robert
Published: February 2020

Background

In contrast to insulin-dependent type 1 diabetes mellitus (T1DM), the indication for Simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) is still ambiguous and wisely Eurotransplant (ET) only granted transplant-permission in a selected group of patients. However, with regard to improvement of metabolic conditions SPK might still be a considerable treatment option for lean insulin dependent type 2 diabetics suffering from renal disease.

Methods

Medical data (2001–2013) from all consecutive T1DM and T2DM patients who received a SPK or kidney transplant alone (KTA) at the University Hospital of Leipzig were analyzed. Donor, recipients and long-term endocrine, metabolic and graft outcomes were investigated for T1DM and T2DM-SPK recipients (transplanted upon a special request allocation by ET) and T2DM patients who received a KTA during the same period.

Results

Eighty nine T1DM and 12 T2DM patients received a SPK and 26 T2DM patients received a KTA. Patient survival at 1 and 5 years was 89.9 and 88.8% for the T1DM group, 91.7 and 83.3% for the T2DM group, and 92.3 and 69.2% for the T2DM KTA group, respectively (p < 0.01). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was 83.1 and 78.7% for the T1DM group and 91.7 and 83.3% for the T2DM group, respectively (p = 0.71). Kidney allograft survival at 5 years was 79.8% for T1DM, 83.3% for T2DM, and 65.4% for T2DM KTA (p < 0.01). Delayed graft function (DGF) rate was significantly higher in type 2 diabetics received a KTA. Surgical, immunological and infectious complications showed similar results for T1DM and T2DM recipients after SPK transplant and KTA, respectively. With regard to the lipid profile, the mean high-density lipoprotein (HDL)- cholesterol levels were significantly higher in T1DM recipients compared to T2DM patients before transplantation (p = 0.02) and remained significantly during follow up period.

Conclusion

Our data demonstrate that with regard to metabolic function a selected group of patients with T2DM benefit from SPK transplantation. Consensus guidelines and further studies for SPK transplant indications in T2DM patients are still warranted.
A modular pathway engineering strategy for the high-level production of β-ionone in Yarrowia lipolytica
Authors: Lu Yanping , Yang Qingyu , Lin Zhanglin , Yang Xiaofeng
Published: February 2020

Background

The GRAS and oleaginous yeast Yarrowia lipolytica (Y. lipolytica) is an attractive cell factory for the production of chemicals and biofuels. The production of many natural products of commercial interest have been investigated in this cell factory by introducing heterologous biosynthetic pathways and by modifying the endogenous pathways. However, since natural products anabolism involves long pathways and complex regulation, re-channelling carbon into the product of target compounds is still a cumbersome work, and often resulting in low production performance.

Results

In this work, the carotenogenic genes contained carB and bi-functional carRP from Mucor circinelloides and carotenoid cleavage dioxygenase 1 (CCD1) from Petunia hybrida were introduced to Y. lipolytica and led to the low production of β-ionone of 3.5 mg/L. To further improve the β-ionone synthesis, we implemented a modular engineering strategy for the construction and optimization of a biosynthetic pathway for the overproduction of β-ionone in Y. lipolytica. The strategy involved the enhancement of the cytosolic acetyl-CoA supply and the increase of MVA pathway flux, yielding a β-ionone titer of 358 mg/L in shake-flask fermentation and approximately 1 g/L (~ 280-fold higher than the baseline strain) in fed-batch fermentation.

Conclusions

An efficient β-ionone producing GRAS Y. lipolytica platform was constructed by combining integrated overexpressed of heterologous and native genes. A modular engineering strategy involved the optimization pathway and fermentation condition was investigated in the engineered strain and the highest β-ionone titer reported to date by a cell factory was achieved. This effective strategy can be adapted to enhance the biosynthesis of other terpenoids in Y. lipolytica.
Modified PCR-based assay for the differentiation of members of Anopheles fluviatilis complex in consequence of the discovery of a new cryptic species (species V)
Authors: Singh Om P. , Nanda Nutan , Chandra Dinesh , Jha Deepa , Adak Tridibes , Dua Virendra K. , Subbarao Sarala K.
Published: February 2020

Background

Anopheles fluviatilis is a species-complex comprising of four cryptic species provisionally designated as species S, T, U and V. Earlier, a 28S-rDNA based allele-specific polymerase chain reaction (ASPCR) assay was developed for the differentiation of the then known three members of the An. fluviatilis complex, i.e., species S, T, and U. This assay was modified in consequence of the discovery of a new cryptic member, species V, in the Fluviatilis Complex to include identification of new species.

