bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying late-stage host-seeking behaviour of Anopheles gambiae at the insecticidal net interface using a baited-box bioassay
Authors: Hughes Angela , Foster Geraldine M. , Guy Amy , Matope Agnes , Abe Mayumi , Towers David , McCall Philip J.
Published: April 2020

Background

Insecticide-treated nets (ITNs) are losing efficacy against pyrethroid-resistant malaria vector populations throughout Africa. Safeguarding bed net efficacy, vital for effective malaria control, requires greater knowledge of mosquito–ITN interactions and how this impacts on the mosquito.

Methods

A purpose-built benchtop apparatus with a closed 10 cm cubic chamber (the ‘Baited-box’) was used to video record behaviour of individual free-flying female Anopheles gambiae during approach and blood-feeding on a human hand through untreated nets and ITNs at close range. Time and duration of defined behavioural events, and knockdown and mortality at 1- and 24-h post-exposure respectively, were recorded for pyrethroid susceptible and resistant mosquitoes.

Results

Using three human volunteers differing in relative attractiveness to mosquitoes, 328 mosquitoes were individually tested. There were no significant differences between response rates to ITNs and untreated nets (P > 0.1) or between resistant (Tiassalé) and susceptible (Kisumu) mosquito strains, at untreated nets (P = 0.39) or PermaNet 2.0 (P = 1). The sequence of behavioural events from host-seeking to completion of blood-feeding was consistent in all tests but duration and start time of events involving net contact were reduced or delayed respectively with ITNs. Blood-feeding durations at untreated nets (means from 4.25 to 8.47 min (95% confidence interval (CI) = 3.39–9.89) at 3 human volunteers) were reduced by 37–50% at PermaNet 2.0, in susceptible (mean 2.59–4.72 min, 95% CI = 1.54–5.5, P = < 0.05) and resistant (mean 4.20 min, 95% CI = 3.42–4.97, P = 0.01) strains. Total accumulated net contact was approximately 50% lower at PermaNet and Olyset ITNs (P < 0.0001) in susceptible (two of the three volunteers) and resistant mosquitoes. Times prior to first net contact were similar at untreated nets and ITNs (P > 0.2), and neither ITN type showed detectable spatial repellency. After initial contact, blood-feeding commenced later at Olyset (mean 2.76 min, 95% CI = 1.74–3.76, P = 0.0009) and PermaNet (mean 2.4 min, 95% CI = 1.52–3.33, P = 0.0058) than untreated netting (mean 0.68 min, 95% CI = 0.42–0.94).

Conclusions

The baited box offers a simple method for detailed characterization of mosquito behavioural responses to insecticidal nets, for comparing entomological modes of action between nets and for defining the behavioural responses of particular mosquito strains or populations. The device has potential as a screening assay in the search for novel net treatments and for investigations into behavioural resistance mechanisms.
Healthcare resource utilization in patients on lipid-lowering therapies outside Western Europe and North America: findings of the cross-sectional observational International ChoLesterol management Practice Study (ICLPS)
Authors: Annemans Lieven , Azuri Joseph , Al-Rasadi Khalid , Al-Zakwani Ibrahim , Daclin Veronique , Mercier Florence , Danchin Nicolas
Published: April 2020

Background

Few recent large-scale studies have examined healthcare consumption associated with dyslipidemia in countries outside Western Europe and North America.

Methods

This analysis, from a cross-sectional observational study conducted in 18 countries in Eastern Europe, Asia, Africa, the Middle East and Latin America, evaluated avoidable healthcare consumption (defined as ≥1 hospitalization for cardiovascular reasons or ≥1 visit to the emergency room for any reason in the previous 12 months) in patients receiving stable lipid-lowering therapy (LLT). A total of 9049 patients (aged ≥18 years) receiving LLT for ≥3 months and who had had their low-density lipoprotein cholesterol (LDL-C) value measured on stable LLT in the previous 12 months were enrolled between August 2015 and August 2016. Patients who had received a proprotein convertase subtilisin/kexin type 9 inhibitor in the previous 6 months were excluded. Patients were stratified by cardiovascular risk level using the Systematic Coronary Risk Estimation chart for high-risk countries.

Results

The proportion of patients at their LDL-C goal was 32.1% for very-high risk patients compared with 55.7 and 51.9% for patients at moderate and high cardiovascular risk, respectively. Overall, 20.1% of patients had ≥1 reported hospitalization in the previous 12 months (7.9% for cardiovascular reasons), 35.2% had ≥1 intensive care unit stay and 13.8% visited the emergency room. Avoidable healthcare resource consumption was reported for 18.7% patients overall, and in 27.8, 7.7, 7.7 and 13.2% of patients at very-high, high, moderate and low risk, respectively. Across all risk groups 22.4% of patients not at LDL-C goal and 16.6% of patients at LDL-C goal had avoidable healthcare resource consumption.

Being at very-high cardiovascular risk, having cardiovascular risk factors (including hypertension and smoking), and having factors indicating that the patient may be difficult to treat (including statin intolerance, comorbidities and chronic medication), were independent risk factors for avoidable healthcare resource consumption (all p <0.05).

