bluuebunny/crossref_metadata_2025 huggingface dataset:
Monkeying around with venom: an increased resistance to α-neurotoxins supports an evolutionary arms race between Afro-Asian primates and sympatric cobras
Authors: Harris Richard J. , Nekaris K. Anne-Isola , Fry Bryan G.
Published: November 2021

Background

Snakes and primates have a multi-layered coevolutionary history as predators, prey, and competitors with each other. Previous work has explored the Snake Detection Theory (SDT), which focuses on the role of snakes as predators of primates and argues that snakes have exerted a selection pressure for the origin of primates’ visual systems, a trait that sets primates apart from other mammals. However, primates also attack and kill snakes and so snakes must simultaneously avoid primates. This factor has been recently highlighted in regard to the movement of hominins into new geographic ranges potentially exerting a selection pressure leading to the evolution of spitting in cobras on three independent occasions.

Results

Here, we provide further evidence of coevolution between primates and snakes, whereby through frequent encounters and reciprocal antagonism with large, diurnally active neurotoxic elapid snakes, Afro-Asian primates have evolved an increased resistance to α-neurotoxins, which are toxins that target the nicotinic acetylcholine receptors. In contrast, such resistance is not found in Lemuriformes in Madagascar, where venomous snakes are absent, or in Platyrrhini in the Americas, where encounters with neurotoxic elapids are unlikely since they are relatively small, fossorial, and nocturnal. Within the Afro-Asian primates, the increased resistance toward the neurotoxins was significantly amplified in the last common ancestor of chimpanzees, gorillas, and humans (clade Homininae). Comparative testing of venoms from Afro-Asian and American elapid snakes revealed an increase in α-neurotoxin resistance across Afro-Asian primates, which was likely selected against cobra venoms. Through structure-activity studies using native and mutant mimotopes of the α-1 nAChR receptor orthosteric site (loop C), we identified the specific amino acids responsible for conferring this increased level of resistance in hominine primates to the α-neurotoxins in cobra venom.

Conclusion

We have discovered a pattern of primate susceptibility toward α-neurotoxins that supports the theory of a reciprocal coevolutionary arms-race between venomous snakes and primates.
Diagnostic accuracy of pooling urine, anorectal, and oropharyngeal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae: a systematic review and meta-analysis
Authors: Aboud Lily , Xu Yangqi , Chow Eric P. F. , Wi Teodora , Baggaley Rachel , Mello Maeve B. , Fairley Christopher K. , Ong Jason J.
Published: November 2021

Background

Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at genital and extragenital sites is needed for most key populations, but molecular diagnostic tests for CT/NG are costly. We aimed to determine the accuracy of pooled samples from multiple anatomic sites from one individual to detect CT/NG using the testing of a single sample from one anatomic site as the reference.

Methods

In this systematic review and meta-analysis, we searched five databases for articles published from January 1, 2000, to February 4, 2021. Studies were included if they contained original data describing the diagnostic accuracy of pooled testing compared with single samples, resource use, benefits and harms of pooling, acceptability, and impact on health equity. We present the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. The study protocol is registered in PROSPERO, an international database of prospectively registered systematic reviews (CRD42021240793). We used GRADE to evaluate the quality of evidence.

Results

Our search yielded 7814 studies, with 17 eligible studies included in our review. Most studies were conducted in high-income countries (82.6%, 14/17) and focused on men who have sex with men (70.6%, 12/17). Fourteen studies provided 15 estimates for the meta-analysis for CT with data from 5891 individuals. The pooled sensitivity for multisite pooling for CT was 93.1% [95% confidence intervals (CI) 90.5–95.0], I2=43.3, and pooled specificity was 99.4% [99.0–99.6], I2=52.9. Thirteen studies provided 14 estimates for the meta-analysis for NG with data from 6565 individuals. The pooled sensitivity for multisite pooling for NG was 94.1% [95% CI 90.9–96.3], I2=68.4, and pooled specificity was 99.6% [99.1–99.8], I2=83.6. Studies report significant cost savings (by two thirds to a third).

Conclusion

Multisite pooled testing is a promising approach to improve testing coverage for CT/NG in resource-constrained settings with a small compromise in sensitivity but with a potential for significant cost savings.
Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway
Authors: Liu Xingyun , Yang Jia , Yang Chengwei , Huang Xiang , Han Mingming , Kang Fang , Li Juan
Published: November 2021

Background

Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer.

Methods

Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment.

Results

Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells.

Conclusion

Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.
Analysis of pir gene expression across the Plasmodium life cycle
Authors: Little Timothy S. , Cunningham Deirdre A. , Vandomme Audrey , Lopez Carlos Talavera , Amis Sarah , Alder Christopher , Addy John W. G. , McLaughlin Sarah , Hosking Caroline , Christophides George , Reid Adam J. , Langhorne Jean
Published: November 2021

Background

Plasmodium interspersed repeat (pir) is the largest multigene family in the genomes of most Plasmodium species. A variety of functions for the PIR proteins which they encode have been proposed, including antigenic variation, immune evasion, sequestration and rosetting. However, direct evidence for these is lacking. The repetitive nature of the family has made it difficult to determine function experimentally. However, there has been some success in using gene expression studies to suggest roles for some members in virulence and chronic infection.