Methods

In the modified procedure, the ASPCR assay was performed first, followed by restriction digestion of PCR product with an enzyme BamH I, which cleaves specifically PCR amplicon of species V and the resultant PCR–RFLP products can differentiate all the four cryptic members of the complex. Morphologically identified An. fluviatilis samples were subjected to sibling species identification by modified PCR-based assay and standard cytotaxonomy. The result of PCR-based assay was validated through cytotaxonomy as well as DNA sequencing of some representative samples.

Results

The modified PCR-based assay differentiates all four sibling species. The result of modified PCR-based assay tested on field samples was in agreement with results of cytotaxonomy as well as DNA sequencing of representative samples.

Conclusions

The modified PCR-based assay unambiguously differentiates all four known members of the An. fluviatilis species complex. This assay will be useful in studies related to bionomics of members of the Fluviatilis Complex in their role in malaria transmission.
Characterization of novel LncRNA P14AS as a protector of ANRIL through AUF1 binding in human cells
Authors: Ma Wanru , Qiao Juanli , Zhou Jing , Gu Liankun , Deng Dajun
Published: February 2020

Background

The CDKN2A/B locus contains crucial tumor suppressors and a lncRNA gene ANRIL. However, the mechanisms that coordinately regulate their expression levels are not clear.

Methods

Novel RNAs transcribed from the CDKN2A gene were screened by CDKN2A-specific RNA capture deep-sequencing and confirmed by Northern blotting and clone-sequencing. Long non-coding RNA (lncRNA) binding proteins were characterized by RNA pull-down combined with mass spectrometry and RNA immunoprecipitation. LncRNA functions in human cells were studied using a set of biological assays in vitro and in vivo.

Results

We characterized a novel lncRNA, P14AS with its promoter in the antisense strand of the fragment near CDKN2A exon 1b in human cells. The mature P14AS is a three-exon linear cytoplasmic lncRNA (1043-nt), including an AU-rich element (ARE) in exon 1. P14AS decreases AUF1-ANRIL/P16 RNA interaction and then increases ANRIL/P16 expression by competitively binding to AUF1 P37 and P40 isoforms. Interestingly, P14AS significantly promoted the proliferation of cancer cells and tumor formation in NOD-SCID mice in a P16-independent pattern. Moreover, in human colon cancer tissues, the expression levels of P14AS and ANRIL lncRNAs were significantly upregulated compared with the paired normal tissues.

Conclusion

A novel lncRNA, P14AS, transcribed from the antisense strand of the CDKN2A/P14 gene, promotes colon cancer development by cis upregulating the expression of oncogenic ANRIL.
The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression
Authors: Wu Yuqing , Zhang Siwei , Gong Xiaoxiao , Tam Samantha , Xiao Desheng , Liu Shuang , Tao Yongguang
Published: February 2020

Ferroptosis, a novel form of regulated cell death, is different from other types of cell death in morphology, genetics and biochemistry. Increasing evidence indicates that ferroptosis has significant implications on cell death linked to cardiomyopathy, tumorigenesis, and cerebral hemorrhage to name a few. Here we summarize current literature on ferroptosis, including organelle dysfunction, signaling transduction pathways, metabolic reprogramming and epigenetic regulators in cancer progression. With regard to organelles, mitochondria-induced cysteine starvation, endoplasmic reticulum-related oxidative stress, lysosome dysfunction and golgi stress-related lipid peroxidation all contribute to induction of ferroptosis. Understanding the underlying mechanism in ferroptosis could provide insight into the treatment of various intractable diseases including cancers.
CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis
Authors: Yang Hui , Zhang Qiannan , Xu Miao , Wang Lei , Chen Xuewei , Feng Yongquan , Li Yongning , Zhang Xin , Cui Wenming , Jia Xudong
Published: February 2020

Background

The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for cancer treatment, mechanisms underlying its infiltration, activation and tumor-promotive function in ESCC remain unknown.