Conclusions

Healthcare resource consumption associated with adverse clinical outcomes was observed in patients on stable LLT in countries outside Western Europe and North America, particularly those at very-high cardiovascular risk and those who were difficult to treat.
Validation of the Chinese EORTC chronic lymphocytic leukaemia module – application of classical test theory and item response theory
Authors: Dong Dong , Jin Jun , Oerlemans Simone , Yu Siyue , Yang Shenmiao , Zhu Jianfeng , Xu Richard Huan
Published: April 2020

Purpose

The association of chronic lymphocytic leukemia (CLL) with health-related quality of life (HRQoL) is rarely studied globally. This study evaluated the psychometric properties of the EORTC-Chronic Lymphocytic Leukaemia (CLL17 [phase III]) module, a newly developed assessment on CLL patients’ HRQoL, among Chinese CLL patients.

Methods

The Chinese CLL17, comprised of three subscales (symptom burden [SB], physical condition [PC] and worries/fears [WF]), was provided by the developer team through EORTC. A cross-sectional online survey was conducted to collect data. The classical traditional theory (CTT) and the item response theory (IRT) were used to evaluate the psychometric properties of CLL17. Internal consistency reliability was determined by the Cronbach’s alpha and item-total correlation. Dimensionality was verified through confirmatory factor analysis (CFA). Convergent validity was also assessed. The generalized partial credit model was used for the IRT. The difficulty, discrimination, item fit, and differential item functioning (DIF) were calculated to assess the instrument’s psychometric properties.

Results

In all, 318 patients, aged between 26 and 82 years, completed the questionnaire. A good level of internal reliability was achieved (Cronbach’s alpha = 0.92). The item-total correlation coefficient ranged from 0.46 to 0.72. There was a mid-to-high correlation between CLL17 and domains of EQ-5D and QLQ-C30. The IRT model showed a satisfactory homogeneity, item fit and good discrimination of items, except for item 4, 6 and 16 (< 1.0). low information provided by item 16 and 17. SB and PC provided more information with theta > 0, whereas WF provided more information with theta < 0. Item 17 perform inconsistently for respondents from different age groups (DIF).

Conclusion

The EORTC-CLL17 Chinese version shows acceptable reliability and validity, making it a valuable instrument to evaluate the impact on the HRQoL of Chinese CLL patients.
Impact of intramuscular adipose tissue content on short- and long-term outcomes of hepatectomy for colorectal liver metastasis: a retrospective analysis
Authors: Horii Nobutoshi , Sawda Yu , Kumamoto Takafumi , Tsuchiya Nobuhiro , Murakami Takashi , Yabushita Yasuhiro , Honma Yuki , Matsuyama Ryusei , Morioka Daisuke , Akiyama Hirotoshi , Endo Itaru
Published: April 2020

Background

Numerous reports regarding sarcopenia have focused on the quantity of skeletal muscle. In contrast, the impact of the quality of skeletal muscle has not been well investigated.

Methods

A retrospective analysis of 115 patients who underwent initial hepatectomy for colorectal liver metastasis between January 2009 and December 2016 in our hospital was performed. Intramuscular adipose tissue content (IMAC) was used to evaluate the quality of skeletal muscle by analysing computed tomography (CT) images at the level of the umbilicus. The impact of poor skeletal muscle quality on short-term and long-term outcomes after hepatectomy for colorectal liver metastasis was analysed.

Results

Patients were divided into two groups (high IMAC and normal IMAC) according to their IMAC values, and their backgrounds were compared. There were no significant differences in most factors between the two groups. However, both body mass index (P = 0.030) and the incidence of postoperative complications of Clavien-Dindo grade 3 or worse (P = 0.008) were significantly higher in the high-IMAC group. In multivariate analyses, an operative blood loss > 600 ml (P = 0.006) and high IMAC (P = 0.008) were associated with postoperative complications of Clavien-Dindo grade 3 or worse. Overall survival and recurrence-free survival were significantly lower (P < 0.001 and P = 0.045, respectively) in the high-IMAC group than in the normal IMAC group. In multivariate analyses for poor overall survival, high IMAC was associated with poor overall survival (P < 0.001).

Conclusions

IMAC is a prognostic factor for poor short- and long-term outcomes in patients with colorectal liver metastasis.
CD13 as a new tumor target for antibody-drug conjugates: validation with the conjugate MI130110
Authors: Domínguez Juan Manuel , Pérez-Chacón Gema , Guillén María José , Muñoz-Alonso María José , Somovilla-Crespo Beatriz , Cibrián Danay , Acosta-Iborra Bárbara , Adrados Magdalena , Muñoz-Calleja Cecilia , Cuevas Carmen , Sánchez-Madrid Francisco , Avilés Pablo , Zapata Juan M.
Published: April 2020

Background

In the search for novel antibody-drug conjugates (ADCs) with therapeutic potential, it is imperative to identify novel targets to direct the antibody moiety. CD13 seems an attractive ADC target as it shows a differential pattern of expression in a variety of tumors and cell lines and it is internalized upon engagement with a suitable monoclonal antibody. PM050489 is a marine cytotoxic compound tightly binding tubulin and impairing microtubule dynamics which is currently undergoing clinical trials for solid tumors.

Methods

Anti-CD13 monoclonal antibody (mAb) TEA1/8 has been used to prepare a novel ADC, MI130110, by conjugation to the marine compound PM050489. In vitro and in vivo experiments have been carried out to demonstrate the activity and specificity of MI130110.

