bluuebunny/crossref_metadata_2025 huggingface dataset:
T-LAK cell-originated protein kinase (TOPK) enhances androgen receptor splice variant (ARv7) and drives androgen-independent growth in prostate cancer
Authors: Alhawas Lama , Amin Karishma S , Salla Bharath , Banerjee Partha P
Published: November 2020

Despite impressive advances in the treatment of prostate cancer with various efficacious inhibitors along the androgen/androgen receptor axis, eventual development of incurable metastatic Castration-Resistant Prostate Cancer (mCRPC) is inevitable and remains a major clinical challenge. Constitutively active androgen receptor (AR) spliced variants have emerged as primary means of resistance to anti-androgens and androgen synthesis inhibitors. The alternatively spliced AR variant, ARv7, has attracted significant interest due to its constitutively active status in CRPC that drives androgen-independence. Factors that are involved in regulating ARv7 levels in CRPC are not clearly known. We recently demonstrated that a protein kinase, T-LAK cell-originated protein kinase (TOPK) level correlates with the aggressiveness of prostate cancer and its invasive behavior. In this study, we investigated whether TOPK plays a role in driving androgen-independence in prostate cancer cells. Our data demonstrate that TOPK overexpression in androgen-dependent LNCaP and VCaP induces ARv7 and drives androgen-independent growth. On the other hand, pharmacological inhibition of TOPK in androgen-independent LNCaP95 and 22Rv1 represses AR transactivation, and AR stability. In summary, this study illustrates a direct role of TOPK in regulating ARv7 and driving androgen-independence in prostate cancer cells.
Infective endocarditis complicating COVID-19 pneumonia: a case report
Authors: Spinoni Enrico Guido , Degiovanni Anna , Della Corte Francesco , Patti Giuseppe
Published: November 2020

Background

During the COVID-19 outbreak, cardiovascular imaging, especially transoesophageal echocardiography (TOE), may expose healthcare personnel to virus contamination and should be performed only if strictly necessary. On the other hand, transthoracic echocardiography (TTE) and TOE represent the first-line imaging exams for the diagnosis of infective endocarditis (IE). To date, this is the first case of COVID-19 complicated by IE.

Case summary

We present the case of a 57-year-old man with severe COVID-19 pneumonia requiring mechanical ventilation. During the intensive care unit (ICU) stay, he developed fever and positive haemocoltures for methicillin-resistant Staphylococcus aureus infection. TTE did not identify endocardial vegetations. TOE was then performed and outlined IE of the aortic valve on the non-coronary cusp. Antibiotic therapy was given with progressive resolution of the septic state and improvement of inflammatory signs. After 30 days of ICU stay, the patient was transferred to the Sub-ICU and then to a rehabilitation hospital. A close follow-up has been scheduled: after full recovery, a new echocardiography will be performed (TTE and TOE, if the former is non-conclusive) to consider surgical valve repair in the case of persistence/progression of the valvular lesion or deterioration of the valve function.

Discussion

In COVID-19 patients, echocardiography remains the leading imaging exam for the diagnosis of IE. If the suspicion of IE is high, even in this setting of patients, TTE or TOE (if TTE is non-conclusive) are mandatory. A high degree of attention must be paid and appropriate preventive measures taken to avoid contamination of healthcare personnel.
Zinc finger proteins in the host-virus interplay: multifaceted functions based on their nucleic acid-binding property
Authors: Wang Guanming , Zheng Chunfu
Published: November 2020

Zinc finger proteins (ZFPs) are a huge family comprised of massive, structurally diverse proteins characterized by zinc ion coordinating. They engage in the host-virus interplay in-depth and occupy a significant portion of the host antiviral arsenal. Nucleic acid-binding is the basic property of certain ZFPs, which draws increasing attention due to their immense influence on viral infections. ZFPs exert multiple roles on the viral replications and host cell transcription profiles by recognizing viral genomes and host mRNAs. Their roles could be either antiviral or proviral and were separately discussed. Our review covers the recent research progress and provides a comprehensive understanding of ZFPs in antiviral immunity based on their DNA/RNA binding property.
Refrigeration temperature enhanced synergistic interaction of curcumin and 460 nm light-emitting diode against Staphylococcus saprophyticus at neutral pH
Authors: Wang Ziyuan , Han Lin , Liu Jie , Yao Mingfei
Published: November 2020

Objectives

As considered highly resistant to antibiotics like mecillinam, the rise of Staphylococcus saprophyticus (S. saprophyticus) contamination of fresh foods and food processing environments necessitates the development of a new antimicrobial approach for food safety control. This study aimed to investigate the synergistic effect of food-grade curcumin (CUR) and blue light-emitting diode (LED) on S. saprophyticus.

Materials and Methods

S. saprophyticus was subjected to the synergistic treatment at 4 and 25 °C. The influence of parameters, including CUR concentration, light dose, and pH incubation time on the inactivation of S. saprophyticus was characterized through plate counting method.

