bluuebunny/crossref_metadata_2025 huggingface dataset:
The uses of fig (Ficus) by five ethnic minority communities in Southern Shan State, Myanmar
Authors: Mon Aye Mya , Shi Yinxian , Yang Xuefei , Hein Pyae Phyo , Oo Thaung Naing , Whitney Cory W. , Yang Yongping
Published: September 2020

Background

Most regions of Myanmar fall within the Indo-Burma Biodiversity Hotspot and are threatened with biodiversity loss. Development of a comprehensive framework for sustainable development is crucial. Figs are ecological keystone species within these regions and are also important for traditional spiritual food and health uses, which often have accompanying conservation practices. The traditional use and management of figs may offer clues to help guide the development of national policies for sustainable development. In this study, we showcase the rich ethnobotanical knowledge as well as the variety of collection and conservation practices of figs among five ethnic groups in Southern Shan State.

Methods

We performed both key informant and semi-structured interviews with 114 informants from five ethnic groups. Their uses for figs were categorized according to local practices and recipes. Informants were asked about trends in conservation status over the past 10 years and any conservation-related customs and practices. Data were analyzed quantitatively with common quantitative ethnobotany indices, the use report (UR) and use value (UV).

Results

Informants reported the uses of eight fig species (Ficus auricularta,F. concinna,F. geniculata,F. hispida,F. racemosa,F. religiosa,F. semicordata, andF. virens).F. geniculataandF. virenswere most useful (UR = 228) and were used by all five ethnic groups, corresponding to a high use value (UV = 2). Treatments for 16 diseases were reported from seven species. Household consumption, economic and sacred uses were accompanied by sustainable practices of harvest and protection. Traditional taboos,in situandex situconservation were common especially for highly demanded species (F. geniculataandF. virens) and the sacred figF. religiosa.

Conclusion

Findings suggest that figs are useful for food (all informants) and medicine (13.16% of the informants) in the study area. Traditional taboos,in situandex situconservation practices help to maintain sustainable utilization of locally important figs. This is an early contribution to the traditional knowledge of edible figs. Although similar uses have been reported in neighboring countries for seven of the fig species, the ethnobotanical use ofF. concinnais novel.
A propensity score-matched analysis between patients with high hip dislocation after childhood pyogenic infection and Crowe IV developmental dysplasia of the hip in total hip arthroplasty with subtrochanteric shortening osteotomy
Authors: Zhao Enze , Liu Zunhan , Ding Zichuan , Luo Zhenyu , Li Hao , Zhou Zongke
Published: September 2020

Background

Whether satisfactory clinical and radiological outcomes of total hip arthroplasty (THA) with subtrochanteric shortening osteotomy (SSO) in high hip dislocation after childhood pyogenic infection can be achieved as in Crowe IV developmental dysplasia of the hip (DDH) remains unclear.

Methods

Between September 2009 and December 2016, 151 primary THAs performed at our institution using similar SSO technique and prosthetic design were retrospectively reviewed. After excluding patients who met exclusion criteria, 29 patients were identified as high dislocation (Crowe IV) after childhood infection (HDACI) and 107 as Crowe IV developmental dysplasia of the hip (DDH). Propensity score matching was used to select 29 Crowe IV DDH patients as a control group for the HDACI group with comparable preoperative conditions. Clinical and radiological outcomes and complication were compared and analyzed. The mean follow-up duration of the 2 groups was 5.0 years.

Results

The mean Harris hip score (HHS) and the mean score in range of motion (ROM) domain of the modified Merle d’Aubigné-Postel (MAP) were 84.6 and 4.5 in the HDACI group, compared with 88.3 and 4.9 in the DDH group; there was significant difference between the 2 groups in these parameters (P= 0.015 and 0.035, respectively). Meanwhile, in the HDACI group, the median time of osteotomy union was 4 months and osteotomy nonunion rate was 3%; no significant difference was detected in the median time of osteotomy union and osteotomy nonunion rate between the 2 groups (P= 0.388 and 1.000, respectively). And no significant difference was found in the rate of complications between two groups.

Conclusions

HDACI patients who received THA combined with SSO could achieve similar satisfactory results as DDH patients in Crowe type IV. The fixation technique of autogenous cortical bone struts had a positive influence on osteotomy healing of SSO in this specific setting.
Development of a patient-reported outcome questionnaire for aplastic anemia and paroxysmal nocturnal hemoglobinuria (PRO-AA/PNH)
Authors: Weisshaar Kimmo , Ewald Hannah , Halter Jörg , Gerull Sabine , Schönfeld Sandra , Senft Yuliya , Martinez Maria , Leuppi-Taegtmeyer Anne , Khanna Nina , Maier Birgit , Risitano Antonio , Peffault de Latour Regis , Tichelli Andre , Passweg Jakob , Drexler Beatrice
Published: September 2020

Background

The introduction of new therapy modalities has significantly improved the outcome of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) patients. However, relatively little is known about the exact disease burden of AA/PNH since standardized assessments of symptoms including health-related quality of life (HRQoL) are frequently missing or inadequately designed for this rare patient group. We aimed to develop AA/PNH-specific questionnaires for self-reporting of symptoms, which could be included in electronic platforms for data collection and patient care.