Results

CD13 is readily internalized upon TEA1/8 mAb binding, and the conjugation with PM050489 did not have any effect on the binding or the internalization of the antibody. MI130110 showed remarkable activity and selectivity in vitro on CD13-expressing tumor cells causing the same effects than those described for PM050489, including cell cycle arrest at G2, mitosis with disarrayed and often multipolar spindles consistent with an arrest at metaphase, and induction of cell death. In contrast, none of these toxic effects were observed in CD13-null cell lines incubated with MI130110. Furthermore, in vivo studies showed that MI130110 exhibited excellent antitumor activity in a CD13-positive fibrosarcoma xenograft murine model, with total remissions in a significant number of the treated animals. Mitotic catastrophes, typical of the payload mechanism of action, were also observed in the tumor cells isolated from mice treated with MI130110. In contrast, MI130110 failed to show any activity in a xenograft mouse model of myeloma cells not expressing CD13, thereby corroborating the selectivity of the ADC to its target and its stability in circulation.

Conclusion

Our results show that MI130110 ADC combines the antitumor potential of the PM050489 payload with the selectivity of the TEA1/8 monoclonal anti-CD13 antibody and confirm the correct intracellular processing of the ADC. These results demonstrate the suitability of CD13 as a novel ADC target and the effectiveness of MI130110 as a promising antitumor therapeutic agent.
Targeting epigenetics in sarcomas through EZH2 inhibition
Authors: Italiano Antoine
Published: April 2020

Soft-tissue sarcomas represent a heterogeneous group of diseases with distinct genetic and clinical features accounting for up to 1% of cancer in adults and 15% of cancer in children. Epithelioid sarcoma is an extremely rare and aggressive tumor affecting young adults that is characterized by loss of INI1 expression. INI1 (SMARCB1, SNF5, BAF47) is a subunit of the SWI/SNF chromatin remodeling complex that opposes the enzymatic function of EZH2. When INI1 loses its regulatory function, EZH2 activity is de-regulated, allowing EZH2 to play a driving, oncogenic role. Tazemetostat, a specific EZH2 inhibitor, has just been approved for patients with advanced epithelioid sarcoma and represents a new therapeutic option in this devastating disease.
Correction to: Down-regulated lncRNA SBF2-AS1 inhibits tumorigenesis and progression of breast cancer by sponging microRNA-143 and repressing RRS1
Authors: Xia Wenfei , Liu Yun , Cheng Teng , Xu Tao , Dong Menglu , Hu Xiaopeng
Published: April 2020

In the original publication of this manuscript [1], RRS1 stands for ‘Ribosome biogenesis regulatory protein homolog’ instead of ‘resistance to ralstonia solanacearum 1’. This mistake appears 4 times in the manuscript.
Vasoplegic syndrome following cardiothoracic surgery—review of pathophysiology and update of treatment options
Authors: Busse Laurence W. , Barker Nicholas , Petersen Christopher
Published: April 2020

Vasoplegic syndrome is a common occurrence following cardiothoracic surgery and is characterized as a high-output shock state with poor systemic vascular resistance. The pathophysiology is complex and includes dysregulation of vasodilatory and vasoconstrictive properties of smooth vascular muscle cells. Specific bypass machine and patient factors play key roles in occurrence. Research into treatment of this syndrome is limited and extrapolated primarily from that pertaining to septic shock, but is evolving with the expanded use of catecholamine-sparing agents. Recent reports demonstrate potential benefit in novel treatment options, but large clinical trials are needed to confirm.
Upfront radical surgery with total mesorectal excision followed by adjuvant FOLFOX chemotherapy for locally advanced rectal cancer (TME-FOLFOX): an open-label, multicenter, phase II randomized controlled trial
Authors: Lee Jii Bum , Kim Han Sang , Jung Inkyung , Shin Sang Joon , Beom Seung Hoon , Chang Jee Suk , Koom Woong Sub , Kim Tae Il , Hur Hyuk , Min Byung Soh , Kim Nam Kyu , Park Sohee , Jeong Seung-Yong , Baek Jeong-Heum , Kim Seon Hahn , Lim Joon Seok , Lee Kang Young , Ahn Joong Bae
Published: April 2020

Background

Preoperative chemoradiotherapy (PCRT) followed by surgery and adjuvant chemotherapy is the current standard treatment for stage II/III rectal cancer. However, radiotherapy in the pelvic area is commonly associated with complications such as anastomotic leakage, sexual dysfunction, and fecal incontinence. Recently, the MERCURY study showed that preoperative high-resolution magnetic resonance imaging (MRI) helped to selectively avoid PCRT. It remains unclear whether PCRT is necessary in patients who can achieve a negative circumferential resection margin (CRM) with surgery alone and in patients with cT1–2N1 or cT3N0 without CRM involvement and lateral lymph node metastasis. This study aims to evaluate the efficacy of upfront radical surgery with total mesorectal excision (TME) followed by adjuvant chemotherapy with folinic acid (or leucovorin), fluorouracil, and oxaliplatin (FOLFOX) versus the current standard treatment in patients with surgically resectable, locally advanced rectal cancer.

Methods

This study, named TME-FOLFOX, is a prospective, open-label, multicenter, phase II randomized trial. Patients with locally advanced rectal cancer will be randomized to receive PCRT followed by TME and adjuvant chemotherapy (arm A) or upfront radical surgery with TME followed by adjuvant FOLFOX chemotherapy (arm B). Clinical stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis will be defined using preoperative MRI. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints include 5-year DFS, local recurrence rate, systemic recurrence rate, cost-effectiveness, and overall survival. We hypothesized that our experimental group (arm B) will have a 3-year DFS of 75% and a non-inferiority margin of 15%.