Results: 

The combined treatment of CUR and blue light irradiation significantly (P < 0.05) reduced bacterial counts and the antimicrobial effect was in a CUR concentration and light dose-dependent manner. Moreover, refrigeration temperature (4 °C) significantly (P < 0.05) enhanced the antibacterial effect at neutral pH condition (6.2–7.2), resulting in approximately 6.0 log reductions. Under acidic condition (pH 2.2–5.2), there was no significant difference in bacterial population reduction between treatments at both temperatures.

Conclusions

These findings proposed that synergistic interaction of CUR and 460 nm LED under refrigerated temperature could enhance the inactivation of S. saprophyticus at neutral pH condition.
An adaptive BDF2 implicit time-stepping method for the phase field crystal model
Authors: Liao Hong-lin , Ji Bingquan , Zhang Luming
Published: November 2020

An adaptive BDF2 implicit time-stepping method is analyzed for the phase field crystal model. The suggested method is proved to preserve a modified energy dissipation law at the discrete levels when the time-step ratios satisfy $r_k:=\tau _k/\tau _{k-1}<3.561$, which is the zero-stability restriction of the variable-step BDF2 scheme for ordinary differential equations. With the help of discrete orthogonal convolution kernels and corresponding convolution inequalities, an optimal $L^2$ norm error estimate is established under the weak step-ratio restriction $0<r_k<3.561$ to ensure energy stability. As far as we know, this is the first time that such an error estimate is theoretically proved for a nonlinear parabolic equation. Based on tests on random temporal meshes an effective adaptive time-stepping strategy is suggested to efficiently capture the multi-scale behavior and accelerate the numerical simulations.
Beyond Fecal Microbiota Transplantation: Developing Drugs from the Microbiome
Authors: Gerardin Ylaine , Timberlake Sonia , Allegretti Jessica R , Smith Mark B , Kassam Zain
Published: November 2020

The transfer of live gut microbes may transform patient care across a range of autoimmune, metabolic, hepatic, and infectious diseases. One early approach, fecal microbiota transplantation, has shown promise in Clostridiodes difficile infection and the potential for improving clinical and public health outcomes for other antibiotic-resistant bacteria. These clinical successes have motivated the development of microbiome drugs, which will need to address challenges in safety, uniformity, and delivery while seeking to preserve the benefits of using whole microbiome communities as novel therapeutics and an innovative platform for drug discovery.
Fumigant Toxicity and Oviposition Deterrent Activity of Volatile Constituents from Asari Radix et Rhizoma against Phthorimaea operculella (Lepidoptera: Gelechiidae)
Authors: Wu Mei , Xiong Yan , Han Rui , Dong Wenxia , Xiao Chun
Published: November 2020

Phthorimaea operculella (Zeller) is a worldwide pest of potato. Plant-borne chemicals would be potential alternatives of synthetic chemical fumigants against P. operculella in the storage. Asari Radix et Rhizoma is derived from the dry roots and rhizomes of Asarum heterotropoides Fr. Schmidt var. mandshuricum, A. sieboldii Miq. var. seoulense, or A. sieboldii. In this study, fumigant toxicity and oviposition deterrent of volatile constituents from ARR, δ-3-carene, γ-terpinene, terpinolene, eucarvone, 3,5-dimethoxytoluene, and methyleugenol were tested against P. operculella. The preliminary verification of preventive and control effects of eucarvone, 3,5-dimethoxytoluene and methyleugenol on P. operculella was carried out by simulating warehouse experiments. The results indicated that the six compounds above had fumigation toxic effects on the adults and eggs of P. operculella. Among them, δ-3-carene, γ-terpinene, and terpinolene had weaker fumigation effects than those of eucarvone, 3,5-dimethoxytoluene, and methyleugenol. The LC50 values of eucarvone, 3,5-dimethoxytoluene, and methyleugenol against adult P. operculella were 1.01, 1.78, 1.51 mg/liter air, respectively. The LC50 values against egg P. operculella were 1.09, 0.55, 0.30 mg/liter air, respectively. The oviposition deterrent experiment showed that only methyleugenol (at 5 and 1 mg/ml) and eucarvone (5 mg/ml) had a substantial oviposition deterrent effect. The simulated warehouse experiment verified that methyleugenol, eucarvone, and 3,5-dimethoxytoluene protected potatoes from P. operculella and demonstrated that methyleugenol had the best preventive and control effects. It was concluded that methyleugenol was the active ingredient with the most potential in the volatiles from ARR on P. operculella control and merit further study as botanic fumigant.
A surveillance study of patterns of reirradiation practice using external beam radiotherapy in Japan
Authors: Yamazaki Hideya , Suzuki Gen , Aibe Norihiro , Nakamura Satoaki , Yoshida Ken , Oh Ryoongjin ,   JReRT Group
Published: November 2020

