bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgen abuse among gay and bisexual men
Authors: Griffiths Scott , Jotanovic Dejan , Austen Emma
Published: September 2021

Purpose of review

Androgen abuse is more prevalent among gay and bisexual (i.e. sexual minority) men than heterosexual men. We review recent research about androgen abuse in sexual minority men and provide relevant social, cultural, and historical contexts.

Recent findings

Androgen abuse among sexual minority men is shaped by the intersections of sexuality, desirability, masculinity, and race. Muscular male bodies are desired and – in erotic settings especially – prized as literal embodiments of masculinity. Racist stereotypes unjustly diminish the desirability and masculinity of sexual minority men who belong to racial minorities, especially those who are Asian or Black, and the higher rates of androgen abuse among these racial minorities may reflect a compensatory motivation for these diminishments. The historical context for sexual minority men – decades of subjugation alongside stereotypes of masculinity-compromising effeminacy – further complicate the intersections of sexuality with androgen abuse. Harm minimization efforts led by empathetic endocrinologists stand the best chance of achieving positive outcomes for sexual minority men who use androgens.

More dedicated research on androgen abuse among sexual minority men is needed as this population requires thoughtfully designed research that is incorporative – at a minimum – of the complexities of sexuality, desirability, masculinity, and race.
Predictors of gross motor function and activities of daily living in children with cerebral palsy
Authors: Tarfa Halima Bukar , Hassan Auwal Bello , Badaru Umaru Muhammad , Abdullahi Auwal
Published: September 2021

To determine the influence of selected impairment variables, spasticity, trunk control, upper limb function and selective motor control of the lower limb on gross motor function and activities of daily living in children with cerebral palsy (CP). Seventy children with CP, 40 boys and 30 girls, with age range between 11 and 156 months were recruited in this cross-sectional study. Data on spasticity, selective motor control of the lower limb, upper limb function and trunk control were assessed using modified Ashworth scale (MAS), selective motor control of the lower limb (SCALE), paediatric arm function test, trunk motor control assessment and GMFM88, respectively. Among all the variables assessed, only trunk control significantly predicted gross motor function (beta = 0.880; P < 0.001) and activities of daily living (beta = 0.550; P < 0.05). However, gross motor function and activities of daily living have significant (P < 0.05) negative correlations with spasticity, and positive correlations with selective motor control of the lower limb and trunk control. Trunk control is the most influencing factor on gross motor function and activities of daily living in children with CP. Therefore, achieving trunk control especially in those at GMFCS levels V and VI should be a priority during the rehabilitation of children with CP.
Expression Analysis of GD2 by Immunohistochemistry in Invasive Breast Carcinoma: Clinical and Pathologic Correlation
Authors: Zhong Elaine , Brogi Edi , D’Alfonso Timothy M. , Wen Hannah , Frosina Denise , Cheung Nai-Kong , Jungbluth Achim A. , Ross Dara S.
Published: September 2021

The glycosphingolipid disialoganglioside GD2 is a cell surface–associated antigen expressed on tumors of neuroectodermal origin that serves as a target of immunotherapy in select cancer types. Information about the expression of GD2 in breast cancer is limited. In the present study, we investigate the utility of GD2 as a potential biomarker for targeted treatment. The study cohort consists of 386 breast carcinomas of several histologic types. GD2 expression was assessed in both whole tumor sections and tissue microarrays with anti-GD2 3F8 monoclonal antibody immunohistochemistry and correlated with clinicopathologic features and survival outcomes. A total of 134 (35%) breast carcinomas were positive for GD2, with a median H-score of 100. 3F8 staining displayed granular and predominantly cytoplasmic or perinuclear patterns, which was confined to the neoplastic tissue in nearly all cases. GD2 positivity was significantly associated with tumor histologic type (P=0.0015), low grade (P<0.0001), estrogen receptor positivity (P<0.0001), low stage (P=0.0014), and multifocality (P=0.022). Event-free survival and overall survival of patients with GD2-positive and GD2-negative tumors were not significantly different. Our results support further assessment of GD2 using the 3F8 antibody as a predictive and prognostic biomarker in breast cancer.
Improving Low-Density Fat by Condensing Cellular and Collagen Content through a Mechanical Process: Basic Research and Clinical Applications
Authors: Zhu Huidong , Quan Yuping , Wang Jing , Jiang Shenglu , Lu Feng , Cai Junrong , Liao Yunjun
Published: September 2021

Background:

Large-volume fat grafting results in high absorption and complication rates. Low-density fat includes small numbers of viable cells and considerable oil, resulting in nodules and oil cysts. This study evaluated a strategy for large-volume fat grafting using a mechanical process to condense low-density fat and transplanting it with high-density fat.