Methods

By scoping review, we extracted any reported symptoms in AA/PNH and their prevalence from the literature (Phase I). Consensus rounds with patients and medical experts were conducted to identify core symptoms reported in the literature and to add missing items (Phase II). Ultimately, AA/PNH-specific patient-reported outcome (PRO) questionnaires including the selected measures were designed (Phase III).

Results

AA symptoms from 62 and PNH symptoms from 45 observational studies were extracted from the literature. Twenty-four patients and seven medical experts identified 11 core symptoms including HRQoL issues after three consensus rounds. Significant differences in the symptom ranking of patients versus medical experts could be observed. Therefore, patient- as well as expert-centered PRO questionnaires in AA and PNH were created following the concepts of validated instruments.

Conclusion

The development of symptom self-reporting questionnaires for AA and PNH was feasible and the disease-specific PRO questionnaires can now be validated within a web-based workflow in a subsequent feasibility study.
Exposure to benzylpenicillin after different dosage regimens in growing pigs
Authors: Sjölund Marie , Ekstrand Carl , Wallgren Per , Bondesson Ulf , Pringle Märit , Bengtsson Björn
Published: September 2020

Background

Penicillin is important for treatment of pigs, but data on its absorption and disposition in pigs are sparse. This is reflected by the variation in recommended dosages in the literature. Inadequate dosage may lead to treatment failure and selection of resistant bacteria. To optimize treatment regimens, plasma exposure to benzylpenicillin for two sustained release formulations of procaine benzylpenicillin for intramuscular administration was studied in growing pigs by means of tandem mass spectrometry (UPLC–MS/MS). One formulation was an aqueous suspension, Ethacilin® vet (ETH), and the other an oily suspension, Ultrapen vet (UPA). Benzylpenicillin exposure after intravenous administration of potassium benzylpenicillin was also explored. Exposure profiles were first studied after single administrations of the approved dosages in healthy pigs and then after repeated administration of different dosages in pigs inoculated intranasally with an Actinobacillus pleuropneumoniae serotype 2 strain.

Results

After intravenous administration of benzylpenicillin (n = 6), maximum plasma concentration (Cmax), 1860–9318 µg/L, was observed after 15 min. At four h, plasma concentrations decreased to 15–76 µg/L. After intramuscular administration of ETH (n = 6) Cmax, 1000–4270 µg/L, was observed within one h (tmax) in 5 pigs but at four h in one pig. Cmax for UPA (n = 6), 910–3220 µg/L, was observed within one h in three pigs, but at four or 24 h in three pigs. For both ETH and UPA, the terminal phase was characterized by slow decline compared with intravenous administration. Repeated administration of different dosages of ETH and UPA in pigs inoculated with A. pleuropneumoniae (n = 54) showed that the approved dose for UPA (30 mg/kg, qd) but not for ETH (20 mg/kg, qd) gave adequate plasma exposure for bacteria with a penicillin MIC of 500 µg/L. However, more frequent dosing of ETH (bid) or increased dosage gave an adequate exposure.

Conclusions

The approved dosage of ETH provided insufficient plasma exposure for adequate therapy of infections caused by A. pleuropneumoniae or other bacteria with a penicillin MIC of 500 µg/L. More frequent ETH dosing (bid) or an increased dosage would improve exposure. The approved dosage of UPA however provided adequate exposure.
Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis
Authors: Papareddy Ranjith K. , Páldi Katalin , Paulraj Subramanian , Kao Ping , Lutzmayer Stefan , Nodine Michael D.
Published: September 2020

Background

Eukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development and must be properly re-established after its decondensation. Small interfering RNAs (siRNAs) promote heterochromatin formation, but little is known about how chromatin regulates siRNA expression.

Results

We demonstrate that thousands of transposable elements (TEs) produce exceptionally high levels of siRNAs inArabidopsis thalianaembryos. TEs generate siRNAs throughout embryogenesis according to two distinct patterns depending on whether they are located in euchromatic or heterochromatic regions of the genome. siRNA precursors are transcribed in embryos, and siRNAs are required to direct the re-establishment of DNA methylation on TEs from which they are derived in the new generation. Decondensed chromatin also permits the production of 24-nt siRNAs from heterochromatic TEs during post-embryogenesis, and siRNA production from bipartite-classified TEs is controlled by their chromatin states.