The aim of this study was to survey the present status and patterns of reirradiation (Re-RT) practice using external beam radiotherapy in Japan. We distributed an e-mail questionnaire to the Japanese Society for Radiation Oncology partner institutions, which consisted of part 1 (number of Re-RT cases in 2008–2012 and 2013–2018) and part 2 (indications and treatment planning for Re-RT and eight case scenarios). Of the 85 institutions that replied to part 1, 75 (88%) performed Re-RTs. However, 59 of these 75 institutions (79%) reported difficulty in obtaining Re-RT case information from their databases. The responses from 37 institutions included the number of Re-RT cases, which totaled 508 in the period from 2009 to 2013 (institution median 3; 0–235), and an increase to 762 cases in the period from 2014 to 2018 (12.5; 0–295). A total of 47 physicians responded to part 2 of the survey. Important indications for Re-RT that were considered were age, performance status, life expectancy, absence of distant metastases and time interval since previous radiotherapy. In addition to clinical decision-making factors, previous total radiation dose, volume of irradiated tissue and the biologically equivalent dose were considered during Re-RT planning. From the eight site-specific scenarios presented to the respondents, >60% of radiation oncologists agreed to perform Re-RT. Re-RT cases have increased in number, and interest in Re-RT among radiation oncologists has increased recently due to advances in technology. However, several problems exist that emphasize the need for consensus building and the establishment of guidelines for practice and prospective evaluation.
V772 Cas: an ellipsoidal HgMn star in an eclipsing binary
Authors: Kochukhov O , Johnston C , Labadie-Bartz J , Shetye S , Ryabchikova T A , Tkachenko A , Shultz M E
Published: November 2020

The late B-type star V772 Cas (HD 10260) was previously suspected to be a rare example of a magnetic chemically peculiar star in an eclipsing binary system. Photometric observations of this star obtained by the TESS satellite show clear eclipses with a period of 5.0137 d accompanied by a significant out-of-eclipse variation with the same period. High-resolution spectroscopy reveals V772 Cas to be an SB1 system, with the primary component rotating about a factor two slower than the orbital period and showing chemical peculiarities typical of non-magnetic HgMn chemically peculiar stars. This is only the third eclipsing HgMn star known and, owing to its brightness, is one of the very few eclipsing binaries with chemically peculiar components accessible to detailed follow-up studies. Taking advantage of the photometric and spectroscopic observations available for V772 Cas, we performed modelling of this system with the phoebe code. This analysis provided fundamental parameters of the components and demonstrated that the out-of-eclipse brightness variation is explained by the ellipsoidal shape of the evolved, asynchronously rotating primary. This is the first HgMn star for which such variability has been definitively identified.
New measurements of the cyclotron line energy in Cen X-3
Authors: Tomar Gunjan , Pradhan Pragati , Paul Biswajit
Published: November 2020

We report results from the analysis of data from two observations of the accreting binary X-ray pulsar Cen X-3 carried out with the broad-band X-ray observatories Suzaku and NuSTAR. The pulse profile is dominated by a broad single peak and show some energy dependence with two additional weak pulse peaks at energies below 15 and 25 keV, respectively. The broad-band X-ray spectrum for 0.8–60.0 keV for Suzaku  and 3.0–60.0 keV for NuSTAR is fitted well with high-energy cut-off power-law model along with soft-excess, multiple iron emission lines and a cyclotron absorption. The cyclotron line energy is found to be $30.29^{+0.68}_{-0.61}$ and $29.22^{+0.28}_{-0.27}$ keV, respectively, in the Suzaku  and NuSTAR  spectra. We make a comparison of these two measurements with four previous measurements of Cyclotron Resonant Scattering Feature (CRSF) in Cen X-3  obtained with Ginga, BeppoSAX,  and RXTE. We find no evidence for a dependence of the CRSF on luminosity. Except for one CRSF measurement with BeppoSAX , the remaining measurements are consistent with a CRSF energy in the range of 29.5–30.0 keV over a luminosity range of 1.1–5.4 × 1037 erg s−1 different from several other sources that show considerable CRSF variation in the same luminosity range.
Night-time monitoring of the aerosol content of the lower atmosphere by differential photometry of the anthropogenic skyglow
Authors: Kocifaj Miroslav , Bará Salvador
Published: November 2020

Night-time monitoring of the aerosol content of the lower atmosphere is a challenging task, because appropriate reference natural light sources are lacking. Here, we show that the anthropogenic night-sky brightness due to city lights can be successfully used for estimating the aerosol optical depth of arbitrarily thick atmospheric layers. This method requires measuring the zenith night-sky brightness with two detectors located at the limiting layer altitudes. Combined with an estimate of the overall atmospheric optical depth (available from ground-based measurements or specific satellite products), the ratio of these radiances provides a direct estimate of the differential aerosol optical depth of the air column between these two altitudes. These measurements can be made with single-channel low-cost radiance detectors widely used by the light pollution research community.
Telomere length in peripheral blood lymphocytes related to genetic variation in telomerase, prognosis and clinicopathological features in breast cancer patients
Authors: Kroupa Michal , Rachakonda Sivaramakrishna , Vymetalkova Veronika , Tomasova Kristyna , Liska Vaclav , Vodenkova Sona , Cumova Andrea , Rossnerova Andrea , Vodickova Ludmila , Hemminki Kari , Soucek Pavel , Kumar Rajiv , Vodicka Pavel
Published: November 2020

Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and 154 healthy controls using the monochrome multiplex quantitative Polymerase Chain Reaction assay. In addition, we genotyped nine TL-associated single-nucleotide polymorphisms that had been identified through genome-wide association studies. Our results showed that the patients had significantly (P = 0.001, Mann–Whitney U-test) longer LTL [median (interquartile range); 1.48 (1.22–1.78)] than the healthy controls [1.27 (0.97–1.82)]. Patients homozygous (CC) for the common allele of hTERT rs2736108 or the variant allele (CC) of hTERC rs16847897 had longer LTL. The latter association remained statistically significant in the recessive genetic model after the Bonferroni correction (P = 0.004, Wilcoxon two-sample test). We observed no association between LTL and overall survival or relapse-free survival of the patients. LTL did not correlate with cancer staging based on Union for International Cancer Control (UICC), The tumor node metastasis (TNM) staging system classification, tumour grade or molecular BC subtypes. Overall, we observed an association between long LTL and BC disease and an association of the hTERC rs16847897 CC genotype with increased LTL. However, no association between LTL, clinicopathological features and survival of the patients was found.
Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back
Authors: Kharel Prakash , Becker Gertraud , Tsvetkov Vladimir , Ivanov Pavel
Published: November 2020

Guanine-quadruplexes (G4s) are non-canonical four-stranded structures that can be formed in guanine (G) rich nucleic acid sequences. A great number of G-rich sequences capable of forming G4 structures have been described based on in vitro analysis, and evidence supporting their formation in live cells continues to accumulate. While formation of DNA G4s (dG4s) within chromatin in vivo has been supported by different chemical, imaging and genomic approaches, formation of RNA G4s (rG4s) in vivo remains a matter of discussion. Recent data support the dynamic nature of G4 formation in the transcriptome. Such dynamic fluctuation of rG4 folding-unfolding underpins the biological significance of these structures in the regulation of RNA metabolism. Moreover, rG4-mediated functions may ultimately be connected to mechanisms underlying disease pathologies and, potentially, provide novel options for therapeutics. In this framework, we will review the landscape of rG4s within the transcriptome, focus on their potential impact on biological processes, and consider an emerging connection of these functions in human health and disease.
Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study
Authors: Sahebjam Solmaz , Forsyth Peter A , Tran Nam D , Arrington John A , Macaulay Robert , Etame Arnold B , Walko Christine M , Boyle Theresa , Peguero Edwin N , Jaglal Michael , Mokhtari Sepideh , Enderling Heiko , Raghunand Natarajan , Gatewood Tyra , Long Wendy , Dzierzeski Jennifer L , Evernden Brittany , Robinson Timothy , Wicklund Melissa C , Kim Sungjune , Thompson Zachary J , Chen Dung-Tsa , Chinnaiyan Prakash , Yu Hsiang-Hsuan Michael
Published: November 2020

Background

Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs).

Methods

Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W.

Results

Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46–18.46) and 7.92 months (95% CI: 6.31–12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97–18.86) with a median PFS of 6.54 months (95% CI: 5.95–18.86). The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%.

Conclusions

The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.
Procedural skill needs for Canadian paediatricians: A national profile
Authors: White Jessica , Rowan-Legg Anne , Writer Hilary , Chanchlani Rahul , Gupta Ronish
Published: November 2020

Background and Objectives

Procedural practice by paediatricians in Canada is evolving. Little empirical information is available on the procedural competencies required of general paediatricians. Accordingly, the aim of this study was to conduct a needs assessment of Canadian general paediatricians to identify procedural skills required for practice, with the goal of informing post-graduate and continuing medical education.

Methods

A survey was sent to paediatricians through the Canadian Paediatric Surveillance Program (CPSP) (www.cpsp.cps.ca/surveillance). In addition to demographic information about practice type and location, participants were asked to indicate the frequency with which they performed each of 32 pre-selected procedures and whether each procedure was considered essential to their practice.

Results

The survey response rate was 33.2% (938/2,822). Data from participants who primarily practice general paediatrics were analyzed (n=481). Of these, 71.0% reported performing procedures. The most frequently performed procedures were: bag-valve-mask ventilation of an infant, lumbar puncture, and ear curettage, being performed monthly by 40.8%, 34.1%, and 27.7% of paediatricians, respectively. The procedures performed by most paediatricians were also those found most essential to practice, with a few exceptions. Respondents performed infant airway procedures with greater frequency and rated them more essential when compared to the same skill performed on children. We found a negative correlation between procedures being performed and difficulty maintaining proficiency in a skill.

Conclusions

This report of experiences from Canadian general paediatricians suggests a wide variability in the frequency of procedural performance. It helps establish priorities for post-graduate and continuing professional medical education curricula in the era of competency-based medical education.
Patients’ and rheumatologists’ perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis—an international survey within the GLORIA study
Authors: Santiago T , Voshaar M , de Wit M , Carvalho P D , Buttgereit F , Cutolo M , Paolino S   , Castelar Pinheiro G R , Boers M , Da Silva J A P
Published: November 2020

Objective

To evaluate the current perspectives of patients and health professionals regarding the efficacy and safety of low-dose glucocorticoids (GCs) in RA.

Methods

Two online surveys were disseminated to patients and health professionals, in their native language, through national patient organizations and national rheumatology medical societies, respectively. SurveyMonkey®, MediGuard.org and the Glucocorticoid Low-dose Outcome in RA Study (GLORIA) website were used to offer and deliver these surveys.