Methods

Here pir gene expression was examined across the life cycle of Plasmodium berghei using publicly available RNAseq data-sets, and at high resolution in the intraerythrocytic development cycle using new data from Plasmodium chabaudi.

Results

Expression of pir genes is greatest in stages of the parasite which invade and reside in red blood cells. The marked exception is that liver merozoites and male gametocytes produce a very large number of pir gene transcripts, notably compared to female gametocytes, which produce relatively few. Within the asexual blood stages different subfamilies peak at different times, suggesting further functional distinctions. Representing a subfamily of its own, the highly conserved ancestral pir gene warrants further investigation due to its potential tractability for functional investigation. It is highly transcribed in multiple life cycle stages and across most studied Plasmodium species and thus is likely to play an important role in parasite biology.

Conclusions

The identification of distinct expression patterns for different pir genes and subfamilies is likely to provide a basis for the design of future experiments to uncover their function.
Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study
Authors: Wang Xin-Yuan , Ma Tian-Le , Chen Kang-Ning , Pang Zhi-Ying , Wang Hao , Huang Jun-Ming , Qi Guo-Bin , Wang Chen-Zhong , Jiang Zeng-Xin , Gong Lin-Jing , Wang Zhe , Jiang Chang , Yan Zuo-Qin
Published: November 2021

Background

Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH.

Methods

Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments.

Results

In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes.

Conclusions

The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.
MicroRNA 146a is associated with diabetic complications in type 1 diabetic patients from the EURODIAB PCS
Authors: Barutta Federica , Corbetta Beatrice , Bellini Stefania , Guarrera Simonetta , Matullo Giuseppe , Scandella Michela , Schalkwijk Casper , Stehouwer Coen D. , Chaturvedi Nish , Soedamah-Muthu Sabita S. , Durazzo Marilena , Gruden Gabriella
Published: November 2021

Background

MicroRNA-146a-5p (miR-146a-5p) is a key regulator of inflammatory processes. Expression of miR-146a-5p is altered in target organs of diabetic complications and deficiency of miR-146a-5p has been implicated in their pathogenesis. We investigated if serum miR-146a-5p levels were independently associated with micro/macrovascular complications of type 1 diabetes (DM1).

Methods

A nested case–control study from the EURODIAB PCS of 447 DM1 patients was performed. Cases (n = 294) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. Total RNA was isolated from all subjects and miR-146a-5p levels measured by qPCR. Both the endogenous controls U6 snRNA and the spike (Cel-miR-39) were used to normalize the results. Logistic regression analysis was carried out to investigate the association of miR-146a-5p with diabetes complications.

Results

MiR-146a-5p levels were significantly lower in cases [1.15 (0.32–3.34)] compared to controls [1.74 (0.44–6.74) P = 0.039]. Logistic regression analysis showed that levels of miR-146a-5p in the upper quartile were inversely associated with reduced odds ratio (OR) of all complications (OR 0.34 [95% CI 0.14–0.76]) and particularly with cardiovascular diseases (CVD) (OR 0.31 [95% CI 0.11–0.84]) and diabetic retinopathy (OR 0.40 [95% CI 0.16–0.99]), independently of age, sex, diabetes duration, A1c, hypertension, AER, eGFR, NT-proBNP, and TNF-α.

Conclusions

In this large cohort of DM1 patients, we reported an inverse and independent association of miR-146a-5p with diabetes chronic complications and in particular with CVD and retinopathy, suggesting that miR-146a-5p may be a novel candidate biomarker of DM1 complications.
Perceived satisfaction with HIV care and its association with adherence to antiretroviral therapy and viral suppression in the African Cohort Study
Authors: Somi Nancy , Dear Nicole , Reed Domonique , Parikh Ajay , Lwilla Anange , Bahemana Emmanuel , Khamadi Samoel , Iroezindu Michael , Kibuuka Hannah , Maswai Jonah , Crowell Trevor A. , Owuoth John , Maganga Lucas , Polyak Christina , Ake Julie , Esber Allahna ,   the AFRICOS Study Group
Published: November 2021

Background

Increased availability of HIV care over the past decade has dramatically reduced morbidity and mortality among people living with HIV (PLWH) in sub-Saharan Africa. However, perceived and experienced barriers to care, including dissatisfaction with services, may impact adherence and viral suppression. We examined the associations between satisfaction with HIV care and antiretroviral therapy (ART) adherence and viral load suppression.