Conclusions

Decondensation of heterochromatin in response to developmental, and perhaps environmental, cues promotes the transcription and function of siRNAs in plants. Our results indicate that chromatin-mediated siRNA transcription provides a cell-autonomous homeostatic control mechanism to help reconstitute pre-existing chromatin states during growth and development including those that ensure silencing of TEs in the future germ line.
Does immediate smart feedback on therapy adherence and inhalation technique improve asthma control in children with uncontrolled asthma? A study protocol of the IMAGINE I study
Authors: Sportel Esther T. , Oude Wolcherink Martijn J. , van der Palen Job , Lenferink Anke , Thio Boony J. , Movig Kris L. L. , Brusse-Keizer Marjolein G. J.
Published: September 2020

Background

Many asthmatic children suffer from uncontrolled asthma with frequent exacerbations, despite an optimal treatment plan using inhalation medication. Studies have shown that therapy adherence and inhalation technique are often suboptimal in asthmatic children, but these have traditionally been hard to measure. A novel device functioning as an add-on to the inhaler has been developed to measure both aspects by recording vibration patterns during inhalation. This data can be converted to smart feedback and provided to patients immediately via a mobile application. The aim of this study is to improve asthma control in children between 6 and 18 years old by providing immediate smart feedback on the intake of inhalation medication. Asthma control will be measured by forced expiratory volume in 1 s, (Childhood) Asthma Control Test ((c-)ACT) score, and lung function variability and reversibility.

Methods

The study will be performed in Medisch Spectrum Twente (Enschede, The Netherlands). The goal is to include 68 uncontrolled moderate to severe asthmatic children between 6 and 18 years old who receive controller inhalation medication through the Nexthaler®, Ellipta®, or Spiromax®. The study consists of three phases. Phase 1 is observational and will last 4 weeks to observe the baseline adherence and inhalation technique as monitored by the add-on device. A randomised controlled trial lasting 6 weeks will be performed in phase 2. Patients in the intervention group will receive immediate smart feedback about the performed inhalations via a mobile application. In the control group, adherence and inhalation technique will be monitored, but patients will not receive feedback. In phase 3, also lasting 6 weeks, the feedback will be ceased for all children and revision of current therapy may occur, depending on the findings in phase 2. Asthma control can be assessed by means of spirometry (both at home and in the hospital) and (c-)ACT questionnaires.

Discussion

Immediate smart feedback may improve therapy adherence and inhalation technique, and thus asthma control in children and prevent unnecessary switches to targeted biologics. Performing this study in children is desired, since they are known to react differently to feedback and medication than adults.

Trial registration

Dutch Trial Register NL7705. Registered on 29 April 2019
Tocilizumab in treatment-naïve patients with Takayasu arteritis: TOCITAKA French prospective multicenter open-labeled trial
Authors: Mekinian Arsene , Saadoun David , Vicaut Eric , Thietart Sara , Lioger Bertrand , Jego Patrick , Bleibtreu Alexandre , Limal Nicolas , Connault Jerome , Gottenberg Jacques-Eric , Lhorte Pauline , Bertola Jean Pierre , Delforge Juliette , Ferreira-Maldent Nicole , Perlat Antoinette , Talib Zohra , Vautier Matthieu , Savey Léa , Quiere Isabelle , Cacoub Patrice , Fain Olivier ,   for the French Takayasu network
Published: September 2020

Objectives

To assess long-term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK).

Methods

Prospective open-labeled trial in naïve patients with TAK who received steroids at the dose of 0.7 mg/kg/day and 7 infusions of 8 mg/kg/month of tocilizumab. The primary endpoint was the number of patients who discontinued steroids after 7 infusions of tocilizumab. Secondary endpoints included disease activity and the number of relapses during 18-month follow-up.

Results

Thirteen patients with TAK were included, with a median age of 32 years [19–45] and 12 (92%) females. Six (54%) patients met the primary end-point. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3, 4] at baseline, versus 1 [0–2] after 6 months;p < 0.001), ITAS-2010 score (5 [2–7] versus 3 [0–8];p = 0.002), and ITAS-A score (7 [4–10] versus 4 [1–15];p = 0.0001)]. During the 12-month follow-up after tocilizumab discontinuation, a relapse occurred among 5 patients (45%) out of 11 in which achieved remission after 6 months of tocilizumab.

Conclusion

Tocilizumab seems an effective steroid sparing therapy in TAK, but maintenance therapy is necessary.

Trial registration

ClinicalTrials.govNCT02101333. Registered on 02 April 2014.
Laparoscopic sleeve gastrectomy in obese patients with ventricular assist devices: a data note
Authors: daSilva-deAbreu Adrian , Garikapati Kiran , Alhafez Bader Aldeen , Desai Sapna , Eiswirth Clement , Krim Selim , Patel Hamang , Lavie Carl J. , Ventura Hector O. , Loro-Ferrer Juan Francisco , Mandras Stacy A.
Published: September 2020

Objectives

Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight after implantation, which is associated with higher complication rates and is a contraindication for heart transplantation (HT). The objective was to analyze the outcomes of obese patients with ESHF and VADs who underwent laparoscopic sleeve gastrectomy (LSG) at Ochsner Medical Center in New Orleans, which is the only program performing VADs and HT in the State of Louisiana, and also one of the largest VAD centers in the USA.