Methods

Human esophageal tissue array and TCGA database were used to evaluate the clinical relevance of CCL2 and TAMs in ESCC. F344 rats and C57BL/6 mice were treated with N-nitrosomethylbenzylamine (NMBA) to establish orthotopic models of esophageal carcinogenesis. CCL2/CCR2 gene knockout mice and macrophage-specific PPARG gene knockout mice were respectively used to investigate the role of infiltration and polarization of TAMs in ESCC. CCL2-mediated monocyte chemotaxis was estimated in malignantly transformed Het-1A cells. THP-1 cells were used to simulate TAMs polarization in vitro. RNA-sequencing was performed to uncover the mechanism.

Results

Increasing expression of CCL2 correlated with TAMs accumulation in esophageal carcinogenesis, and they both predicts poor prognosis in ESCC cohort. Animal studies show blockade of CCL2-CCR2 axis strongly reduces tumor incidence by hindering TAMs recruitment and thereby potentiates the antitumor efficacy of CD8+ T cells in the tumor microenvironment. More importantly, M2 polarization increases PD-L2 expression in TAMs, resulting in immune evasion and tumor promotion through PD-1 signaling pathway.

Conclusion

This study highlights the role of CCL2-CCR2 axis in esophageal carcinogenesis. Our findings provide new insight into the mechanism of immune evasion mediated by TAMs in ESCC, suggesting the potential of TAMs-targeted strategies for ESCC prevention and immunotherapy.
CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer
Authors: Zhang Haiyang , Deng Ting , Liu Rui , Ning Tao , Yang Haiou , Liu Dongying , Zhang Qiumo , Lin Dan , Ge Shaohua , Bai Ming , Wang Xinyi , Zhang Le , Li Hongli , Yang Yuchong , Ji Zhi , Wang Hailong , Ying Guoguang , Ba Yi
Published: February 2020

Background

Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic.

Methods

Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential.

Results

Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity.

Conclusions

The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC.

Graphical abstract
The effect of medical insurance on catastrophic health expenditure: evidence from China
Authors: Sun Jian , Lyu Shoujun
Published: February 2020

Background

The Chinese government has established a nationwide multiple-level medical insurance system. However, catastrophic health expenditure (CHE) causes great harm to the quality of life of households and pushes them into poverty. The objective of this paper is to assess the effect of medical insurance on CHE in China and compare the financial protection effects of different medical insurances.

Methods

Panel data were obtained from China Family Panel Studies (CFPS) conducted in the years of 2012, 2014, and 2016. CHE incidence was measured by performing a headcount, and its intensity was estimated using overshoot and mean positive overshoot (MPO). In addition, concentration index (CI) was used to measure the degree of socioeconomic inequality of CHE occurrence. Furthermore, random effects panel Probit regression model was employed to assess the effect of medical insurance on CHE. Lastly, random effects panel Logit regression model was adopted to perform a robustness check.

Results

From 2012 to 2016, the total CHE incidence jumped from 15.05% to 15.24%, and the CI in CHE changed from − 0.0076 to − 0.1512. Moreover, the total overshoot increased from 0.0333 to 0.0344, while the total MPO grew from 0.2213 to 0.2257. Furthermore, the global regression results show that residents covered by Supplementary Medical Insurance (SMI) were linked to a decreased probability of experiencing CHE. In addition, the regression results by gender indicate that SMI coverage for male residents had a significant effect on the prevention of CHE, while the effect was not significant for female residents. The regression results by health status show that SMI had a significant impact on reducing the likelihood of CHE occurrence for healthy residents, whilst the impact was not significant for unhealthy residents. Lastly, the robustness check results were consistent with those of previous findings.

Conclusion

The results of this study suggest that CHE incidence and intensity became relatively higher among households. In addition, CHE occurrence was concentrated among the poorer households and the equality status worsened. Moreover, financial protection effects of the four medical insurance schemes against CHE varied significantly. Furthermore, the protection effect of SMI against CHE shows significant gender and health status disparities.
Uniportal VATS right superior lobectomy: management of pulmonary vein variation: a case report
Authors: Wang Zhao , Sun Yungang , Zhang Qiang , Shao Feng
Published: February 2020

Background

Although there are lots of variations of pulmonary veins including dangerous type that could cause serious complications during surgery, limited information has been reported about these variations. We have experienced an extremely rare anomaly of the right superior pulmonary vein during right superior lobectomy. We used a technique called “non fissure” to manage the right superior pulmonary vein, and the results were satisfactory.