Methods

The African Cohort Study (AFRICOS) is a prospective observational study conducted at PEPFAR-supported clinics in four African countries. At enrollment and twice-yearly study visits, participants received a clinical assessment and a socio-behavioral questionnaire was administered. Participants were classified as dissatisfied with care if they reported dissatisfaction with any of the following: waiting time, health care worker skills, health care worker attitudes, quality of clinic building, or overall quality of care received. Robust Poisson regression was used to estimate prevalence ratios and 95% confidence intervals (CIs) for associations between satisfaction with care and ART adherence and between satisfaction with care and viral suppression (viral load < 1000 copies/mL).

Results

As of 1 March 2020, 2928 PLWH were enrolled and 2311 had a year of follow-up visits. At the first annual follow-up visit, 2309 participants responded to questions regarding satisfaction with quality of care, and 2069 (89.6%) reported satisfaction with care. Dissatisfaction with waiting time was reported by 177 (7.6%), building quality by 59 (2.6%), overall quality of care by 18 (0.8%), health care worker attitudes by 16 (0.7%), and health care worker skills by 15 (0.7%). After adjusting for age and site, there was no significant difference in viral suppression between those who were satisfied with care and those who were dissatisfied (aPR: 1.03, 95% CI 0.97–1.09). Satisfaction with HIV care was moderately associated with ART adherence among AFRICOS participants (aPR: 1.09; 95% CI 1.00–1.16).

Conclusions

While patient satisfaction in AFRICOS was high and the association between perceived quality of care and adherence to ART was marginal, we did identify potential target areas for HIV care improvement, including reducing clinic waiting times.
Home-based (virtual) rehabilitation improves motor and cognitive function for stroke patients: a randomized controlled trial of the Elements (EDNA-22) system
Authors: Wilson Peter H. , Rogers Jeffrey M. , Vogel Karin , Steenbergen Bert , McGuckian Thomas B. , Duckworth Jonathan
Published: November 2021

Background

Home-based rehabilitation of arm function is a significant gap in service provision for adult stroke. The EDNA-22 tablet is a portable virtual rehabilitation-based system that provides a viable option for home-based rehabilitation using a suite of tailored movement tasks, and performance monitoring via cloud computing data storage. The study reported here aimed to compare use of the EDNA system with an active control (Graded Repetitive Arm Supplementary Program—GRASP training) group using a parallel RCT design.

Methods

Of 19 originally randomized, 17 acute-care patients with upper-extremity dysfunction following unilateral stroke completed training in either the treatment (n = 10) or active control groups (n = 7), each receiving 8-weeks of in-home training involving 30-min sessions scheduled 3–4 times weekly. Performance was assessed across motor, cognitive and functional behaviour in the home. Primary motor measures, collected by a blinded assessor, were the Box and Blocks Task (BBT) and 9-Hole Pegboard Test (9HPT), and for cognition the Montreal Cognitive Assessment (MoCA). Functional behaviour was assessed using the Stroke Impact Scale (SIS) and Neurobehavioural Functioning Inventory (NFI).

Results

One participant from each group withdrew for personal reasons. No adverse events were reported. Results showed a significant and large improvement in performance on the BBT for the more-affected hand in the EDNA training group, only (g = 0.90). There was a mild-to-moderate effect of training on the 9HPT for EDNA (g = 0.55) and control (g = 0.42) groups, again for the more affected hand. In relation to cognition, performance on the MoCA improved for the EDNA group (g = 0.70). Finally, the EDNA group showed moderate (but non-significant) improvement in functional behaviour on the SIS (g = 0.57) and NFI (g = 0.49).

Conclusion

A short course of home-based training using the EDNA-22 system can yield significant gains in motor and cognitive performance, over and above an active control training that also targets upper-limb function. Intriguingly, these changes in performance were corroborated only tentatively in the reports of caregivers. We suggest that future research consider how the implementation of home-based rehabilitation technology can be optimized. We contend that self-administered digitally-enhanced training needs to become part of the health literacy of all stakeholders who are impacted by stroke and other acquired brain injuries.

Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12619001557123. Registered 12 November 2019, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378298&isReview=true
Integrating network pharmacological and experimental models to investigate the therapeutic effects of baicalein in glaucoma
Authors: Yang Jiawei , Zhang Mingxu , Song Qiuyi , Li Siqi , Zhao Xiulan , Kan Liping , Zhu Siquan
Published: November 2021

Background

Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism.

Methods

Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation.

Results

The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin–eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma.

Conclusion

By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.
Landscape of transcription termination in Arabidopsis revealed by single-molecule nascent RNA sequencing
Authors: Mo Weipeng , Liu Bo , Zhang Hong , Jin Xianhao , Lu Dongdong , Yu Yiming , Liu Yuelin , Jia Jinbu , Long Yanping , Deng Xian , Cao Xiaofeng , Guo Hongwei , Zhai Jixian
Published: November 2021

Background

The dynamic process of transcription termination produces transient RNA intermediates that are difficult to distinguish from each other via short-read sequencing methods.