Methods:

Low-density fat, defined as the upper half of centrifuged lipoaspirates, was emulsified by intersyringe shifting and centrifuged to obtain condensed low-density fat. Fresh condensed low-density fat was analyzed by counting cells in the stromal vascular fraction, and by electron scanning and Western blotting. The retention rate and histologic changes of the product were analyzed using a fat grafting model in nude mice. Transplantation with a combination of condensed low-density fat and high-density fat was tested in patients undergoing breast reconstruction and breast augmentation.

Results:

The condensed low-density fat derived from low-density fat contained a large number of stromal vascular fraction cells and collagens, comparable to that of high-density fat and much higher than in low-density fat and Coleman fat. Retention rates 12 weeks after transplantation were higher for condensed low-density fat (55.0 ± 7.5 percent) than for low-density fat (31.1 ± 5.7 percent) and Coleman fat (41.1 ± 6.8 percent), with condensed low-density fat having fewer oil cysts and lower macrophage infiltration. Patients grafted with combined condensed low-density fat and high-density fat showed good long-term volume retention.

Conclusions:

Using mechanical methods to condense low-density fat to a level comparable to that of high-density fat is a practical method of improving fat graft retention and avoiding severe complications. This new strategy may improve the quality of lipoaspirates for patients requiring large-volume augmentation.
USP15 Enhances the Proliferation, Migration, and Collagen Deposition of Hypertrophic Scar–Derived Fibroblasts by Deubiquitinating TGF-βR1 In Vitro
Authors: Tu Longxiang , Lin Zunwen , Huang Qin , Liu Dewu
Published: September 2021

Background:

Hypertrophic scar is a fibroproliferative disorder caused by skin injury. The incidence of hypertrophic scar following trauma or burns is 40 to 70 percent or 70 percent, respectively. It has been shown that transforming growth factor (TGF) β1/Smad signaling plays a crucial role in hypertrophic scar, and that USP15 can regulate the activity of TGFβ1/Smad signaling to affect the progression of the disease. However, the underlying mechanism of USP15 in hypertrophic scar remains unclear. The authors hypothesized that USP15 was up-regulated and enhanced the proliferation, migration, invasion, and collagen deposition of hypertrophic scar–derived fibroblasts by deubiquitinating TGF-β receptor I (TβRI) in vitro.

Methods:

Fibroblasts were isolated from human hypertrophic scars in vitro. The knockdown and overexpression of USP15 in hypertrophic scar–derived fibroblasts were performed using lentivirus infection. The effect of USP15 on hypertrophic scar–derived fibroblast proliferation, migration, and invasion, and the expression of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3, were detected by Cell Counting Kit-8, scratch, invasion, quantitative real-time polymerase chain reaction, and Western blot assays. The interaction between USP15 and TβRI was detected by co-immunoprecipitation and ubiquitination assays.

Results:

The authors demonstrated that USP15 knockdown significantly inhibited the proliferation, migration, and invasion of hypertrophic scar–derived fibroblasts in vitro and down-regulated the expression of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3; in addition, USP15 overexpression showed the opposite trends (p < 0.05). Co-immunoprecipitation and ubiquitination assays revealed that USP15 interacted with TβRI and deubiquitinated TβRI.

Conclusion:

USP15 enhances the proliferation, migration, invasion, and collagen deposition of hypertrophic scar–derived fibroblasts by deubiquitinating TβRI in vitro.
Robotic Inguinal Hernia Repair After Prostatectomy: How to Navigate Safely
Authors: Salas-Parra Ruben D. , Lima Diego L. , Pereira Xavier , Cavazzola Leandro T. , Sreeramoju Prashanth , Malcher Flavio
Published: September 2021

Introduction:

In recent decades, minimally invasive approaches have found their place in treating a specific subset of patients with inguinal hernias, predominantly those with recurrent or bilateral disease. Classically, prior history of urologic pelvic operations, such as prostatectomy, has been listed as relative contraindication for minimally invasive inguinal hernia repair. As the adoption of the robotics platform continues to grow, we aim to outline a feasible robotic-assisted inguinal hernia repair technique in patients with previous prostatectomies. We report the outcomes of 15 patients who underwent repair at 2 institutions.