Results

A total of 1221 RA patients with exposure to GCs, and 414 rheumatologists completed the surveys. Patients and rheumatologists reported high levels of agreement regarding the efficacy of low-dose GCs: at least 70% considered that they are very rapid and effective in the control of signs and symptoms of RA. However, half of the patients also reported having suffered serious adverse events with GCs, and 83% described concerns about safety. The majority of rheumatologists estimated that endocrine, ophthalmologic and cutaneous adverse events affect >4% of all patients treated with low-dose GCs for 2 years, based on a heat map.

Conclusions

RA patients with self-reported exposure to GCs express high levels of satisfaction with low-dose GCs efficacy, as do rheumatologists. However, both expressed excessive concerns regarding the safety of GCs (greatly exceeding the published evidence data), which may compromise the optimal use of this medication. This study indicates that there is an unmet need for appropriately designed prospective trials that shed light on the real risk associated with low-dose GCs, as well as a need for renovated educational programs on the real benefits and harms of low-dose GCs, for both patients and physicians.
Residual, differential neurobehavioral deficits linger after multiple recovery nights following chronic sleep restriction or acute total sleep deprivation
Authors: Yamazaki Erika M , Antler Caroline A , Lasek Charlotte R , Goel Namni
Published: November 2020

Study Objectives

The amount of recovery sleep needed to fully restore well-established neurobehavioral deficits from sleep loss remains unknown, as does whether the recovery pattern differs across measures after total sleep deprivation (TSD) and chronic sleep restriction (SR).

Methods

In total, 83 adults received two baseline nights (10–12-hour time in bed [TIB]) followed by five 4-hour TIB SR nights or 36-hour TSD and four recovery nights (R1–R4; 12-hour TIB). Neurobehavioral tests were completed every 2 hours during wakefulness and a Maintenance of Wakefulness Test measured physiological sleepiness. Polysomnography was collected on B2, R1, and R4 nights.

Results

TSD and SR produced significant deficits in cognitive performance, increases in self-reported sleepiness and fatigue, decreases in vigor, and increases in physiological sleepiness. Neurobehavioral recovery from SR occurred after R1 and was maintained for all measures except Psychomotor Vigilance Test (PVT) lapses and response speed, which failed to completely recover. Neurobehavioral recovery from TSD occurred after R1 and was maintained for all cognitive and self-reported measures, except for vigor. After TSD and SR, R1 recovery sleep was longer and of higher efficiency and better quality than R4 recovery sleep.

Conclusions

PVT impairments from SR failed to reverse completely; by contrast, vigor did not recover after TSD; all other deficits were reversed after sleep loss. These results suggest that TSD and SR induce sustained, differential biological, physiological, and/or neural changes, which remarkably are not reversed with chronic, long-duration recovery sleep. Our findings have critical implications for the population at large and for military and health professionals.
A pilot trial of a transdiagnostic treatment for emotional disorders—a locally adapted variant of group Unified Protocol (UP) for Chinese adults
Authors: Powell Candice L Y M , Farchione Todd J , Barlow David H , Leung Patrick W L
Published: November 2020

There has been increasing interest in transdiagnostic cognitive-behavioral therapy (CBT), which is more cost efficient yet yields similar effect sizes when compared to disorder-specific CBT. The Unified Protocol (UP) for Transdiagnostic Treatment of Emotional Disorders was adapted for Hong Kong Chinese adults with common mental disorders, such as depression and anxiety. It was piloted in community settings and delivered in a group format. Thirty-one Chinese adults (female = 93.5%, mean age = 44 years) with heterogeneous anxiety and depressive disorders were recruited from a number of public-funded community mental health centers in Hong Kong to participate in a pilot trial of a locally adapted variant of UP. Treatment consisted of 14 group sessions plus one individual session. Each group included six to nine participants. The diagnostic and outcome measures included Anxiety Disorders Interview Schedule for DSM-IV, The Chinese versions of Beck Depression Inventory-Revised (C-BDI-II), Beck Anxiety Inventory (C-BAI), Positive Affect subscale of Positive and Negative Affect Scale, and Work and Social Adjustment Scale. Results indicate significant improvement across a number of outcome measures, with moderate-to-large effect sizes for measures of depression (d = 1.11), anxiety (d = 0.67), positive affect (d = 0.54), and work and social functioning (d = 0.49). Furthermore, 45.2% and 29.0% of the participants scored within the normal range of C-BDI-II and C-BAI at posttreatment, respectively, compared to 3.2% and 6.5% at pretreatment. This pilot, uncontrolled trial demonstrated potential effectiveness of a locally adapted variant of group UP for Chinese adults with common mental disorders. It achieved comparable effect sizes to those observed in western populations.
European Consumer Law after the New Deal: A Tryptich
Authors: Grochowski Mateusz
Published: November 2020