Results

Here, we use single-molecule nascent RNA sequencing to characterize the various forms of transient RNAs during termination at genome-wide scale in wildtype Arabidopsis and in atxrn3, fpa, and met1 mutants. Our data reveal a wide range of termination windows among genes, ranging from ~ 50 nt to over 1000 nt. We also observe efficient termination before downstream tRNA genes, suggesting that chromatin structure around the promoter region of tRNA genes may block pol II elongation. 5′ Cleaved readthrough transcription in atxrn3 with delayed termination can run into downstream genes to produce normally spliced and polyadenylated mRNAs in the absence of their own transcription initiation. Consistent with previous reports, we also observe long chimeric transcripts with cryptic splicing in fpa mutant; but loss of CG DNA methylation has no obvious impact on termination in the met1 mutant.

Conclusions

Our method is applicable to establish a comprehensive termination landscape in a broad range of species.
Exploring reasons for recruitment failure in clinical trials: a qualitative study with clinical trial stakeholders in Switzerland, Germany, and Canada
Authors: Briel Matthias , Elger Bernice S. , McLennan Stuart , Schandelmaier Stefan , von Elm Erik , Satalkar Priya
Published: November 2021

Background

Poor participant recruitment is the most frequent reason for premature discontinuation of randomized clinical trials (RCTs), particularly if they are investigator-initiated. The aims of this qualitative study were to investigate (1) the views of clinical trial stakeholders from three different countries regarding reasons for recruitment failure in RCTs and (2) how these compare and contrast with the causes identified in a previous systematic review of RCT publications.

Methods

From August 2015 to November 2016, we conducted 49 semi-structured interviews with a purposive sample of clinical trial stakeholders. This included investigators based in Germany (n = 9), Switzerland (n = 6) and Canada (n = 1) with personal experience of a discontinued RCT and 33 other stakeholders (e.g., representatives of ethics committees, clinical trial units, pharmaceutical industry) in Switzerland. Individual semi-structured qualitative interviews were conducted and analyzed using thematic analysis.

Results

Interviewees identified a total of 29 different reasons for recruitment failure. Overoptimistic recruitment estimates, too narrow eligibility criteria, lack of engagement of recruiters/trial team, lack of competence/training/experience of recruiters, insufficient initial funding, and high burden for trial participants were mentioned most frequently. The interview findings largely confirm the previous systematic review on published reasons for recruitment failure. However, eight new reasons for recruitment failure were identified in the interviews, which led to the checklist of reasons for recruitment failure being revised and a new category describing research environment-related factors being added.

Conclusions

This study highlights the diversity of often interlinked reasons for recruitment failure in RCTs. Integrating the findings of this interview study with a previous systematic review of RCT publications led to a comprehensive, structured checklist of empirically-informed reasons for recruitment failure. The checklist may be useful to guide further research on interventions to improve participant recruitment in RCTs and helpful for trial investigators, research ethics committees, and funding agencies when assessing trial feasibility with respect to recruitment.
A core outcome set for clinical trials of first- and second-degree perineal tears prevention and treatment: a study protocol for a systematic review and a Delphi survey
Authors: Xiao Lin , Shi Lei , Liu Suting , Luo Yuanyuan , Tian Jinhui , Zhang Lili
Published: November 2021

Background

Perineal tear is a common consequence of vaginal births affecting females globally. Even mild perineal tears could cause short- and long-term complications for females. Though many studies of interventions to prevent or treat perineal tears to minimize the consequences have been conducted, there is a significant heterogeneity in the outcomes measured and reported in existing studies, which makes meaningful comparison difficult and makes the generalizability to clinical practice challenging. Developing a core outcome set (COS) could solve these methodological concerns. In this paper, we report a protocol to develop a COS for clinical trials of mild perineal tears, which shall assist in establishing the evidence base and implementation of effective measures to reduce the incidence and minimize the consequences of mild perineal tears.

Methods/design

The development of this COS will be guided by a study advisory group composed of obstetricians, midwives, nursing managers, service users, and methodologists. This study will include four stages: (1) a systematic research of the literature to identify outcomes reported in prior studies, (2) a semi-structured interview with key stakeholders to collect their opinions on important outcomes, (3) a panel of experts will be invited to conduct a three-round Delphi survey to prioritize these outcomes, and (4) a consensus meeting with key stakeholders to determine the list of outcomes included in the final COS.

Discussion

The development of this COS will provide international standards for the outcomes to be collected and reported in all clinical trials and audits of practice, which involve prevention and treatment of first- and second-degree perineal tears for women with vaginal delivery. This will facilitate comparing and contrasting of studies and allow for combining of appropriate studies with the ultimate goal of improved perineal care for women choosing vaginal delivery.