Case presentation

A 66-year-old woman with lung nodules visited our hospital. Chest computed tomography revealed multiple ground glass nodules in the right lung, the main pulmonary nodule was 11 mm in diameter and presented mixed density. The patient had a previous history of rectal cancer surgery. Contrast-enhanced three-dimensional computed tomography showed that the right superior pulmonary vein abnormally ran between the pulmonary artery trunk and the right main bronchus. We performed a right superior lobectomy and lymph node sampling by uniportal video-assisted thoracoscopic surgery. The pathological findings showed microinvasive adenocarcinoma with no lymphatic metastasis. She was discharged 7 days after surgery without any surgical complications.

Conclusions

Although the variation of pulmonary vein is uncommon, it is dangerous to misidentify in the operation. Preoperative three-dimensional computed tomography is useful for avoiding unexpected bleeding. The technique “no fissure” might be a useful way to manage the variation of pulmonary vein.
A civil society view of rare disease public policy in six Latin American countries
Authors: Mayrides Mo , Ruiz de Castilla Eva Maria , Szelepski Silvina
Published: February 2020

Patients with rare diseases across the world struggle to access timely diagnosis and state-of-the-art treatment and management of their conditions. Several recently published reviews highlight the importance of country efforts to address rare diseases and orphan drugs policy comprehensively. However, many of these reviews lack depth and detail at the local level, which we believe is necessary for rare disease advocates to identify and prioritize opportunities for strengthening each country’s policy framework.

We asked leading patient advocates from civil society organizations their views on rare disease public policy in Argentina, Brazil, Chile, Colombia, Mexico, and Peru with a focus on whether specific laws and regulations in these six Latin American countries have been promulgated. From December 2018 to March 2019 we supplemented their perspectives with evidence from accessible literature using key search terms. For each country, we prepared a detailed analysis on how laws or other policy initiatives took shape and the steps taken since to implement them. This allowed us to identify five broad policy categories for subsequent analysis: national laws, national regulations, health system incorporation of rare disease treatments, care delivery, and patient engagement.

By describing the different approaches, challenges and timelines across six countries, our research demonstrates that strengthening rare disease policy first requires a common understanding and local consensus of each country’s recent past and current situation. Subsequent analysis based on a set of common policy dimensions led us to where we believe salient opportunities lie for each of these countries to strengthen their overall policy framework for rare disease patients.
Responding to the challenge of Adolescent Perinatal Depression (RAPiD): protocol for a cluster randomized hybrid trial of psychosocial intervention in primary maternal care
Authors: Gureje Oye , Kola Lola , Oladeji Bibilola D. , Abdulmalik Jibril , Ayinde Olatunde , Zelkowitz Phyllis , Bennett Ian
Published: February 2020

Background

Adolescent pregnancy is a pressing public health issue globally, and particularly in low and middle-income countries. Depression occurring in the perinatal period is common among women and more so among adolescent mothers. Effective treatments for the condition have been demonstrated in adults but the needs of adolescents are often unique, making such treatments unlikely to meet those needs.

Method/study design

A hybrid effectiveness–implementation research study is described in which a cluster randomized trial design is used to explore the effectiveness as well as the utility in routine practice of an intervention package specifically designed for adolescents with perinatal depression. Consenting pregnant adolescents (aged less than 20 years) who are newly registered for antenatal care are enrolled into the trial if their fetal gestational age is less than 36 weeks and they score 12 or more on the Edinburgh Postnatal Depression Scale (EPDS). The intervention package consists of structured sessions of behavior activation, problem-solving treatment, and parenting skills training, and is delivered by primary maternal health care providers, complemented by support provided by a “neighborhood mother” identified by the adolescent. Mothers in the control arm receive care as usual. The trial is conducted in clinics where the maternal providers are trained to deliver routine depression care with the use of the WHO Mental Health Gap Action Programme, intervention guide. Assessments are undertaken by trained blinded assessors at baseline, at childbirth, and at 3 and 6 months postpartum. The primary outcome, assessed at 6 months, is the level of maternal depression (measured with the EPDS). The secondary outcome is parenting skills (assessed with the Home Observation Measurement of the Environment, Infant–Toddler version), while tertiary outcomes include measures of disability, quality of life, mother–child bonding, as well as infants’ nutritional and growth indices.