Data description

This dataset contains detailed baseline, perioperative, and long-term data of patients with VADs undergoing LSG. These variables were collected retrospectively from electronic medical records. Patients who achieved ≥ 50% excess BMI loss, BMI ≤ 35 kg/m2, listing for HT, HT, or myocardial recovery were identified and the timing to each of these milestones was documented. These data can be used alone or in combination with other datasets to achieve a larger sample size with more power for further analysis of these variables, which include the most important, standard, and objective bariatric and ESHF outcomes of patients with VADs undergoing LSG. Elaboration of composite outcomes is feasible.
FOXQ1 promotes the osteogenic differentiation of bone mesenchymal stem cells via Wnt/β-catenin signaling by binding with ANXA2
Authors: Xiang Lusai , Zheng Junming , Zhang Mengdan , Ai Tingting , Cai Bin
Published: September 2020

Background

This study investigated the role of Forkhead box Q1 (FOXQ1) in the osteogenic differentiation of bone mesenchymal stem cells.

Methods

Mouse bone mesenchymal stem cells (mBMSCs) were transfected with lentivirus to generate Foxq1-overexpressing mBMSCs, Foxq1-suppressed mBMSCs, and mBMSC controls. The activity of osteogenic differentiation was evaluated with alizarin red staining, alkaline phosphatase activity assay, and RT-qPCR. Wnt/β-catenin signaling activities were compared among groups by TOPFlash/FOPFlash assay, immunofluorescence staining, and western blot assay of beta-catenin (CTNNB1). Coimmunoprecipitation mass spectrometry was also carried out to identify proteins binding with FOXQ1.

Results

Our data showed that FOXQ1 expression was positively correlated with the osteogenic differentiation of the mBMSCs. FOXQ1 also promoted the nuclear translocation of CTNNB1 in the mBMSCs, enhancing Wnt/β-catenin signaling, which was also shown to be essential for the osteogenic differentiation-promoting effect of FOXQ1 in the mBMSCs. Annexin A2 (ANXA2) was bound with FOXQ1, and its depletion reversed the promoting effect of FOXQ1 on Wnt/β-catenin signaling.

Conclusion

These results showed that FOXQ1 binds with ANXA2, promoting Wnt/β-catenin signaling in bone mesenchymal stem cells, which subsequently promotes osteogenic differentiation.
Molecular representations in AI-driven drug discovery: a review and practical guide
Authors: David Laurianne , Thakkar Amol , Mercado Rocío , Engkvist Ola
Published: September 2020

The technological advances of the past century, marked by the computer revolution and the advent of high-throughput screening technologies in drug discovery, opened the path to the computational analysis and visualization of bioactive molecules. For this purpose, it became necessary to represent molecules in a syntax that would be readable by computers and understandable by scientists of various fields. A large number of chemical representations have been developed over the years, their numerosity being due to the fast development of computers and the complexity of producing a representation that encompasses all structural and chemical characteristics. We present here some of the most popular electronic molecular and macromolecular representations used in drug discovery, many of which are based on graph representations. Furthermore, we describe applications of these representations in AI-driven drug discovery. Our aim is to provide a brief guide on structural representations that are essential to the practice of AI in drug discovery. This review serves as a guide for researchers who have little experience with the handling of chemical representations and plan to work on applications at the interface of these fields.
Effects of health insurance on patient demand for physician services
Authors: Dugan Jerome
Published: September 2020

Background

In recent years, policymakers have sought to reduce health disparities between the insured and uninsured through a federal health insurance expansion policy; however, disparities continue to persist among the insured population. One potential explanation is that the use of healthcare services varies by the type of health insurance coverage due to differences in the design of coverage. The aim of this study is to examine whether health insurance coverage type is associated with the structure and use of healthcare services.

Methods

The nationally representative Medical Expenditure Panel Survey and multinomial logistic regression are used to estimate the effects of different types of health coverage on the combinations of routine and emergency care sought and received.

Results

The multinomial logistic regression analysis for the overall sample revealed privately insured respondents reported higher use of routine care only p < 0.01 and lower use of emergency room care only (− 2.13%; p < 0.01) than the uninsured. The publicly insured reported similar trends for use of routine care only (17.93%; p < 0.01) as the privately insured, as compared to the uninsured. Both the privately and publicly insured reported higher use of a mixture of care; however, publicly insured were more likely to use a mixture of care (8.57%, p < 0.01).