In 2018/2019, EU private law experienced one of the most vigorous and meaningful changes in its evolution so far. The prominence of this alteration does not rest solely on the number of new rules, but—more importantly—on the substantially new perspective on economic and social tasks of European private law. The reform encompassed three core areas: consumer protection, sustainability and digital commerce. The paper seeks to better understand the transformative task of private law in the social and economic realm. The protection of the environment, on the one hand, and the informational autonomy and privacy, on the other, provide a new type of challenge for the existing agenda of private law, reaching beyond economic efficiency as its ultimate goal. Finally, the emergence of digitalization and sustainability as the new domains of private law reinvigorates the question of to what extent the European private law should directly engage itself in pursuing the social and economic agenda. The 2018/2019 legislation opened a new chapter in this discussion, facing private law with a new genre of tasks, which traditionally belonged to the domain of public ordering. The paper seeks to unpack the essence of this change by focusing on three intertwined issues: vulnerability, autonomy, and regulation. Mingled together they seem to form the backbone of the reform, which seems to provide an in-depth subversion of the existing conceptual structures of EU consumer law.
Parallel evolution of toepads in rock-dwelling lineages of a terrestrial gecko (Gekkota: Gekkonidae:Heteronotia binoei)
Authors: Riedel Jendrian , Zozaya Stephen M , Hoskin Conrad J , Schwarzkopf Lin
Published: November 2020

Selection for effective locomotion can lead to specialized morphological structures. Adhesive toepads, which have arisen independently in different lizard clades, facilitate the use of vertical and inverted substrates. Their evolution is poorly understood because functionally intermediate morphological configurations between padless and pad-bearing forms are rare. To shed light on toepad evolution, we assessed the subdigital morphology of phylogenetically distinct lineages of the Bynoe’s gecko species complex (Heteronotia binoei). Most populations of H. binoei are terrestrial, but two relatively distantly related saxicoline (rock-dwelling) lineages have enlarged terminal subdigital scales resembling toepads. We reconstructed the ancestral terminal subdigital scale size of nine lineages of H. binoei in eastern Australia, including these two saxicoline lineages. Additionally, we compared the subdigital microstructures of four lineages: the two saxicoline lineages and their respective terrestrial sister-lineages. Surprisingly, all four lineages had fully developed setae, but the setae of the two saxicoline lineages were significantly longer, branched more often and were more widely spaced than the terrestrial sister-lineages. We conclude that the saxicoline lineages represent examples of parallel evolution of enlarged adhesive structures in response to vertical substrate use, and their morphology represents a useful model as an intermediate state in toepad evolution.
Molecular phylogeny of the Orthurethra (Panpulmonata: Stylommatophora)
Authors: Saadi Ahmed J , Mordan Peter B , Wade Christopher M
Published: November 2020

We have undertaken a molecular analysis of the Orthurethra, one of the major groups of stylommatophoran land snails and slugs. Approximately 4000 nucleotides of the rRNA gene cluster [5.8S, internal transcribed spacer 2 (ITS2) and almost the full-length large subunit (LSU; 28S) gene] were sequenced for 40 orthurethran genera belonging to 19 families. Our phylogeny recovers three well-supported clades within the Orthurethra; the Azecidae, Chondrinidae + Truncatellinidae, and a main clade comprising all remaining orthurethran families. The first division in the Orthurethra separates the Azecidae from all other orthurethran taxa. Of those families represented by more than one genus, the Achatinellidae, Azecidae, Cerastidae, Partulidae and Vertiginidae are recovered as strongly supported monophyletic units, whereas the Chondrinidae, Enidae, Pupillidae and Valloniidae are unsupported in the tree. Although there is relatively little support for the deep-level relationships among the main orthurethran groups, some groupings are strongly supported. The sister-group relationship of the Cochlicopidae with the Amastridae is strongly supported in our molecular analyses, and there is also some support for the grouping of the Orculidae with the Pyramidulidae, and the Draparnaudiidae with the Gastrocoptidae. The findings of our molecular analyses support dividing the Orthurethra into three superfamilies: the Azecoidea, Chondrinoidea and Pupilloidea.
Causal inference gates corticostriatal learning
Authors: Dorfman Hayley M. , Tomov Momchil , Cheung Bernice , Clarke Dennis , Gershman Samuel J. , Hughes Brent L.
Published: November 2020

Attributing outcomes to your own actions or to external causes is essential for appropriately learning which actions lead to reward and which actions do not. Our previous work showed that this type of credit assignment is best explained by a Bayesian reinforcement learning model which posits that beliefs about the causal structure of the environment modulate reward prediction errors (RPEs) during action value updating. In this study, we investigated the neural circuits underlying reinforcement learning that are influenced by causal beliefs using functional magnetic resonance imaging (fMRI) while human participants (N = 31; 13 males, 18 females) completed a behavioral task that manipulated beliefs about causal structure. We found evidence that RPEs modulated by causal beliefs are represented in posterior putamen, while standard (unmodulated) RPEs are represented in ventral striatum. Further analyses revealed that beliefs about causal structure are represented in anterior insula and inferior frontal gyrus. Finally, structural equation modeling revealed effective connectivity from anterior insula to posterior putamen. Together, these results are consistent with a neural architecture in which causal beliefs in anterior insula are integrated with prediction error signals in posterior putamen to update action values.