Methods:

This is a retrospective case series of 15 patients who underwent robotic transabdominal preperitoneal approach repair of their inguinal hernias after prostatectomy. Demographics, intraoperative variables, and outcomes of our cases are described.

Results:

Fifteen patients were included in our cohort. All patients had a history of prostatectomy (7 open, 2 laparoscopic, and 6 robotic) due to prostate cancer. Median age was 70 years old (range: 60 to 89 y), with a median body mass index of 26.3 kg/m2 (range: 20.5 to 37.4 kg/m2). Hernia defects were bilateral in 6 patients and unilateral in the remaining 9 (right; 6, left; 3). The shortest interval between prostatectomy and subsequent hernia repair was 4 months (range: 4 to 216 mo). The median operative time was 139 min (range: 91 to 281 min). All defects were repaired using a polypropylene mesh except in 1 case, where a coated monofilament polyester mesh was used after having a large peritoneal defect to close, preventing future adhesions to the bowel. Mesh sizes used were large (16×11 cm), extra-large (17×12 cm) for anatomic mesh, and 20×15 cm for the monofilament polyester mesh. The mesh was fixed in 14 of 15 cases. Fixation was accomplished with absorbable suture (n=13), barbed suture (n=1), and fibrin sealant (n=1). Peritoneal closure was always performed using a continuous running v-loc suture. There were no documented major intraoperative complications, no 30-day readmission, or recurrences recorded within the follow-up period. Postoperatively, only 2 seromas and 1 hematoma were documented during the follow-up period.

Conclusions:

Robotic inguinal hernia repairs in patients with previous prostatectomy is safe and feasible in most patients. Larger patient series are needed to confirm these findings.
Radiocarbon signature reveals that most springtails depend on carbon from living plants
Authors: Fujii Saori , Haraguchi Takashi F. , Tayasu Ichiro
Published: September 2021

Terrestrial carbon cycling is largely mediated by soil food webs. Identifying the carbon source for soil animals has been desired to distinguish their roles in carbon cycling, but it is challenging for small invertebrates at low trophic levels because of methodological limitations. Here, we combined radiocarbon (14C) analysis with stable isotope analyses (13C and15N) to understand feeding habits of soil microarthropods, especially focusing on springtail (Collembola). Most Collembola species exhibited lower Δ14C values than litter regardless of theirδ13C andδ15N signatures, indicating their dependence on young carbon. In contrast with general patterns across all taxonomic groups, we found a significant negative correlation betweenδ15N and Δ14C values among the edaphic Collembola. This means that the species with higherδ15N values depend on C from more recent photosynthate, which suggests that soil-dwelling species generally feed on mycorrhizae to obtain root-derived C. Many predatory taxa exhibited higher Δ14C values than Collembola but lower than litter, indicating non-negligible effects of collembolan feeding habits on the soil food web. Our study demonstrated the usefulness of radiocarbon analysis, which can untangle the confounding factors that change collembolanδ15N values, clarify animal feeding habits and define the roles of organisms in soil food webs.
Estimating parameters of a stochastic cell invasion model with fluorescent cell cycle labelling using approximate Bayesian computation
Authors: Carr Michael J. , Simpson Matthew J. , Drovandi Christopher
Published: September 2021

We develop a parameter estimation method based on approximate Bayesian computation (ABC) for a stochastic cell invasion model using fluorescent cell cycle labelling with proliferation, migration and crowding effects. Previously, inference has been performed on a deterministic version of the model fitted to cell density data, and not all parameters were identifiable. Considering the stochastic model allows us to harness more features of experimental data, including cell trajectories and cell count data, which we show overcomes the parameter identifiability problem. We demonstrate that, while difficult to collect, cell trajectory data can provide more information about the parameters of the cell invasion model. To handle the intractability of the likelihood function of the stochastic model, we use an efficient ABC algorithm based on sequential Monte Carlo. Rcpp and MATLAB implementations of the simulation model and ABC algorithm used in this study are available at
https://github.com/michaelcarr-stats/FUCCI
.
Complete complementarity relations and their Lorentz invariance
Authors: Basso Marcos L. W. , Maziero Jonas
Published: September 2021