Discussion

This, to the best of our knowledge, will be the first fully-powered trial of an intervention package specifically designed to address the unique needs of adolescents with perinatal depression.

Trial registration

ISRCTN16775958. Registered on 30 April 2019.
Comparison of the clinical benefits for non-small cell lung cancer patients between different volume of pleural lavage fluid following video-assisted thoracoscopic lobectomy and systematic mediastinal lymph node dissection: study protocol for a randomized controlled trial
Authors: Zhou Jian , Liu Chengwu , Man Shulei , Lyu Mengyuan , Liao Hu , Chen Nan , Cheng Yuhui , Liu Lunxu
Published: February 2020

Background

Pleural lavage is regularly performed before closing the chest wall in pulmonary surgeries to prevent pleural implantation of tumor cells and postoperative infection. However, scant data could be found in the literature regarding the optimal regimen for performing pleural lavage. To establish a proper volume of pleural lavage, we herein designed a protocol for a randomized controlled trial.

Methods

A total of 400 participants with non-small cell lung cancer undergoing video-assisted thoracoscopic surgery (VATS) lobectomy and systematic mediastinal lymph node dissection (MLND) will be randomly assigned to one of two groups: group A (500 mL pleural lavage fluid) and group B (3000 mL pleural lavage fluid). The primary outcomes include the levels of leukocytes, neutrophils, and inflammatory factors on the first postoperative day. The secondary outcomes include (i) the levels of leukocytes, neutrophils, and inflammatory factors on the second and third postoperative days; (ii) the incidence of postoperative fever on the first, second, and third postoperative days; (iii) the volumes of chest drainage within the first 3 operative days, the duration of drainage, and postoperative hospitalization; and (iv) the incidence of postoperative complications (incision infection, pain, atelectasis, hemorrhage, etc.) and the incidence of pleural effusion requiring thoracic puncture or drainage within 30 days after surgery. The main content of the analysis includes effectiveness and safety analysis. We will perform subgroup analyses to identify potential influence factors.

Discussion

As far as we know, this will be the first randomized controlled trial to compare the clinical outcomes between different volumes of pleural lavage fluid following VATS and MLND. Findings from this trial will determine the appropriate amount of pleural lavage before chest wall closure.

Trial registration

This study was registered with the Chinese Clinical Trial Registry ( on 17 March 2019. ChiCTR 1900021950).
Beyond the burn: Studies on the physiological effects of flamethrowers during World War II
Authors: Van Wyck David W.
Published: February 2020

Flamethrowers are widely considered one of warfare’s most controversial weapons and are capable of inflicting gruesome physical injuries and intense psychological trauma. Despite being the last of the major combatants in World War II (WWII) to develop them, the United States military quickly became the most frequent and adept operator of portable flamethrowers. This gave the U.S. military ample opportunity to observe the effects of flamethrowers on enemy soldiers. However, while most people in modern times would consider immolation by flamethrower to be an unnecessarily painful and inhumane way to inflict casualties, immolation was, at one point during World War II (WWII), referred to as “mercy killing” by the U.S. Chemical Warfare Service (CWS). This mischaracterization arose from a series of first-hand accounts describing what were believed to be quick, painless, and unmarred deaths, as well as from a poor and incomplete understanding of flamethrower lethality. As a result, indirect mechanisms such as hypoxia and carbon monoxide poisoning were generally absent from accounts of the flamethrower’s fatal effects. It was not until several years after flamethrowers were introduced to the frontlines that the CWS and National Defense Research Committee (NDRC) conducted a series of tests to better understand the physiological and toxicological effects of flamethrowers. This article examines how the initial absence of scientific data on the physiologic effects of flamethrowers led to an inaccurate understanding of their lethality, and bizarre claims that one of history’s most horrific instruments of war was considered one of the more “humane” weapons on the battlefield.
Eye gaze and facial displays of emotion during emotional film clips in remitted patients with bipolar disorder
Authors: Kjærstad Hanne Lie , Jørgensen Caroline Kamp , Broch-Due Ingrid , Kessing Lars Vedel , Miskowiak Kamilla
Published: February 2020

Background.