Discussion

Identifying whether patients require PCRT is one of the critical issues in locally advanced rectal cancer. This study aims to elucidate whether PCRT may not be required for all patients with stage II/III rectal cancer, especially for the MRI-based intermediate-risk group (with cT1–2N1 or cT3N0) without CRM involvement and lateral lymph node metastasis. If the findings indicate that our proposed treatment, which omits PCRT, is non-inferior to the standard treatment, then patients may avoid unnecessary radiation-related toxicity, have a shorter treatment duration, and save on medical costs.

Trial registration

ClinicalTrials.gov, NCT02167321. Registered on 19 June 2014.
Mother And late Preterm Lactation Study (MAPLeS): a randomised controlled trial testing the use of a breastfeeding meditation by mothers of late preterm infants on maternal psychological state, breast milk composition and volume, and infant behaviour and growth
Authors: Dib Sarah , Wells Jonathan C. K. , Fewtrell Mary
Published: April 2020

Background

Late preterm infants suffer from more complications and are less likely to be breastfed compared to term infants and their mothers experience higher levels of stress than mothers with term infants. The physiological or hormonal responses that influence milk ejection, milk production, and/or maternal behaviour are possible mechanisms by which maternal distress could negatively influence breastfeeding success. Maternal mood might also affect infant behaviour (feeding, sleeping, and crying) through changes in milk volume and composition, and consequently breastfeeding success and infant growth. Previous research, using relaxation therapy in 64 Malaysian first-time mothers breastfeeding their full-term infants, demonstrated that the therapy was effective in reducing maternal stress and improving infant growth. We hypothesise that expected benefits are even greater in a more vulnerable population where additional breastfeeding support is especially needed, such as in mothers of late preterm infants.

Methods/design

This protocol describes our randomised controlled trial that tests whether a breastfeeding meditation audio reduces maternal stress in mothers of late preterm infants in London. Home visits will be conducted at 2–3 and 6–8 weeks post-delivery. Participants will be randomised to a control group or an intervention group, where mothers will be asked to listen to a meditation tape on a daily basis while breastfeeding. The main outcomes of the intervention will be maternal stress markers and infant weight Z-score. Potential mediators will be the secondary outcomes and include breast milk macronutrient and hormone levels (ghrelin, leptin, cortisol, and adiponectin), milk volume assessed by 48-h test-weighing, and maternal engagement with the infant. Infant behaviour, including crying and sleeping, and infant appetite will be evaluated. Data about other mediators such as maternal perception of milk supply and salivary oxytocin will be collected.

Discussion

We hypothesise that the use of the breastfeeding meditation will reduce maternal stress and consequently improve infant growth mediated by changes in milk composition and volume and maternal behaviour. This study will allow us to understand the mother–infant factors that influence breastfeeding in late preterm infants and potentially identify a method that could improve mother, infant, and breastfeeding outcomes.

Trial registration

ClinicalTrials.gov,NCT03791749. Registered 1 January 2019.
Synthesis, biological evaluation and molecular docking analysis of vaniline–benzylidenehydrazine hybrids as potent tyrosinase inhibitors
Authors: Iraji Aida , Adelpour Tina , Edraki Najmeh , Khoshneviszadeh Mahsima , Miri Ramin , Khoshneviszadeh Mehdi
Published: April 2020

In this work, 11 novel compounds based on vaniline and benzylidenehydrazine structure were synthesized with various substituents on phenyl aromatic ring of the molecule and evaluated as tyrosinase inhibitors. These new derivatives showed significant anti-tyrosinase activities, among which 4i demonstrated to be the most potent compound, with IC50 values of 1.58 µM . The structure–activity relationship study of the novel constructed analogs was fully discussed. Kinetic study of compound 4i showed uncompetitive inhibition towards tyrosinase. Furthermore, the high potency of 4i was supported theoretically by molecular docking evaluations.
RETRACTED ARTICLE: Molecular investigation and
genetic diversity of Pediculus and Pthirus lice in France
Authors: Amanzougaghene Nadia , Mediannikov Oleg , Ly Tran Duc Anh , Gautret Philippe , Davoust Bernard , Fenollar Florence , Izri Arezki
Published: April 2020

Background

Humans are parasitized by three types of lice: body, head and pubic
lice. As their common names imply, each type colonizes a specific region of the body.
The body louse is the only recognized disease vector. However, an increasing
awareness of head lice as a vector has emerged recently whereas the status of pubic
lice as a vector is not known since it has received little attention.

Methods

Here, we assessed the occurrence of bacterial pathogens in 107 body
lice, 33 head lice and 63 pubic lice from Marseille and Bobigny (France) using
molecular methods.

Results

Results show that all body lice samples belonged to the cytb Clade A whereas head lice samples belonged to Clades
A and B. DNA of Bartonella quintana was detected
in 7.5% of body lice samples and, for the first time to our knowledge, in 3.1% of
pubic lice samples. Coxiella burnetii, which is
not usually associated with transmission by louse, was detected in 3.7% of body lice
samples and 3% of head lice samples. To the best of our knowledge, this is the first
report of C. burnetii in Pediculus lice infesting humans in France. Acinetobacter DNA was detected in 21.5% of body lice samples, 6% of
head lice samples and 9.5% of pubic lice samples. Five species were identified with
A. baumannii being the most prevalent.