Conclusion

The results show that health insurance is associated with higher use of the physician services, but does not promote the use of cost-effective schedules of care among the publicly insured.
On high-order compact schemes for the multidimensional time-fractional Schrödinger equation
Authors: Eskar Rena , Feng Xinlong , Kasim Ehmet
Published: September 2020

In this article, some high-order compact finite difference schemes are presented and analyzed to numerically solve one- and two-dimensional time fractional Schrödinger equations. The time Caputo fractional derivative is evaluated by the L1 and L1-2 approximation. The space discretization is based on the fourth-order compact finite difference method. For the one-dimensional problem, the rates of the presented schemes are of order $O(\tau ^{2-\alpha }+h^{4})$
O
(

τ

2
−
α

+

h
4

)
and $O(\tau ^{3-\alpha }+h^{4})$
O
(

τ

3
−
α

+

h
4

)
, respectively, with the temporal step size τ and the spatial step size h, and $\alpha \in (0,1)$
α
∈
(
0
,
1
)
. For the two-dimensional problem, the high-order compact alternating direction implicit method is used. Moreover, unconditional stability of the proposed schemes is discussed by using the Fourier analysis method. Numerical tests are performed to support the theoretical results, and these show the accuracy and efficiency of the proposed schemes.
A radiomics-based model on non-contrast CT for predicting cirrhosis: make the most of image data
Authors: Wang Jin-Cheng , Fu Rao , Tao Xue-Wen , Mao Ying-Fan , Wang Fei , Zhang Ze-Chuan , Yu Wei-Wei , Chen Jun , He Jian , Sun Bei-Cheng
Published: September 2020

Background

To establish and validate a radiomics-based model for predicting liver cirrhosis in patients with hepatitis B virus (HBV) by using non-contrast computed tomography (CT).

Methods

This retrospective study developed a radiomics-based model in a training cohort of 144 HBV-infected patients. Radiomic features were extracted from abdominal non-contrast CT scans. Features selection was performed with the least absolute shrinkage and operator (LASSO) method based on highly reproducible features. Support vector machine (SVM) was adopted to build a radiomics signature. Multivariate logistic regression analysis was used to establish a radiomics-based nomogram that integrated radiomics signature and other independent clinical predictors. Performance of models was evaluated through discrimination ability, calibration and clinical benefits. An internal validation was conducted in 150 consecutive patients.

Results

The radiomics signature comprised 25 cirrhosis-related features and showed significant differences between cirrhosis and non-cirrhosis cohorts (P < 0.001). A radiomics-based nomogram that integrates radiomics signature, alanine transaminase, aspartate aminotransferase, globulin and international normalized ratio showed great calibration and discrimination ability in the training cohort (area under the curve [AUC]: 0.915) and the validation cohort (AUC: 0.872). Decision curve analysis confirmed the most clinical benefits can be provided by the nomogram compared with other methods.

Conclusions

Our developed radiomics-based nomogram can successfully diagnose the status of cirrhosis in HBV-infected patients, that may help clinical decision-making.
Baicalin alleviates lipopolysaccharide-induced neuroglial activation and inflammatory factors activation in hippocampus of adult mice
Authors: Shah Murad-Ali , Park Dong-Ju , Kang Ju-Bin , Kim Myeong-Ok , Koh Phil-Ok
Published: September 2020

Baicalin is a natural flavonoid that exerts a variety of pharmaceutical effects such as anti-inflammatory and antioxidant. Lipopolysaccharide (LPS) is an endotoxin that releases inflammatory cytokines and induces inflammatory response. This study was investigated the anti-inflammatory mechanism of baicalin against LPS-induced inflammatory response in the hippocampus. Adult mice were randomly grouped into control, LPS-treated, and LPS and baicalin co-treated animals. LPS (250 μg/kg/day) and baicalin (10 mg/kg/day) were administered intraperitoneally for 7 consecutive days. We measured neuroglia cells activation and inflammatory factors activation using Western blot analysis and immunofluorescence staining techniques. Ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) are widely used as microglia and astrocyte markers, respectively. LPS treatment increased Iba-1 and GFAP expression, while baicalin co-treatment attenuated this overexpression. Nuclear factor-kappa B (NF-κB) is a key mediator of inflammation. Baicalin co-treatment alleviated LPS-induced increase of NF-κB in the hippocampus. In addition, LPS treatment upregulated pro-inflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). However, baicalin co-treatment prevented LPS-induced increases of IL-1β and TNF-α in the hippocampus. Results from the present study showed that baicalin suppresses LPS-induced neuroinflammation by regulating microglia and astrocyte activation and modulating inflammatory factors in the hippocampus. Thus, these results demonstrate that baicalin has neuroprotective effect by alleviates microglia and astrocyte activation and modulates inflammatory response by suppressing NF-κB expression in hippocampus with neuroinflammation caused by LPS.
Cryopreservation of mouse resources
Authors: Takeo Toru , Nakao Satohiro , Nakagawa Yoshiko , Sztein Jorge M. , Nakagata Naomi
Published: September 2020

The cryopreservation of sperm and embryos is useful to efficiently archive valuable resources of genetically engineered mice. Till date, more than 60,000 strains of genetically engineered mice have been archived in mouse banks worldwide. Researchers can request for the archived mouse strains for their research projects. The research infrastructure of mouse banks improves the availability of mouse resources, the productivity of research projects, and the reproducibility of animal experiments. Our research team manages the mouse bank at the Center for Animal Resources and Development in Kumamoto University and continuously develops new techniques in mouse reproductive technology to efficiently improve the system of mouse banking. In this review, we introduce the activities of mouse banks and the latest techniques used in mouse reproductive technology.
Prevalence of treatment resistance and clozapine use in early intervention services
Authors: Stokes Imogen , Griffiths Siân Lowri , Jones Rowena , Everard Linda , Jones Peter B. , Fowler David , Hodgekins Joanne , Amos Tim , Freemantle Nick , Sharma Vimal , Marshall Max , Singh Swaran P. , Birchwood Max , Upthegrove Rachel
Published: September 2020

Background

Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.