Trial registration

This study was registered in the database of Core Outcome Measures in Effectiveness Trials (COMET) on June11th, 2021 (https://comet-initiative.org/Studies/Details/1884).
Two weeks of twice-daily prism adaptation treatment does not improve posture or gait in Parkinson’s disease: a double-blind randomized controlled trial
Authors: Bultitude Janet H. , Pidgeon Dawna M. , LeBlanc Pauline R. , Jeffreys Charlotte A. , Alexandre Faith P. , Lee Stephen L.
Published: November 2021

Background

Gait difficulties in Parkinson’s disease have been related to problems shifting the center of gravity forward. We previously showed reduced forward stepping latencies for people with Parkinson’s disease after one session of adaptation to upward visual shifts, which produces downward motor after-effects and potentially shifts the center of gravity forward. Here we tested if repeated prism adaptation improved gait and postural control in Parkinson’s disease through a parallel, double-blind, randomized, sham-controlled trial.

Methods

We recruited participants with idiopathic Parkinson’s disease aged 40–85 and meeting any one of three clinical criteria: (1) Hoehn and Yahr Stage II.5–IV; (2) scoring > 0 on the gait, freezing of gait, and/or postural stability items of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale; or (3) Timed Up and Go > 12 s. Sealed envelope style randomization allocated participants to two weeks of twice-daily prism adaptation or sham treatment. Participants, care givers, and those assessing the outcomes were blinded to group assignment. Primary outcomes were changes in postural control measured using the Berg Balance Scale and the Limits of Stability, Sensory Organization, and Motor Control tests from the Smart EquiTest system. Secondary outcomes included other physiotherapy and questionnaire measures. Outcomes were assessed at the Dartmouth Hitchcock Medical Center immediately before and after the treatment period, with further long-term postal follow-up over 3 months. Outcomes were analyzed using analyses of variance with follow-up t tests.

Results

Eighteen participants were allocated to undergo prism adaptation, of which sixteen were analyzed. Thirteen participants were allocated to undergo sham treatment, and all were analyzed. The prism adaptation group showed increased forward stepping velocity on the Limits of Stability test (pre: M=2.33, SEM=0.24; post: M=2.88, SEM=0.26; t(15)=3.2, p=.005, d=.819). The sham group showed no such change (pre: M=2.13, SEM=0.22; 1d post: M=2.24, SEM=0.22; t(13)=.636, p=.537, d=.176). However, there were no group differences for any other outcome measures and no indications that prism adaptation produced functional improvements in posture, gait, or activities of daily living.

Conclusions

Prism adaptation does not improve gait or postural control in Parkinson’s disease.

Trial registration

ClinicalTrials.govNCT02380859. Registered prospectively on 5 March 2015.
Cellulosic ethanol production by consortia of Scheffersomyces stipitis and engineered Zymomonas mobilis
Authors: Sun Lingling , Wu Bo , Zhang Zengqin , Yan Jing , Liu Panting , Song Chao , Shabbir Samina , Zhu Qili , Yang Shihui , Peng Nan , He Mingxiong , Tan Furong
Published: November 2021

Background

As one of the clean and sustainable energies, lignocellulosic ethanol has achieved much attention around the world. The production of lignocellulosic ethanol does not compete with people for food, while the consumption of ethanol could contribute to the carbon dioxide emission reduction. However, the simultaneous transformation of glucose and xylose to ethanol is one of the key technologies for attaining cost-efficient lignocellulosic ethanol production at an industrial scale. Genetic modification of strains and constructing consortia were two approaches to resolve this issue. Compared with strain improvement, the synergistic interaction of consortia in metabolic pathways should be more useful than using each one separately.

Results

In this study, the consortia consisting of suspended Scheffersomyces stipitis CICC1960 and Zymomonas mobilis 8b were cultivated to successfully depress carbon catabolite repression (CCR) in artificially simulated 80G40XRM. With this strategy, a 5.52% more xylose consumption and a 6.52% higher ethanol titer were achieved by the consortium, in which the inoculation ratio between S. stipitis and Z. mobilis was 1:3, compared with the Z. mobilis 8b mono-fermentation. Subsequently, one copy of the xylose metabolic genes was inserted into the Z. mobilis 8b genome to construct Z. mobilis FR2, leading to the xylose final-consumption amount and ethanol titer improvement by 15.36% and 6.81%, respectively. Finally, various corn stover hydrolysates with different sugar concentrations (glucose and xylose 60, 90, 120 g/L), were used to evaluate the fermentation performance of the consortium consisting of S. stipitis CICC1960 and Z. mobilis FR2. Fermentation results showed that a 1.56–4.59% higher ethanol titer was achieved by the consortium compared with the Z. mobilis FR2 mono-fermentation, and a 46.12–102.14% higher ethanol titer was observed in the consortium fermentation when compared with the S. stipitis CICC1960 mono-fermentation. Furthermore, qRT-PCR analysis of xylose/glucose transporter and other genes responsible for CCR explained the reason why the initial ratio inoculation of 1:3 in artificially simulated 80G40XRM had the best fermentation performance in the consortium.