Conclusions

Our study is the first to report the presence of B. quintana in pubic lice. This is also the first report of the
presence of DNA of C. burnetii in body lice and
head lice in France. Further efforts on the vectorial role of human lice are needed,
most importantly the role of pubic lice as a disease vector should be further
investigated.
Transovarial transmission of Borrelia spp., Rickettsia spp. and Anaplasma phagocytophilum in Ixodes ricinus under field conditions extrapolated from DNA detection in questing larvae
Authors: Hauck Daniela , Jordan Daniela , Springer Andrea , Schunack Bettina , Pachnicke Stefan , Fingerle Volker , Strube Christina
Published: April 2020

Background

Ixodes ricinus constitutes the main European vector tick for the Lyme borreliosis pathogen Borrelia burgdorferi (sensu lato), the relapsing fever borrelia Borrelia miyamotoi, as well as Anaplasma phagocytophilum and several Rickettsia species. Under laboratory conditions, a transovarial transmission to the next tick generation is described for Rickettsia spp. and Borrelia spp., especially regarding B. miyamotoi, whereas the efficiency of transovarial transfer under field conditions is largely unstudied.

Methods

In order to better estimate the potential infection risk by tick larvae for humans and animals, 1500 I. ricinus larvae from 50 collected “nests” (larvae adhering to the flag in a clumped manner) were individually examined for Borrelia, Rickettsia and A. phagocytophilum DNA using quantitative real-time PCR (qPCR).

Results

Thirty-nine of 50 nests each (78.0%, 95% CI: 64.0–88.5%) were positive for Borrelia spp. and Rickettsia spp. DNA, and in three nests (6.0%, 95% CI: 1.3–16.5%) A. phagocytophilum DNA was detected. Overall, DNA from at least one pathogen could be detected in 90.0% (45/50, 95% CI: 78.2–96.7%) of the nests. Of the 1500 larvae, 137 were positive for Borrelia spp. DNA (9.1%, 95% CI: 7.7–10.7%), 341 for Rickettsia spp. DNA (22.7%, 95% CI: 20.6–24.9%) and three for A. phagocytophilum DNA (0.2%, 95% CI: 0–0.6%). Quantity of Borrelia spp. and Anaplasma spp. DNA in positive larvae was low, with 2.7 × 100Borrelia 5S-23S gene copies and 2.4 × 101A. phagocytophilum msp2/p44 gene copies detected on average, while Rickettsia-positive samples contained on average 5.4 × 102gltA gene copies. Coinfections were found in 66.0% (33/50, 95% CI: 51.2–78.8%) of the nests and 8.6% (38/443, 95% CI: 6.1–11.6%) of positive larvae. In fact, larvae had a significantly higher probability of being infected with Borrelia spp. or Rickettsia spp. when both pathogens were present in the nest.

Conclusions

This study provides evidence for transovarial transmission of Rickettsia spp. and Borrelia spp. in I. ricinus under field conditions, possibly facilitating pathogen persistence in the ecosystem and reducing the dependence on the presence of suitable reservoir hosts. Further studies are needed to prove transovarial transmission and to explain the surprisingly high proportion of nests containing Rickettsia and/or Borrelia DNA-positive larvae compared to infection rates in adult ticks commonly reported in other studies.
Does winter cold really limit the dengue vector Aedes aegypti in Europe?
Authors: Kramer Isabelle M. , Kreß Aljoscha , Klingelhöfer Doris , Scherer Christian , Phuyal Parbati , Kuch Ulrich , Ahrens Bodo , Groneberg David A. , Dhimal Meghnath , Müller Ruth
Published: April 2020

Background

Aedes aegypti is a potential vector for several arboviruses including dengue and Zika viruses. The species seems to be restricted to subtropical/tropical habitats and has difficulties in establishing permanent populations in southern Europe, probably due to constraints during the winter season. The aim of this study was to systematically analyze the cold tolerance (CT) of Ae. aegypti in its most cold-resistant life stage, the eggs.

Methods

The CT of Ae. aegypti eggs was compared with that of Ae. albopictus which is well established in large parts of Europe. By systematically studying the literature (meta-analysis), we recognized that CT has been rarely tested in Ae. aegypti eggs, but eggs can survive at zero and sub-zero temperatures for certain exposure periods. To overcome potential bias from experimental differences between studies, we then conducted species comparisons using a harmonized high-resolution CT measuring method. From subtropical populations of the same origin, the survival (hatching in %) and emergence of adults of both species were measured after zero and sub-zero temperature exposures for up to 9 days (3 °C, 0 °C and − 2 °C: ≤ 9 days; − 6 °C: ≤ 2 days).

Results

Our data show that Ae. aegypti eggs can survive low and sub-zero temperatures for a short time period similar to or even better than those of Ae. albopictus. Moreover, after short sub-zero exposures of eggs of both species, individuals still developed into viable adults (Ae. aegypti: 3 adults emerged after 6 days at − 2 °C, Ae. albopictus: 1 adult emerged after 1 day at − 6 °C).