Aims

This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.

Method

Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.

Results

A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.

Conclusions

Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves’ Disease Patients by Propionic Acid
Authors: Su Xinhuan , Yin Xianlun , Liu Yue , Yan Xuefang , Zhang Shucui , Wang Xiaowei , Lin Zongwei , Zhou Xiaoming , Gao Jing , Wang Zhe , Zhang Qunye
Published: September 2020

Background

Graves’ disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive.

Objective

To investigate the association and mechanism between intestinal flora and GD.

Methods

We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation.

Results

The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy.

Conclusions

Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.
Predictors of Chronic LH-Testosterone Axis Suppression in Male Macroprolactinomas With Normoprolactinemia on Cabergoline
Authors: Sehemby Manjeetkaur , Lila Anurag Ranjan , Sarathi Vijaya , Shah Ravikumar , Sankhe Shilpa , Jaiswal Sanjeet Kumar , Ramteke-Jadhav Swati , Patil Virendra , Shah Nalini , Bandgar Tushar
Published: September 2020

Context

Data are limited regarding prevalence, predictors, and mechanisms of persistent hypogonadotropic hypogonadism (HH) in males with a macroprolactinoma who achieve normoprolactinemia on dopamine-agonist therapy. None of the previous studies provide cutoffs to predict the achievement of eugonadism.

Objective

The objective of this work is to evaluate the prevalence of persistent HH and its determinants in men with a macroprolactinoma who achieve normoprolactinemia on cabergoline monotherapy.

Design and Setting

This retrospective study with prospective cross-sectional evaluation took place at a tertiary health care center.

Patients

Study participants included men with a macroprolactinoma and baseline HH who achieved normoprolactinemia on cabergoline monotherapy.

Main Outcome Measures

Outcome measures of this study included the prevalence of persistent HH and its predictors.

Results

Thirty participants (age, 38.3 ± 10.1 years) with baseline tumor size of 4.08 ± 1.48 cm and median (interquartile range) prolactin of 2871 ng/mL (range, 1665-8425 ng/mL) were included. Eight of 30 participants achieved eugonadism after a median follow-up of 3 years. Patients with persistent HH had suppression of the luteinizing hormone (LH)-testosterone axis with sparing of other anterior pituitary hormonal axes, including follicle-stimulating hormone-inhibin B. Baseline prolactin (1674 vs 4120 ng/mL; P = .008) and maximal tumor diameter (2.55 ± 0.36 vs 4.64 ± 1.32 cm; P = .003) were lower in patients who achieved eugonadism. Baseline maximal tumor diameter less than or equal to 3.2 cm (sensitivity: 75%, specificity: 63.6%) and serum prolactin less than or equal to 2098 ng/mL (sensitivity: 87.5%, specificity: 77.3%) best predicted reversal of HH.

Conclusion

Recovery of the LH-testosterone axis occurred in 26.7% of men with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Higher baseline tumor size and serum prolactin predict persistent HH. Our data favor chronic functional modification of the hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.
Association of the Obesity Paradox With Objective Physical Activity in Patients at High Risk of Sudden Cardiac Death
Authors: Li Xiaoyao , Chen Keping , Hua Wei , Su Yangang , Yang Jiefu , Liang Zhaoguang , Xu Wei , Xue Xiaodi , Zhang Shu , Zhao Shuang
Published: September 2020

Objective

To investigate the obesity paradox and its interrelationship with objective physical activity (PA) in patients at high risk of sudden cardiac death.

Methods

A total of 782 patients with implantable cardioverter-defibrillators/cardiac resynchronization therapy defibrillators in the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-Implantable Patients registry were retrospectively analyzed and grouped by body mass index (BMI) (kg/m2): normal weight (18.5 ≤ BMI < 25) and overweight or class I obesity (25 ≤ BMI < 35). PA was measured with home monitoring and categorized into 4 groups (Q1-Q4) by the baseline quartiles. The main endpoint was all-cause mortality.

Results

During a mean follow-up period of 59.9 ± 21.9 months, 182 all-cause mortality events occurred. Mortality tended to be lower in overweight and obesity patients (18.9% vs 25.1%, P = 0.061) and decreased by PA quartiles (44.1% vs 22.6% vs 15.3% vs 11.2%, Q1-Q4, P < 0.001). Multivariate Cox analysis indicated BMI (hazard ratio, 0.918; 95% confidence interval, 0.866-0.974; P = 0.004) and PA (0.436, 0.301-0.631, Q2 vs Q1; 0.280, 0.181-0.431, Q3 vs Q1; 0.257, 0.158-0.419, Q4 vs Q1; P < 0.001 for all) were associated with reduced risk. The obesity paradox was significant in the total cohort (log rank P = 0.049) and low PA group (log rank P = 0.010), but disappeared in the high PA group (log rank P = 0.692). Dose-response curves showed a significant reduction in risk with low-moderate PA, and the pattern varied between different BMI groups.