Aberrant emotional reactivity is a putative endophenotype for bipolar disorder (BD), but the findings of behavioral studies are often negative due to suboptimal sensitivity of the employed paradigms. This study aimed to investigate whether visual gaze patterns and facial displays of emotion during emotional film clips can reveal subtle behavioral abnormalities in remitted BD patients.

Methods.

Thirty-eight BD patients in full or partial remission and 40 healthy controls viewed 7 emotional film clips. These included happy, sad, and neutral scenarios and scenarios involving winning, risk-taking, and thrill-seeking behavior of relevance to the BD phenotype. Eye gaze and facial expressions were recorded during the film clips, and participants rated their emotional reactions after each clip.

Results.

BD patients showed a negative bias in both facial displays of emotion and self-rated emotional responses. Specifically, patients exhibited more fearful facial expressions during all film clips. This was accompanied by less positive self-rated emotions during the winning and happy film clips, and more negative emotions during the risk-taking/thrill-related film clips.

Conclusions.

These findings suggest that BD is associated with trait-related abnormalities in subtle behavioral displays of emotion processing. Future studies comparing patients with BD and unipolar depression are warranted to clarify whether these differences are specific to BD. If so, assessments of visual gaze and facial displays of emotion during emotional film clips may have the potential to be implemented in clinical assessments to aid diagnostic accuracy.
Intraspecific variation in sensitivity to food availability and temperature-induced phenotypic plasticity in the rotiferKeratella cochlearis
Authors: Ramos-Rodríguez Eloísa , Moreno Emilio , Conde-Porcuna José María
Published: February 2020

Organisms with wide environmentally-induced morphological plasticity and cosmopolitan distribution, e.g., the common freshwater rotifer Keratella cochlearis, are ideal models to study the evolution of plastic polymorphisms and the capacity of zooplankton to adapt to local selection conditions. We investigated population-level differences (population-by-environment interaction) in sensitivity to food availability and temperature-induced phenotypic plasticity between two clones of K. cochlearis (Gosse) isolated from neighboring populations in Ruidera Natural Park (Spain) with different trophic statuses: Tinaja (TIN) lake (mesotrophic) and Cueva Morenilla (MOR) lake (eutrophic). Using common-garden experiments, each clone proved to have a different sensitivity to food availability, with substantial phenotypic differences between them. When rotifers grew at moderate temperature (15.6°C), low food levels were more efficiently used by the TIN versus MOR clone, whereas high food levels were more efficiently used by the MOR versus TIN clone. The posterior spine was much longer and the lorica wider in the TIN versus MOR clone, with no difference in lorica length. Phylogenetic analysis based on COI sequences showed that both populations have the same haplotype. This is the first study to show possible local adaptation by a rotifer species to habitats that consistently differ in food availability. We also detected an intriguing deviation from the expected negative relationship between posterior spine length and temperature. Our experimental results indicate that intermediate temperatures may activate the gene responsible for spine elongation in K. cochlearis. This suggests that rotifers in nature could use water temperature as proxy signal of a change in predation risk before defense is needed.
MMR Deficiency is Homogeneous in Pancreatic Carcinoma and Associated with High Density of Cd8-Positive Lymphocytes
Authors: Fraune Christoph , Burandt Eike , Simon Ronald , Hube-Magg Claudia , Makrypidi-Fraune Georgia , Kluth Martina , Büscheck Franziska , Höflmayer Doris , Blessin Niclas Ch. , Mandelkow Tim , Li Wenchao , Perez Daniel , Izbicki Jakob R. , Wilczak Waldemar , Sauter Guido , Schrader Jörg , Neipp Michael , Mofid Hamid , Daniels Thies , Isbert Christoph , Clauditz Till S. , Steurer Stefan
Published: February 2020

Background

Microsatellite instability (MSI) has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of predicitive biomarkers. MSI has been reported in pancreatic cancer, but data on the possible extent of intratumoral heterogeneity are lacking.

Methods

To study MSI heterogeneity in pancreatic cancer, a tissue microarray (TMA) comprising 597 tumors was screened by immunohistochemistry with antibodies for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6.