Conclusions

The fermentation strategy used in this study, i.e., using a genetically modified consortium, had a superior performance in ethanol production, as compared with the S. stipitis CICC1960 mono-fermentation and the Z. mobilis FR2 mono-fermentation alone. This result showed that this strategy has potential for future lignocellulosic ethanol production.
The role of TGF-β or BMPR2 signaling pathway-related miRNA in pulmonary arterial hypertension and systemic sclerosis
Authors: Xu Bei , Xu Guanhua , Yu Ye , Lin Jin
Published: November 2021

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD), causing death in systemic sclerosis (SSc). The past decade has yielded many scientific insights into microRNA (miRNAs) in PAH and SSc. This growth of knowledge has well-illustrated the complexity of microRNA (miRNA)-based regulation of gene expression in PAH. However, few miRNA-related SSc-PAH were elucidated. This review firstly discusses the role of transforming growth factor-beta (TGF-β) signaling and bone morphogenetic protein receptor type II (BMPR2) in PAH and SSc. Secondly, the miRNAs relating to TGF-β and BMPR2 signaling pathways in PAH and SSc or merely PAH were subsequently summarized. Finally, future studies might develop early diagnostic biomarkers and target-oriented therapeutic strategies for SSc-PAH and PAH treatment.
A phylogeny of the genus Limia (Teleostei: Poeciliidae) suggests a single-lake radiation nested in a Caribbean-wide allopatric speciation scenario
Authors: Spikes Montrai , Rodríguez-Silva Rodet , Bennett Kerri-Ann , Bräger Stefan , Josaphat James , Torres-Pineda Patricia , Ernst Anja , Havenstein Katja , Schlupp Ingo , Tiedemann Ralph
Published: November 2021

Objective

The Caribbean is an important global biodiversity hotspot. Adaptive radiations there lead to many speciation events within a limited period and hence are particularly prominent biodiversity generators. A prime example are freshwater fish of the genusLimia, endemic to the Greater Antilles. Within Hispaniola, nine species have been described from a single isolated site, Lake Miragoâne, pointing towards extraordinary sympatric speciation. This study examines the evolutionary history of theLimiaspecies in Lake Miragoâne, relative to their congeners throughout the Caribbean.

Results

For 12Limiaspecies, we obtained almost complete sequences of the mitochondrial cytochromebgene, a well-established marker for lower-level taxonomic relationships. We included sequences of six furtherLimiaspecies from GenBank (total N  = 18 species). Our phylogenies are in concordance with other published phylogenies ofLimia. There is strong support that the species found in Lake Miragoâne in Haiti are monophyletic, confirming a recent local radiation. Within Lake Miragoâne, speciation is likely extremely recent, leading to incomplete lineage sorting in the mtDNA. Future studies using multiple unlinked genetic markers are needed to disentangle the relationships within the Lake Miragoâne clade.
Recent strategies for enhancing the therapeutic efficacy of stem cells in wound healing
Authors: Zhao Yongqing , Wang Min , Liang Feng , Li Jiannan
Published: November 2021

Skin wound healing is a multi-stage process that depends on the coordination of multiple cells and mediators. Chronic or non-healing wounds resulting from the dysregulation of this process represent a challenge for the healthcare system. For skin wound management, there are various approaches to tissue recovery. For decades, stem cell therapy has made outstanding achievements in wound regeneration. Three major types of stem cells, including embryonic stem cells, adult stem cells, and induced pluripotent stem cells, have been explored intensely. Mostly, mesenchymal stem cells are thought to be an extensive cell type for tissue repair. However, the limited cell efficacy and the underutilized therapeutic potential remain to be addressed. Exploring novel and advanced treatments to enhance stem cell efficacy is an urgent need. Diverse strategies are applied to maintain cell survival and increase cell functionality. In this study, we outline current approaches aiming to improve the beneficial outcomes of cell therapy to better grasp clinical cell transformation.
Physico-chemical characteristics and aflatoxins production of Atractylodis Rhizoma to different storage temperatures and humidities
Authors: Liu Qiutao , Jiang Lingling , Xiao Lihe , Kong Weijun
Published: November 2021