Conclusions

Thus, both the literature and the present experimental data indicate that a cold winter may not be the preventing factor for the re-establishment of the dengue vector Ae. aegypti in southern Europe.
Use of alternative bioassays to explore the impact of pyrethroid resistance on LLIN efficacy
Authors: Grossman Marissa K. , Oliver Shüné V. , Brooke Basil D. , Thomas Matthew B.
Published: April 2020

Background

There is substantial concern that the spread of insecticide resistance will render long-lasting insecticide-treated nets (LLINs) ineffective. However, there is limited evidence supporting a clear association between insecticide resistance and malaria incidence or prevalence in the field. We suggest that one reason for this disconnect is that the standard WHO assays used in surveillance to classify mosquito populations as resistant are not designed to determine how resistance might impact LLIN efficacy. The standard assays expose young, unfed female mosquitoes to a diagnostic insecticide dose in a single, forced exposure, whereas in the field, mosquitoes vary in their age, blood-feeding status, and the frequency or intensity of LLIN exposure. These more realistic conditions could ultimately impact the capacity of “resistant” mosquitoes to transmit malaria.

Methods

Here, we test this hypothesis using two different assays that allow female mosquitoes to contact a LLIN as they host-seek and blood-feed. We quantified mortality after both single and multiple exposures, using seven different strains of Anopheles ranging in pyrethroid resistance intensity.

Results

We found that strains classified as 1×-resistant to the pyrethroid insecticide deltamethrin in the standard WHO assay exhibited > 90% mortality over 24 h following more realistic LLIN contact. Mosquitoes that were able to blood-feed had increased survival compared to their unfed counterparts, but none of the 1×-resistant strains survived for 12 days post-exposure (the typical period for malaria parasite development within the mosquito). Mosquitoes that were 5×- and 10×-resistant (i.e. moderate or high intensity resistance based on the WHO assays) survived a single LLIN exposure well. However, only about 2–3% of these mosquitoes survived multiple exposures over the course of 12 days and successfully blood-fed during the last exposure.

Conclusions

These results suggest that the standard assays provide limited insight into how resistance might impact LLIN efficacy. In our laboratory setting, there appears little functional consequence of 1×-resistance and even mosquitoes with moderate (5×) or high (10×) intensity resistance can suffer substantial reduction in transmission potential. Monitoring efforts should focus on better characterizing intensity of resistance to inform resistance management strategies and prioritize deployment of next generation vector control products.
Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee
Authors:   for the Paediatric Rheumatology International Trials Organisation (PRINTO), Giancane Gabriella , Swart Joost F. , Castagnola Elio , Groll Andreas H. , Horneff Gerd , Huppertz Hans-Iko , Lovell Daniel J. , Wolfs Tom , Herlin Troels , Dolezalova Pavla , Sanner Helga , Susic Gordana , Sztajnbok Flavio , Maritsi Despoina , Constantin Tamas , Vargova Veronika , Sawhney Sujata , Rygg Marite , K. Oliveira Sheila , Cattalini Marco , Bovis Francesca , Bagnasco Francesca , Pistorio Angela , Martini Alberto , Wulffraat Nico , Ruperto Nicolino
Published: April 2020

Background

To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC).

Methods

The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI.

Results

A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI.

Conclusions

We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies.

Trial registration

Clinicaltrials.govNCT 01399281; ENCePP seal: awarded on 25 November 2011.
SCN2A channelopathies in the autism spectrum of neuropsychiatric disorders: a role for pluripotent stem cells?
Authors: Kruth Karina A. , Grisolano Tierney M. , Ahern Christopher A. , Williams Aislinn J.
Published: April 2020

Efforts to identify the causes of autism spectrum disorders have highlighted the importance of both genetics and environment, but the lack of human models for many of these disorders limits researchers’ attempts to understand the mechanisms of disease and to develop new treatments. Induced pluripotent stem cells offer the opportunity to study specific genetic and environmental risk factors, but the heterogeneity of donor genetics may obscure important findings. Diseases associated with unusually high rates of autism, such as SCN2A syndromes, provide an opportunity to study specific mutations with high effect sizes in a human genetic context and may reveal biological insights applicable to more common forms of autism. Loss-of-function mutations in the SCN2A gene, which encodes the voltage-gated sodium channel NaV1.2, are associated with autism rates up to 50%. Here, we review the findings from experimental models of SCN2A syndromes, including mouse and human cell studies, highlighting the potential role for patient-derived induced pluripotent stem cell technology to identify the molecular and cellular substrates of autism.
Long-chain n-alkane biodegradation coupling to methane production in an enriched culture from production water of a high-temperature oil reservoir
Authors: Chen Jing , Liu Yi-Fan , Zhou Lei , Irfan Muhammad , Hou Zhao-Wei , Li Wei , Mbadinga Serge Maurice , Liu Jin-Feng , Yang Shi-Zhong , Wu Xiao-Lin , Gu Ji-Dong , Mu Bo-Zhong
Published: April 2020

Paraffinic n-alkanes (C22–C30), crucial portions of residual oil, are generally considered to be difficult to be biodegraded owing to their general solidity at ambient temperatures and low water solubility, rendering relatively little known about metabolic processes in different methanogenic hydrocarbon-contaminated environments. Here, we established a methanogenic C22–C30 n-alkane-degrading enrichment culture derived from a high-temperature oil reservoir production water. During two-year incubation (736 days), unexpectedly significant methane production was observed. The measured maximum methane yield rate (164.40 μmol L−1 d−1) occurred during the incubation period from day 351 to 513. The nearly complete consumption (> 97%) of paraffinic n-alkanes and the detection of dicarboxylic acids in n-alkane-amended cultures indicated the biotransformation of paraffin to methane under anoxic condition. 16S rRNA gene analysis suggested that the dominant methanogen in n-alkane-degrading cultures shifted from Methanothermobacter on day 322 to Thermoplasmatales on day 736. Bacterial community analysis based on high-throughput sequencing revealed that members of Proteobacteria and Firmicutes exhibiting predominant in control cultures, while microorganisms affiliated with Actinobacteria turned into the most dominant phylum in n-alkane-dependent cultures. Additionally, the relative abundance of mcrA gene based on genomic DNA significantly increased over the incubation time, suggesting an important role of methanogens in these consortia. This work extends our understanding of methanogenic paraffinic n-alkanes conversion and has biotechnological implications for microbial enhanced recovery of residual hydrocarbons and effective bioremediation of hydrocarbon-containing biospheres.
Silver ion bioreduction in nanoparticles using Artemisia annua L. extract: characterization and application as antibacterial agents
Authors: Aghajanyan Anush , Gabrielyan Lilit , Schubert Robin , Trchounian Armen
Published: April 2020