Results

In six suspicious cases, large section immunohistochemistry and microsatellite analysis (Bethesda panel) resulted in the identification of 4 (0.8%) validated MSI cases out of 480 interpretable pancreatic ductal adenocarcinomas. MSI was absent in 55 adenocarcinomas of the ampulla of Vater and 7 acinar cell carcinomas. MMR deficiency always involved MSH6 loss, in three cases with additional loss of MSH2 expression. Three cancers were MSI-high and one case with isolated MSH6 loss was MSS in PCR analysis. The analysis of 44 cancer-containing tumor blocks revealed that the loss of MMR protein expression was always homogeneous in affected tumors. Automated digital image analysis of CD8 immunostaining demonstrated markedly higher CD8 + tumor infiltrating lymphocytes in tumors with (mean = 685, median = 626) than without (mean = 227; median = 124) MMR deficiency (p < 0.0001), suggesting a role of MSI for immune response.

Conclusions

Our data suggest that MSI occurs early in a small subset of ductal adenocarcinomas of the pancreas and that immunohistochemical MMR analysis on limited biopsy or cytology material may be sufficient to estimate MMR status of the entire cancer mass.
Influence of Additives on Zinc Oxide-Based Dye Sensitized Solar Cells
Authors: Geleta Tesfaye Abebe , Imae Toyoko
Published: February 2020

In order to enhance the power conversation efficiency of dye sensitized solar cells (DSSCs), various trials have been reported. In this work, composites of n-type semiconductors, ZnO and ZrS2 were fabricated in DSSCs. In addition, the effect of addition of carbon dots on them was assessed. When 10 wt% of ZrS2 was mixed with ZnO, the power conversion efficiency achieved 1.6 times of that of ZnO but the coexistence of carbon dots and ZrS2 in ZnO DSSC resulted the decrease of the power conversion efficiency. ZrS2 forms an n-n heterojunction with ZnO and contributes to the fast transfer of electrons to the conductive electrode substrate. Meanwhile, when carbon dots are added to ZnO/ZrS2(10 wt%) DSSC, the electrons generated and transferred to ZrS2 should recombine with holes generated and transferred to photosensitizer. These situations are compared with a composite system of ZnO/carbon dots previously reported and suggest us the selection of preferable combinations of composite DSSCs.
Do Immigrants Assimilate More Slowly Today than in the Past?
Authors: Abramitzky Ran , Boustan Leah , Eriksson Katherine
Published: February 2020

Using millions of historical census records and modern birth certificates, we document that immigrants assimilated into US society at similar rates in the past and present. We measure cultural assimilation as immigrants giving their children less foreign names after spending more time in the United States, and show that immigrants erase about one‑half of the naming gap with natives after 20 years both historically and today. Immigrants from poorer coun‑ tries choose more foreign names upon first arrival in both periods but are among the fastest to shift toward native‑sounding names. We find substantial cultural assimilation for immigrants of all education levels. (JEL J15, N31, N32, Z13)
Magnetic resonance imaging assessment of chemotherapy-related adipocytic maturation in myxoid/round cell liposarcomas: specificity and prognostic value
Authors: Crombe Amandine , Sitbon Maxime , Stoeckle Eberhard , Italiano Antoine , Buy Xavier , Le Loarer François , Kind Michèle
Published: February 2020

Objective:

To investigate the specificity, clinical implication and prognostic value of MRI adipocytic maturation (MAM) in myxoid/round cells liposarcomas (MRC-LPS) treated with neoadjuvant chemotherapy (NAC).

Methods:

Of the 89 patients diagnosed with MRC-LPS at our sarcoma reference center between 2008 and 2018, 28 were included as they were treated with NAC, surgery and radiotherapy. All patients underwent contrast-enhanced MRIs at baseline and late evaluation. A control cohort of 13 high-grade pleomorphic and dedifferentiated LPS with same inclusion criteria was used to evaluate the specificity of MAM in MRC-LPS. Two radiologists analyzed the occurrence of MAM, changes in the tumor architecture, shape and surrounding tissues during NAC. Pathological features of tumor samples were reviewed and correlated with MRI. Metastatic relapse-free survival was estimated with Kaplan–Meier curves and Cox models. Associations between prognostic T1-based delta-radiomics features and MAM were investigated with Student t-test.