Conclusions

The obesity paradox only persisted in physically inactive patients. PA might be related to the development of the obesity paradox.
Editors’ Introduction
Authors: Bray Mark , Namakkal Jessica , Riccò Giulia , Roubinek Eric
Published: September 2020

By taking as a point of departure post-1945 self-proclaimed anti-fascist movements, whose claim to combat fascism has often been discarded as politically irrelevant or bombastic, this introduction invites readers to speculate on the rhetorical value implied in the word fascism. Although the term carries within it an almost abysmal capacity for political oversimplification, we argue that it also possesses an undeniable rhetorical value whose function as a catalyst for action against forms of political, economic, and social oppression deserves our attention. In the first part of this introduction we offer a brief but salient overview on the historiography dedicated to defining fascism and on current debates surrounding the recent rise of the radical right on the world stage. In the second part, we address the relatively smaller attention received by anti-fascism post-1945 and discuss possible reasons for why that has been the case. We conclude by showing how the articles collected in this issue invite us to rethink our definitions of fascism and anti-fascism so that we can better understand our current political time.
Nutrient and sediment loading affect multiple facets of coral functionality in a tropical branching coral
Authors: Becker Danielle M. , Silbiger Nyssa J.
Published: September 2020

Coral reefs, one of the most diverse ecosystems in the world, face increasing pressures from global and local anthropogenic stressors. Therefore, a better understanding of the ecological ramifications of warming and land-based inputs (e.g., sedimentation and nutrient loading) on coral reef ecosystems is necessary. In this study, we measured how a natural nutrient and sedimentation gradient affected multiple facets of coral functionality, including endosymbiont and coral host response variables, holobiont metabolic responses, and percent cover of Pocillopora acuta colonies in Mo'orea, French Polynesia. We used thermal performance curves to quantify the relationship between metabolic rates and temperature along the environmental gradient. We found that algal endosymbiont % nitrogen content, endosymbiont densities, and total chlorophyll a content increased with nutrient input, while endosymbiont nitrogen content cell−1 decreased, likely representing competition among the algal endosymbionts. Nutrient and sediment loading decreased coral metabolic responses to thermal stress in terms of their thermal performance and metabolic rate processes. The acute thermal optimum for dark respiration decreased, along with the maximal performance for gross photosynthetic and calcification rates. Gross photosynthetic and calcification rates normalized to a reference temperature (26.8 °C) decreased along the gradient. Lastly, percent cover of P. acuta colonies decreased by nearly two orders of magnitude along the nutrient gradient. These findings illustrate that nutrient and sediment loading affect multiple levels of coral functionality. Understanding how local-scale anthropogenic stressors influence the responses of corals to temperature can inform coral reef management, particularly on the mediation of land-based inputs into coastal coral reef ecosystems.
Cost of a deprived environment – increased intraspecific aggression and susceptibility to pathogen infections
Authors: Masud Numair , Ellison Amy , Pope Edward C. , Cable Jo
Published: September 2020

A lack of environmental enrichment can be severely detrimental to animal welfare. For terrestrial species, including humans, barren environments are associated with reduced cognitive function and increased stress responses and pathology. Despite a clear link between increased stress and reduced immune function, uncertainty remains on how enrichment might influence susceptibility to disease. For aquatic vertebrates, we are only now beginning to assess enrichment needs. Enrichment deprivation in fish has been linked to increased stress responses, agonistic behaviour, physiological changes and reduced survival. Limited data exist, however, on the impact of enrichment on disease resistance in fish, despite infectious diseases being a major challenge for global aquaculture. Here, using a model vertebrate host-parasite system we investigated the impact of enrichment deprivation on susceptibility to disease, behaviour and physiology. Fish in barren tanks showed significantly higher infection burdens compared to those in enriched enclosures and they also displayed increased intraspecific aggression behaviour. Infections caused hosts to have significantly increased Standard Metabolic Rates compared to uninfected conspecifics, but this did not differ between enriched and barren tanks. This study highlights the universal physiological cost of parasite infection and the biological cost (increased susceptibility to infection and increased aggression) of depriving captive animals of environmental enrichment.
Internal state transition to switch behavioral strategies in cricket phonotaxis behavior
Authors: Hommaru Naoto , Shidara Hisashi , Ando Noriyasu , Ogawa Hiroto
Published: September 2020