Significance Statement

Learning which actions lead to reward – a process known as reinforcement learning – is essential for survival. Inferring the causes of observed outcomes – a process known as causal inference – is crucial for appropriately assigning credit to one’s own actions and restricting learning to effective action-outcome contingencies. Previous studies have linked reinforcement learning to the striatum and causal inference to prefrontal regions, yet how these neural processes interact to guide adaptive behavior remains poorly understood. Here, we found evidence that causal beliefs represented in the prefrontal cortex modulate action value updating in posterior striatum, separately from the unmodulated action value update in ventral striatum posited by standard reinforcement learning models.
Quantification of Hypoperfusion in Autism Assessed by Diffuse Correlation Spectroscopy and Frequency Domain Near Infrared Spectroscopy
Authors: Rinehart Benjamin , Poon Chien-Sing , Sunar Ulas
Published: November 2020

There is a need for quantitative biomarkers for early diagnosis of autism. We showed previously that hemoglobin concentrations show contrast between autistic group vs control group in humans. Cerebral blood flow can provide additional sensitivity for improved characterization. Diffuse correlation spectroscopy (DCS) has been shown to be reliable method to obtain blood flow contrast in animals and humans. Thus, in this study we evaluated DCS in an established autism model. Our results indicate that autistic group had significantly lower blood flow compared to control group. These results confirm the previous results obtained from humans by positron emission tomography and magnetic resonance imaging.
Lipidomic Profiling Reveals an Age-Related Deficiency of Skeletal Muscle Proresolving Mediators that Contributes to Maladaptive Tissue Remodeling
Authors: Markworth James F. , Brown Lemuel A. , Lim Eunice , Castor-Macias Jesus A. , Larouche Jacqueline , Macpherson Peter C. D. , Davis Carol , Aguilar Carlos A. , Maddipati Krishna Rao , Brooks Susan V.
Published: November 2020

Chronic inflammation and deregulated acute immune cell responses to injury contribute to age-associated skeletal muscle dysfunction. Specialized pro-resolving mediators (SPMs) control inflammation and support myofiber regeneration in young mice, but their role in aging muscle remains unknown. Here we examined the effect of age on the mediator lipidome of skeletal muscle via LC-MS based lipidomic profiling and tested whether systemic administration of the SPM resolvin D1 (RvD1) could limit excessive inflammation and improve the regenerative capacity of aged muscle. Aged mice displayed chronic low-grade muscle inflammation prior to injury and this was associated with a basal deficiency of lipoxygenase (LOX) derived SPMs as well as anti-inflammatory cytochrome P450 (CYP) derived lipid epoxides. Following muscle damage, young and aged mice produced similar amounts of pro-inflammatory cyclooxygenase (COX) and 12-LOX metabolites, but aged mice mounted a markedly deficient SPM response. This was associated with heightened leukocyte recruitment, impaired myofiber regeneration, and delayed recovery of strength. Systemic treatment with RvD1 had minimal impact on excessive myeloid cell infiltration and defective myofiber regeneration in aged mice. Nevertheless, RvD1 treatment did suppress inflammatory cytokines, modulated muscle stem cells, limited maladaptive tissue remodeling, and improved recovery of specific muscle force. We conclude that aging results in a marked deficiency of local SPM biosynthesis within muscle and that immunoresolvents may be attractive novel therapeutics for the treatment of muscular injuries and associated pain in the elderly, due to positive effects on recovery of muscle function without the negative side effects on myofiber regeneration of traditional anti-inflammatory treatments.
Conserved visual capacity of rats under red light
Authors: Nikbakht Nader , Diamond Mathew E.
Published: November 2020

Recent studies examine the behavioral capacities of rats and mice with and without visual input, and the neuronal mechanisms underlying such capacities. These animals are assumed to be functionally blind under red light, an assumption that might originate in the fact that they are dichromats who possess ultraviolet and green but not red cones. But the inability to see red as a color does not necessarily rule out form vision based on red light absorption. We measured Long-Evans rats’ capacity for visual form discrimination under red light of various wavelength bands. Upon viewing a black and white grating, they had to distinguish between two categories of orientation, horizontal and vertical. Psychometric curves plotting judged orientation versus angle demonstrate the conserved visual capacity of rats under red light. Investigations aiming to explore rodent physiological and behavioral functions in the absence of visual input should not assume red-light blindness.
Characterization of the complete mitochondrial genome of the New Zealand parasitic blowflyCalliphora vicina(Insecta: Diptera: Calliphoridae)
Authors: Palevich Nikola , Carvalho Luis , Maclean Paul
Published: November 2020

In the present study, the complete mitochondrial genome of the New Zealand parasitic blowflyCalliphora vicina(blue bottle blowfly) field strain NZ_CalVic_NP was generated using next-generation sequencing technology and annotated. The 16,518 bp mitochondrial genome consists of 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and a 1,689 bp non-coding region, similar to most metazoan mitochondrial genomes. Phylogenetic analysis showed thatC. vicinaNZ_CalVic_NP does not form a monophyletic cluster with the remaining three Calliphorinae species. The complete mitochondrial genome sequence ofC. vicinaNZ_CalVic_NP is a resource to facilitate future species identification research within the Calliphoridae.
High-Throughput Image-Based Plant Stand Count Estimation Using Convolutional Neural Networks
Authors: Khaki Saeed , Pham Hieu , Han Ye , Kent Wade , Wang Lizhi
Published: November 2020