This study aimed to investigate the characteristics, moisture contents, chemical fingerprints changes and aflatoxins accumulation ofAtractylodis rhizomaduring storage, further to determine the optimum temperature and relative humidity conditions. Based on the suitable temperature (20–40 °C) and relative humidity (80–95%), 13 different temperature and humidity conditions were set up by the central composite design-response surface methodology (CCD-RSM) forAspergillus flavus. After inoculation withAspergillus flavusby artificial infection,A. rhizomasamples were stored under normal conditions and 13 different temperature and relative humidity levels. By taking the changes of characteristics, the contents of moisture, chemical fingerprints and aflatoxins as the evaluation indexes forA. rhizomawith or withoutAspergillus flavusfungi to optimize the optimal storage conditions. After storage for 10 days, the color ofA. rhizomawas deepened, the water content and chemical composition increased, and some unknown components were detected. The susceptible condition for aflatoxins production inA. rhizomawas identified at temperature 22–37 °C and relative humidity over 87.5%. Thus, the suitable storage conditions forA. rhizomashould be controlled at temperature below 20 °C and relative humidity less than 85%. This paper screened out the optimum temperature and humidity for the storage ofA. rhizoma. Then, the storage specification forA. rhizomawas proposed, lying technical and data support for the scientific preservation of other food or herbs.
Prevalence and predictors of different patterns of hypertension among adults aged 20–60 years in rural communities of Southeast Nigeria: a cross-sectional study
Authors: Ayogu Rufina N. B. , Ezeh Mmesoma G. , Okafor Adaobi M.
Published: November 2021

Background

Hypertension, a major cardiovascular disease risk factor exists several years without symptoms. Few data exist on prevalence and predictors of hypertension among apparently healthy Nigerian adults. This makes it difficult for policy-makers to concentrate efforts to control emerging health burden of the disease. This study assessed prevalence and predictors of isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and combined systolic and diastolic hypertension (CSDH).

Methods

Cross-sectional survey design was employed in the study of 517 adult participants (20–60 years) in a rural setting. Selection of the respondents was through multistage sampling which involved systematic, proportionate and simple random sampling. Data on socio-demographic characteristics, blood pressure, height, weight, and waist circumference were collected. Frequencies, T-test, analysis of variance and Chi square were used in statistical analysis. Bivariate and multivariate logistic regressions were used to evaluate variables associated with different patterns of hypertension with significance accepted at P < 0.05. Frequencies, percentages, crude and adjusted odd ratios were reported. Statistical Product and Service Solutions version 21.0 was used in statistical analysis.

Results

ISH (10.6%), IDH (18.2%) and CSDH (37.8%) were observed among the participants. ISH was less likely among 20–29 year-olds (adjusted odds ratio (aOR) = 0.35, 95% confidence interval (C.I.) = 0.13–0.94), 30–39 year-olds (aOR = 0.30, 95% C.I. = 0.11–0.82) and those with abdominal obesity (aOR = 0.12, 95% C.I. = 0.03–0.56). Participants who perceived their health status as good (aOR = 3.80, 95% C.I. = 1.29–11.18) and excellent (aOR = 5.28, 95% C.I. = 1.54–18.07) were respectively 3.80 and 5.28 times more likely to have ISH. Those with secondary education had significantly higher likelihood for IDH (aOR = 2.05, 95% = 1.02–4.14) whereas self-perceived poor health status (aOR = 0.24, 95% C.I. = 0.09–0.65), absence of obesity (aOR = 0.10, 95% C.I. = 0.01–0.81) and general obesity (aOR = 0.35, 95% C.I. = 0.17–0.72) were associated with reduced risk for IDH. Secondary (aOR = 0.60, 95% C.I. = 0.36–0.99) and tertiary (aOR = 0.49, 95% C.I. = 0.28–0.85) education were associated with reduced risk for CSDH but combined obesity (aOR = 4.39, 95% C.I. = 2.25–8.58) increased the risk for CSDH by 4.

Conclusion

ISH, IDH and CSDH were problems among the adults with age, obesity, self-perception of good/excellent health status and low education level as significant predictors. Health and nutrition education to prevent comorbidities and cerebrovascular accidents are recommended.
Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy
Authors: Kim Do-Hun , Seo Jin-Myung , Shin Kyung-Ju , Yang Su-Geun
Published: November 2021

Background

Aptamer has been called “chemical antibody” which displays the specific affinity to target molecules compared to that of antibodies and possesses several therapeutic advantages over antibodies in terms of size, accessibility to synthesis, and modification. Based on the attractive properties, aptamers have been interested in many directions and now are emerged as new target-designed cancer drug.

Main body

Currently, new types of aptamers have been reported and attracted many scientists’ interesting. Due to simplicity of chemical modification and ready-made molecular engineering, scientists have developed newly designed aptamers conjugated with a wide range of therapeutics, aptamer-drug conjugates; ApDCs, from chemotherapy to phototherapy, gene therapy, and vaccines. ApDCs display synergistic therapeutic effects in cancer treatment.