Results:

MAM was more frequent in MRC-LPS (p = 0.045) and not specific of any type of chemotherapy (p = 0.7). Regarding MRC-LPS, 14 out of 28 patients (50%) demonstrated MAM. Eight patients showed metastatic relapses. MAM was not associated with metastatic relapse-free survival (p = 0.9). MAM correlated strongly with the percentage of histological adipocytic differentiation on surgical specimen (p < 0.001), which still expressed the tumor marker NY-ESO-1. None of the prognostic T1-based delta-radiomics features was associated with MAM.

Conclusion:

MAM seems a neutral event during NAC.

Advances in knowledge:

MAM predominated in MRC-LPS and was not specific of a type of chemotherapy. Occurrence of MAM was not associated with better patients’ metastasis free survival.
One end to rule them all: Non-homologous end-joining and homologous recombination at DNA double-strand breaks
Authors: Ensminger Michael , Löbrich Markus
Published: February 2020

Double-strand breaks (DSBs) represent the most severe type of DNA damage since they can lead to genomic rearrangements, events that can initiate and promote tumorigenic processes. DSBs arise from various exogenous agents that induce two single-strand breaks at opposite locations in the DNA double helix. Such two-ended DSBs are repaired in mammalian cells by one of two conceptually different processes, non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ has the potential to form rearrangements while HR is believed to be error-free since it uses a homologous template for repair. DSBs can also arise from single-stranded DNA lesions if they lead to replication fork collapse. Such DSBs, however, have only one end and are repaired by HR and not by NHEJ. In fact, the majority of spontaneously arising DSBs are one-ended and HR has likely evolved to repair one-ended DSBs. HR of such DSBs demands the engagement of a second break end that is generated by an approaching replication fork. This HR process can cause rearrangements if a homologous template other than the sister chromatid is used. Thus, both NHEJ and HR have the potential to form rearrangements and the proper choice between them is governed by various factors, including cell cycle phase and genomic location of the lesion. We propose that the specific requirements for repairing one-ended DSBs have shaped HR in a way which makes NHEJ the better choice for the repair of some but not all two-ended DSBs.
Visualizing the structure and motion of the long noncoding RNA HOTAIR
Authors: Spokoini-Stern Rachel , Stamov Dimitar , Jessel Hadass , Aharoni Lior , Haschke Heiko , Giron Jonathan , Unger Ron , Segal Eran , Abu-Horowitz Almogit , Bachelet Ido
Published: February 2020

Long noncoding RNA molecules (lncRNAs) are estimated to account for the majority of eukaryotic genomic transcripts, and have been associated with multiple diseases in humans. However, our understanding of their structure–function relationships is scarce, with structural evidence coming mostly from indirect biochemical approaches or computational predictions. Here we describe direct visualization of the lncRNA HOTAIR (HOx Transcript AntIsense RNA) using atomic force microscopy (AFM) in nucleus-like conditions at 37°. Our observations reveal that HOTAIR has a discernible, although flexible, shape. Fast AFM scanning enabled the quantification of the motion of HOTAIR, and provided visual evidence of physical interactions with genomic DNA segments. Our report provides a biologically plausible description of the anatomy and intrinsic properties of HOTAIR, and presents a framework for studying the structural biology of lncRNAs.
Treatment effectiveness of neonatal sepsis formed in the conditions of adverse ecological environment
Authors: Vlasova Olena Vasylivna , Hrytsiuk Mariana Ivanivna
Published: February 2020

The analysis of the effectiveness of treatment of patients in the newborn comparison groups allowed to confirm that, taking into account the relative risk reduction of its manifestations, in the children of the main group, it was less successful in the first clinical group, although the mortality due to sepsis in these patients was not significantly higher (7,8 ± 2.2% in group I and 6.7 ± 2.2% in group II, P> 0.05)
Decreased level of consciousness in a child: recognition and management
Authors: Patel Neal , Nandakumar Naveen , Heaton Paul Anthony , Le Huray Vicki , Paul Siba Prosad
Published: February 2020

A child presenting with decreased level of conscious (dLOC) is of great concern due to the wide range of possible causes, and potential for death or serious long-term sequelae. It is therefore vital that health professionals can recognise a child with dLOC quickly, intervene appropriately and escalate for senior review as a matter of urgency. This article provides an explanation for the mechanisms of decreased consciousness, outlines the different causative pathologies, and provides a simple and logical approach to the first-line recognition and management that a health professional may apply when faced with such a patient. Illustrative case studies have been included, to demonstrate how children with dLOC may present in clinical practice