Abstract

The future landscape of modern farming and plant breeding is rapidly changing due to the complex needs of our society. The explosion of collectable data has started a revolution in agriculture to the point where innovation must occur. To a commercial organization, the accurate and efficient collection of information is necessary to ensure that optimal decisions are made at key points of the breeding cycle. However, due to the sheer size of a breeding program and current resource limitations, the ability to collect precise data on individual plants is not possible. In particular, efficient phenotyping of crops to record its color, shape, chemical properties, disease susceptibility, etc. is severely limited due to labor requirements and, oftentimes, expert domain knowledge. In this paper, we propose a deep learning based approach, named DeepStand, for image-based corn stand counting at early phenological stages. The proposed method adopts a truncated VGG-16 network as a backbone feature extractor and merges multiple feature maps with different scales to make the network robust against scale variation. Our extensive computational experiments suggest that our proposed method can successfully count corn stands and out-perform other state-of-the-art methods. It is the goal of our work to be used by the larger agricultural community as a way to enable high-throughput phenotyping without the use of extensive time and labor requirements.
A single QTL with large effect is associated with female functional virginity in an asexual parasitoid wasp
Authors: Ma Wen-Juan , Pannebakker Bart A. , Li Xuan , Geuverink Elzemiek , Anvar Seyed Yahya , Veltsos Paris , Schwander Tanja , van de Zande Louis , Beukeboom Leo W.
Published: November 2020

During the transition from sexual to asexual reproduction, a suite of reproduction-related sexual traits become superfluous, and may be selected against if costly. Female functional virginity refers to asexual females resisting to mate or not fertilizing eggs after mating. These traits appear to be among the first that evolve during the gradual transition from sexual to asexual reproduction. The genetic basis of female functional virginity remains elusive. Previously, we reported that female functional virginity segregates as a single recessive locus in the asexual parasitoid waspAsobara japonica. Here, we investigate the genetic basis of this trait by quantitative trait loci (QTL) mapping and candidate gene analyses. Consistent with the segregation of phenotypes, a single QTL of large effect was found spanning over 4.23 Mb and comprising at least 131 protein-coding genes, of which 15 featured sex-biased expression in the related sexualAsobara tabida. We speculate that two of these 15 genes may be of particular interest:CD151 antigenandnuclear pore complex protein Nup50. Overall, our results are consistent with a single gene or a cluster of linked genes underlying rapid evolution of female functional virginity in the transition to asexuality. Once a mutation for rejection to mate has swept through a population, the region comprising the gene(s) does not get smaller due to lack of recombination in asexuals.
AMycobacterium tuberculosiseffector protein attacks host innate immunity by acting as an unusual ubiquitinating enzyme
Authors: Wang Jing , Ge Pupu , Lei Zehui , Lu Zhe , Qiang Lihua , Chai Qiyao , Zhang Yong , Zhao Dongdong , Li Bingxi , Su Jiaqi , Peng Ruchao , Pang Yu , Shi Yi , Gao George Fu , Qiu Xiao-Bo , Liu Cui Hua
Published: November 2020

Protein kinase G (PknG), a eukaryotic type serine-threonine protein kinase (STPK) inMycobacterium tuberculosis(Mtb), is secreted into the cytosol of infected macrophages to promote intracellular survival of mycobacteria and has been considered as a promising therapeutic target for tuberculosis (TB) treatment. However, the molecular details of Mtb PknG-host intracellular interactions remain obscure. Here, we demonstrate that PknG serves as both the ubiquitin-activating enzyme (E1) and the ubiquitin ligase (E3) to promote ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF–β-activated kinase 1 (TAK1), and thus inhibits the NF-κB-mediated host innate immune responses. Surprisingly, PknG promotes the attachment of ubiquitin (Ub) to ubiquitin-conjugating enzyme (E2) UbcH7 via an isopeptide bond (UbcH7 K82-Ub), instead of a usual C86-Ub thiol-ester bond, and then promotes the discharge of Ub from UbcH7 by acting as an isopeptidase before attaching Ub to its substrates TRAF2 and TAK1. These results demonstrate that Mtb PknG promotes ubiquitination of the key components of the host innate immunity by acting as an unusual ubiquitinating enzyme to suppress innate immunity. Our findings provide a potential TB treatment via targeting unconventional ubiquitinating activities of PknG.

Significance

Mycobacterium tuberculosis(Mtb) protein kinase G (PknG), which is critical for Mtb intracellular survival, is a promising target for tuberculosis (TB) treatment. However, the molecular mechanisms underlying PknG-host interactions remain largely unclear. Here we demonstrate that PknG serves as both the ubiquitin-activating enzyme and the ubiquitin ligase to promote the ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-β-activated kinase 1 (TAK1), thus inhibiting NF-κB signaling activation. PknG promotes the attachment of ubiquitin to ubiquitin-conjugating enzyme UbcH7 via an isopeptide bond, instead of a usual thiol-ester bond, and releases the ubiquitin from UbcH7 by acting as an isopeptidase. These findings provide important information for rational development of TB treatment via targeting unconventional ubiquitinating activity of PknG.