Animals employ multiple behavioral strategies for exploring food and mating partners based on both their internal state and external environment. Here, we examined how cricket phonotaxis, which was considered an innate reactive behavior of females to approach the calling song of conspecific males, depended on these internal and external conditions. Our observation revealed that the phonotaxis process consisted of two distinctive phases: wandering and approaching. In the latter phase, crickets moved straightly and directly toward the sound source. The transition into this phase, referred to as the ‘approach phase’, was based on changes in animal's internal state. Moreover, retention of the approach phase required recognition of the calling song while song loss downregulated cricket mobility and induced frequent stopping. This is a typical movement in local search behaviors. Our results indicate that phonotaxis is not only a reactive response but a complicated process including multiple behavioral strategies.
Synthesis of 1,8,13-Substituted Triptycenes
Authors: Iwata Takayuki , Shindo Mitsuru
Published: September 2020

Triptycene is an aromatic compound with D3h symmetry, where three benzene rings are fused to a bicyclo[2.2.2]octatriene skeleton. 1,8,13-Substituted triptycenes exhibit interesting structural features: the C-1,8,13 substituents and the bridgehead C-9 position are located in the same plane. Three faces of the molecule are open for interesting interactions and applications. This paper summarizes the syntheses of 1,8,13-substituted triptycenes.
Mobbing as the Importmant Problem of Employment of Youth in Modern Conditions
Authors: Makshakov E. , Zaharov N.
Published: September 2020

The paper presents the problems associated with youth employment under the current conditions of the formation of the labor market. This topic is relevant, since young people are a huge resource of any country and their problems must be solved first, and sometimes they do not pay due attention. In the course of the work, several definitions are presented and the necessary definition is derived for understanding youth as a social group in the labor market. Data are also presented that prove the existence of these problems. A special form of mobbing is considered - “office bullying” - the humiliation of young new employees. Reasons for mobbing are revealed. The typical goal of the mobbing initiators is defined - to increase their informal status by humiliating others. A typical reason for the humiliation of young new workers can also be due to established traditions based on stereotypes and an involuntary attempt by employees to maintain their status by humiliating new workers.
Methodological Features of Preparation for Solving Economic Problems of the Unified State Exam in Mathematics
Authors: Vlasov Dmitriy , Sinchukov Aleksandr
Published: September 2020

The article focuses on the substantive features of the economic tasks of the unified state examination in mathematics and the methodological features of preparing schoolchildren to solve them. The necessity and methodological expediency of these tasks in the structure of the profile exam in mathematics is justified. Special attention is paid to the formalization process - the first and mandatory stage of solving mathematical problems of economic content, as well as solving problems in various ways with the possibility of the student choosing a rational method of solving. Typical errors of students when working with economic tasks of the unified state examination in mathematics arising at different stages of educational and cognitive activity are highlighted. Recommendations for mathematics teachers are presented, the observance of which helps to overcome these mistakes and difficulties of students. Disaggregated and methodically characterized methods of solving one of the economic problems of the unified state examination in mathematics can be extended to tasks of different types and various socio-economic content. An important place in the system of presented methods is the vector-coordinate method and the method of using the properties of functions - traditionally not sufficiently applied in the school course of mathematics, but fully accessible to high school pupils. The selected methodological features of preparation for solving economic problems can be useful for improving the system of preparation of schoolchildren for passing the unified state examination in mathematics, as well as for updating the content of vocational guidance work with high school pupils.
Alternative Teaching Classes in Chemistry as a Way to Increase Student Motivation to Learn
Authors: Yarkova T. , Rabadanova R.
Published: September 2020

Currently, much attention is paid to the development of students ' intellectual abilities. This problem is particularly acute in Universities that provide training in the applied bachelor's degree system. The use of interactive and alternative types of educational activities is proposed, which increases the motivation for learning, stimulates search and research activities. On the example of the chemical block of disciplines, a scheme for building a training course that includes alternative types of classes is proposed. Methods that improve the quality of education are considered; control points that allow you to evaluate the dynamics of learning the discipline.
The Effects of Operational and Financial Performance Failure on BI&A-Enabled Search Behaviors: A Theory of Performance-Driven Search
Authors: Anand Abhijith , Sharma Rajeev , Kohli Rajiv
Published: September 2020

Abstract for Practice and Policy
Alice no País das Maravilhas e a importância do estudo da literatura inglesa infantil no desenvolvimento do ensino-aprendizagem da criança
Authors: Marinho Batista Coelho Ana Paula , Dutra Bandoli Giselda Maria , Ribeiro Marinho José Ignacio , Netto Joseani Adalemar
Published: September 2020

O presente artigo foi dividido em três seções: a primeira discute acerca da importância da leitura na primeira idade como auxílio na aprendizagem da criança; a segunda aborda as diferenças entre as palavras alfabetização e letramento; e, por fim, na terceira e última seção, foi realizada uma análise sobre a obra “Alice no País das Maravilhas”, de Lewis Carroll, trazendo à baila uma breve biografia dele. Algumas das referências bibliográficas utilizadas: Bagno (2009); Cagliari (2002); Carroll (2012); Soares (2004); Souza (1995); Vigotski (2001), dentre outros.