The biological synthesis of metal nanoparticles using plant extracts with defined size and morphology is a simple, nontoxic and environmentally friendly method. The present study focused on the synthesis of silver nanoparticles (Ag NPs) by Artemisia annua L. extract as reducing and stabilising agent. The Ag NPs function, as antibacterial agents, is with that they are further used in human therapy. The effects of pH and temperature on the synthesis of NPs were characterized by UV-absorption spectroscopy and shown by surface plasmon resonance (SPR) band at 410 nm. NPs’ size and morphology were measured by transmission electron microscopy (TEM) and dynamic light scattering (DLS). TEM images showed that Ag NPs were in a nano-sized range (20–90 nm) and had spherical shape. Our findings demonstrated that lower concentration (100 µg mL−1) of the biogenic Ag NPs exhibited antibacterial activity against Gram-negative Escherichia coli BW 25113 and Gram-positive Enterococcus hirae ATCC 9790.
Discriminative features based on modified log magnitude spectrum for playback speech detection
Authors: Yang Jichen , Xu Longting , Ren Bo , Ji Yunyun
Published: April 2020

In order to improve the performance of hand-crafted features to detect playback speech, two discriminative features, constant-Q variance-based octave coefficients and constant-Q mean-based octave coefficients, are proposed for playback speech detection in this work. They rely on our findings that variance-based modified log magnitude spectrum and mean-based modified log magnitude spectrum can enhance the discriminative power between genuine speech and playback speech. Then constant-Q variance-based octave coefficients (constant-Q mean-based octave coefficients) can be obtained by combining variance-based modified log magnitude spectrum (mean-based modified log magnitude spectrum), octave segmentation, and discrete cosine transform. Finally, constant-Q variance-based octave coefficients and constant-Q mean-based octave coefficients are evaluated on ASVspoof 2017 corpus version 2.0 and ASVspoof 2019 physical access, respectively. Experimental results show that variance-based modified log magnitude spectrum and mean-based modified log magnitude spectrum can produce discriminative features toward playback speech. Further results on the two databases show that constant-Q variance-based octave coefficients and constant-Q mean-based octave coefficients can perform better than some common features, such as mel frequency cepstral coefficients and constant-Q cepstral coefficients.
A lower bound for the area of Plateau foams
Authors: Gimeno Vicent , Markvorsen Steen , Sotoca José M.
Published: April 2020

Real foams can be viewed as geometrically well-organized dispersions of more or less spherical bubbles in a liquid. When the foam is so drained that the liquid content significantly decreases, the bubbles become polyhedral-like and the foam can be viewed now as a network of thin liquid films intersecting each other at the Plateau borders according to the celebrated Plateau’s laws.

In this paper we estimate from below the surface area of a spherically bounded piece of a foam. Our main tool is a new version of the divergence theorem which is adapted to the specific geometry of a foam with special attention to its classical Plateau singularities.

As a benchmark application of our results, we obtain lower bounds for the fundamental cell of a Kelvin foam, lower bounds for the so-called cost function, and for the difference of the pressures appearing in minimal periodic foams. Moreover, we provide an algorithm whose input is a set of isolated points in space and whose output is the best lower bound estimate for the area of a foam that contains the given set as its vertex set.
Tendon regeneration and muscle hypotrophy after isolated Gracilis tendon harvesting - a pilot study
Authors: Flies Anne , Denecke Timm , Kraus Natascha , Kruppa Philipp , Provencher Matthew T. , Becker Roland , Kopf Sebastian
Published: April 2020

Purpose

The gracilis tendon (GT) is a commonly used autologous graft in Orthopaedic surgery. The majority of information on knee function and outcomes after hamstring harvest is related to both semitendinosus and GT harvest. Little is known regarding isolated harvest of a GT. It was hypothesized that isolated GT harvest would lead to altered gait patterns (e.g. augmented anterior-posterior translation or rotation in the tibiofemoral joint) and consequently a higher prevalence of cartilage lesions and meniscal tears in knees.

Methods

GT harvesting was performed on patients with chronic acromioclavicular joint instability without previous knee injuries or surgeries. MRI of both knees and thighs were performed. Knee MRI were evaluated using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Inter- and intraobserver reliabilities, cross-sectional areas of different muscles, fatty infiltration of the gracilis muscle (GM) and GT regeneration were evaluated. The contralateral limb served as reference. The observers were blinded towards the identity of the patients and the operatively treated side.