Conclusion

In this paper, we reviewed various kinds of ApDCs, i.e., ApDC nucleotide analogs, ApDC by drug intercalation, and ApDC by using chemical linker. Current data prove these ApDCs have sufficient potential to complete clinical development soon. Advanced technology of cancer drug delivery and combination treatment of cancers enables aptamer and conjugated drug (ApDCs) efficient means for targeted cancer treatment that reduces potential toxicity and increases therapeutic efficacy.
Thorium and fetal neural tube defects: an epidemiological evidence from large case-control study
Authors: Wang Bin , Pang Yiming , Zhang Yali , Zhang Le , Ye Rongwei , Yan Lailai , Li Zhiwen , Ren Aiguo
Published: November 2021

Background

Thorium is ubiquitous in the environment and its relationship with birth defects is still under discussion. This study aimed to investigate the associations of maternal exposure to thorium with risk of neural tube defects (NTDs) by using a case–control study, as well as the relationship between thorium exposure and the indoor air pollution from coal combustion.

Methods

This study was conducted in 11 local healthcare hospitals during 2003–2007 in Shanxi and Hebei provinces, China. A total of 774 mothers were included as participants who delivering 263 fetuses with NTDs including 123 with anencephaly, 115 with spina bifida, 18 with encephalocele, and 7 other NTD subtypes (cases), and 511 health fetuses without NTDs (controls). Their hair samples were collected as close as to the occipital posterior scalp, of which those grew from 3 months before to 3 months after conception was cut to measure the thorium concentration by inductively coupled plasma-mass spectrometry.

Results

We found a higher hair thorium concentration in the total NTD cases with 0.901 (0.588–1.382) ng/g hair [median (inter-quartile range)] than that in the controls with a value of 0.621 (0.334–1.058) ng/g hair. Similar results were found for the three concerned NTD subtypes. Maternal hair thorium concentration above its median of the controls was associated with an increased risk of the total NTDs with an adjusted odds ratio of 1.80 [95% confidence interval (CI), 1.23–2.63)] by adjusting for all confounders. There was obvious dose-response relationship between maternal hair thorium concentration and the risk of total NTDs, as well as their two subtypes (i.e. anencephaly and spina bifida). Maternal hair thorium concentration was positive associated with their exposure level to indoor air pollution from coal combustion during cooking.

Conclusions

Overall, our findings revealed that maternal periconceptional thorium exposure was associated with the risk of NTDs in North China. Reducing the coal usage in the household cooking activities may decrease maternal thorium exposure level.

Graphical abstract
Kinetic studies of Ni(II) ions adsorption from aqueous solutions using the blast furnace slag (BF slag)
Authors: Chouchane Toufik , Khireddine Ouahida , Boukari Atmen
Published: November 2021

In this work, we used the blast furnace slag for the nickel adsorption in aqueous solution. The physico-chemical characterization showed that the BF slag consists mainly of the silica, lime, and alumina. The specific surface area of the BF slag grains is of the order of 275.8 m2/g. The optimum elimination parameters are the agitation speed 200 rpm, pH 4.5, the adsorption temperature 20 °C, and particle size between 200 and 500 μm. The adsorption capacity and the efficiency of nickel removal by the BF slag after 90 min of agitation are respectively 53.58 mg/g and 92.7%.

The experimental adsorption data showed that the pseudo-second-order model was the most appropriate in nickel adsorption kinetics; the adsorption isotherm could be described well by the Langmuir model indicating that the process was monolayer, and intra-particle diffusion is not the sole mechanism involved in this process. Thermodynamic study showed that the Ni(II) elimination by BF slag process is spontaneous, exothermic, and less entropic.
Experimental evidence of nonlinear avalanche dynamics of energetic particle modes
Authors: Yu L. M. , Zonca F. , Qiu Z. Y. , Chen L. , Chen W. , Ding X. T. , Ji X. Q. , Wang T. , Wang T. B. , Ma R. R. , Yuan B. S. , Shi P. W. , Li Y. G. , Liu L. , Shi Z. B. , Cao J. Y. , Dong J. Q. , Liu Yi , Yang Q. W. , Xu M.
Published: November 2021

Recent observations in HL-2A tokamak give new experimental evidences of energetic particle mode (EPM) avalanche. In a strong EPM burst, the mode structure propagates radially outward within two hundred Alfvén time, while the frequency of the dominant mode changes self-consistently to maximize wave-particle power exchange and mode growth. This suggests that significant energetic particle transport occurs in this avalanche phase, in agreement with theoretical framework of EPM convective amplification. A simplified relay runner model yields satisfactory interpretations of the measurements. The results can help understanding the nonlinear dynamics of energetic particle driven modes in future burning plasmas, such as ITER.
Periodic wave solution of the Kundu-Mukherjee-Naskar equation in birefringent fibers via the Hamiltonian-based algorithm
Authors: Wang Kang-Jia , Zhu Hong-Wei
Published: November 2021

The Kundu-Mukherjee-Naskar equation can be used to address certain optical soliton dynamics in (

) dimensions. In this paper, we aim to find its periodic wave solution by the Hamiltonian-based algorithm. Compared with the existing results, we found a good agreement, which strongly proves the correctness of the proposed method. Finally, the numerical results are presented in the form of 3-D and 2-D plots. The results in this work are expected to shed a bright light on the study of the periodic wave solution in physics.