Results

After a mean time of 44 months after surgery testing was performed on 12 patients. No significant side-to-side differences were found using WORMS, although there was a trend towards increased cartilage lesions after GT harvest (median healthy knee 4.8 and GT harvested knee 7.8p = 0.086).Inter- and intraobserver repeatability was high with 0.899 (95% confidence interval (CI) 0.708–0.960) and 0.988 (95% CI 0.973–0.995), respectively. A significant hypotrophy of the GM with a mean decrease of 25.3%, 18.4% and 16.9% occurred at 25% (p = 0.016), 50% (p = 0.007) and 75% (p = 0.002) of the length of the femur from distal. No compensatory hypertrophy of other thigh muscles or increased fatty infiltration of the GM was found. Tendon regeneration took place in eight out of 12 patients. In case of regeneration, the regenerated tendon inserted in a more proximal place.

Conclusion

Isolated harvest of the GT for shoulder procedures did not affect knee MRI significantly indicating therefore in general suitable graft utilization for surgeries outside of the knee. GT regenerated in most patients with just a more proximal insertion and a hypotrophy of the muscle belly.
Interaction of enzymes with lignocellulosic materials: causes, mechanism and influencing factors
Authors: Baig K. S.
Published: April 2020

For the production of biofuel (bioethanol), enzymatic adsorption onto a lignocellulosic biomass surface is a prior condition for the enzymatic hydrolysis process to occur. Lignocellulosic substances are mainly composed of cellulose, hemicellulose and lignin. The polysaccharide matrix (cellulose and hemicellulose) is capable of producing bioethanol. Therefore, lignin is removed or its concentration is reduced from the adsorption substrates by pretreatments. Selected enzymes are used for the production of reducing sugars from cellulosic materials, which in turn are converted to bioethanol. Adsorption of enzymes onto the substrate surface is a complicated process. A large number of research have been performed on the adsorption process, but little has been done to understand the mechanism of adsorption process. This article reviews the mechanisms of adsorption of enzymes onto the biomass surfaces. A conceptual adsorption mechanism is presented which will fill the gaps in literature and help researchers and industry to use adsorption more efficiently. The process of enzymatic adsorption starts with the reciprocal interplay of enzymes and substrates and ends with the establishment of molecular and cellular binding. The kinetics of an enzymatic reaction is almost the same as that of a characteristic chemical catalytic reaction. The influencing factors discussed in detail are: surface characteristics of the participating materials, the environmental factors, such as the associated flow conditions, temperature, concentration, etc. Pretreatment of lignocellulosic materials and optimum range of shear force and temperature for getting better results of adsorption are recommended.
Systematic characterization of the ubiquitin-specific proteases in Magnaporthe oryzae
Authors: Cai Xuan , Wang Zhao , Hou Yuxi , Liu Caiyun , Hendy Ahmed , Xing Junjie , Chen Xiao-Lin
Published: April 2020

Ubiquitin-specific protease (UBP) family is the largest group of deubiquitinases, which plays important roles in eukaryotic organisms. Comprehensive analysis ofUBPgenes has not been conducted in the plant pathogenic fungi. In this study, 11 putativeUBPgenes were identified and characterized in the rice blast fungusMagnaporthe oryzae. Expression profile analysis showed thatUBP3,UBP6,UBP12andUBP14were highly expressed in different tissues ofM. oryzae. In allubpmutants, especially Δubp3, Δubp12and previously reported Δubp14,the ubiquitination levels were evidently elevated, which is consistent with their molecular roles in de-ubiquitination. The Δubp1, Δubp3, Δubp4, Δubp8and Δubp14mutants were reduced in colony growth. Most of theubpmutants were severely reduced in conidia production capacity, indicating important roles of theUBPsin conidia formation. Except for Δubp2and Δubp16, all of the other mutants were decreased in virulence to host plants and defective in invasive growth. Theseubpmutants also induced massive ROS accumulation in host cells. We also found that theUBPs may function as both positive and negative regulators in stress response and nutrient utilization ofM. oryzae. Collectively, UBPs are important for development, stress response, nutrient utilization and infection ofM. oryzae.
Effect of drying methods and parameters on the antioxidant properties of tea (Camellia sinensis) leaves
Authors: Roslan A. S. , Ismail A. , Ando Y. , Azlan A.
Published: April 2020

Background

Conventional drying using heated air oven is commonly used as a method for preserving the product but often affects the nutritional value, taste, and texture. However, the heat from the drying method can oxidize and destroy heat-sensitive compounds. Superheated steam (SHS) drying uses superheated steam instead of hot air or combustion gases in a direct dryer and was reported better at preserving the nutritional values of food products.

Aim

To evaluate the effect of SHS drying on antioxidant properties of tea leaves. The study also compared SHS drying with conventional and freeze-drying methods.

Results

Tea leaves dried using freeze drying retained the highest level of antioxidant properties compared to other drying methods. The leaves dried using SHS exhibited significantly higher radical scavenging activity, ORAC and FRAP values compared to oven drying method. At different drying temperatures (150 °C and 175 °C), oven dried leaves showed significantly higher (p < 0.05) antioxidant properties than that of SHS dried ones. Tea leaves dried for 60, 75, and 90 min using SHS showed significantly higher (p < 0.05) FRAP and ORAC values, and also total phenolic content compared to oven dried tea leaves.

Conclusion

Tea leaves dried using SHS drying method retained higher level of antioxidant properties compared to oven drying. The drying method also retained lower antioxidant properties as drying time increased. Further study involving SHS drying in food-related fields should be conducted to support its usefulness.

Graphical abstract