It is well known that entanglement under Lorentz boosts is highly dependent on the boost scenario in question. For single-particle states, a spin-momentum product state can be transformed into an entangled state. However, entanglement is just one of the aspects that completely characterizes a quantum system. The other two are known as the wave-particle duality. Although the entanglement entropy does not remain invariant under Lorentz boosts, and neither do the measures of predictability and coherence, we show here that these three measures taken together, in a complete complementarity relation (CCR), are Lorentz invariant. Peres
et al.
(Peres
et al.
2002
Phys. Rev. Lett.
88
, 230402. (
doi:10.1103/PhysRevLett.88.230402
)) realized that even though it is possible to formally define spin in any Lorentz frame, there is no relationship between the observable expectation values in different Lorentz frames. Analogously, one can, in principle, define complementary relations in any Lorentz frame, but there is no obvious transformation law relating complementary relations in different frames. However, our result shows that the CCRs have the same value in any Lorentz frame, i.e. there is a transformation law connecting the CCRs. In addition, we explore relativistic scenarios for single and two-particle states, which helps in understanding the exchange of different aspects of a quantum system under Lorentz boosts.
Modal analysis of a viscous fluid falling over a compliantwall
Authors: Samanta Arghya
Published: September 2021

We study the modal instability of a three-dimensional Newtonian viscous fluid falling over a compliant wall under the framework of coupled evolution equations for normal velocity and normal vorticity, respectively. The Chebyshev spectral collocation numerical technique is applied in exploring unstable modes for the three-dimensional disturbances. The unstable zones pertaining to surface mode, wall mode and shear mode reduce as long as the spanwise wavenumber amplifies and corroborates the stabilizing influence of spanwise wavenumber. However, the onset of instability for the wall mode decays as long as the capillary number amplifies and ensures the destabilizing influence of the capillary number. Furthermore, the critical Reynolds number corresponding to surface mode found in the long-wave zone shifts towards the finite wavelength zone with increasing spanwise wavenumber and confirms the extinction of long-wave instability. But the inertialess instability created due to the wall mode disappears with increasing spanwise wavenumber. Moreover, the shear mode emerges in the high Reynolds number zone and is stabilized in the presence of spanwise wavenumber. In addition, the analytical derivation of Squire’s theorem is provided in appendix B for the flow over a compliant wall.
Disseminated sporotrichosis in a person with human immunodeficiency virus disease
Authors: Tshisevhe Vhudzani , Skosana Lebogang , Motse Kagiso , Maphosa Tinashe , Mitton Barend
Published: September 2021

Introduction.Disseminated sporotrichosis is an incapacitating infection caused by the dimorphic fungusSporothrix schenckii. Because this condition may mimic the presentation of tuberculosis, syphilis and other bacterial infections, the diagnosis may be missed or delayed.

Case Presentation.We describe a case of disseminated sporotrichosis in a patient with poorly controlled human immunodeficiency virus infection. The patient was initially treated for bacterial skin infections. The differential diagnosis also included tuberculosis and syphilis. Only after appropriate specimens had been sent for microbiological and histopathological investigations was the diagnosis of disseminated sporotrichosis made and appropriate treatment started. The patient showed a good clinical response to itraconazole.

Conclusion.This report highlights the importance of having a high index of suspicion of endemic mycoses when managing immunocompromised patients. The report also demonstrates that a delay in the diagnosis of sporotrichosis increases morbidity and results in unnecessary and inappropriate treatment with associated costs and adverse effects.
Blautia intestinalis sp. nov., isolated from human feces
Authors: Wang Yu-Jing , Abdugheni Rashidin , Liu Chang , Zhou Nan , You Xin , Liu Shuang-Jiang
Published: September 2021

A strictly anaerobic bacterial strain (27-44T) was isolated from a stool specimen from an autistic child collected in PR China. The strain was Gram-stain-positive, non-motile, non-pigmented, non-spore-forming, and cells were oval to rod-shaped. Strain 27-44T grew at 20–40 °C (optimal at 37 °C) and at pH 6.0–10 (optimal at 6.0–8.0). The major polar lipids were one phospholipid, two glycolipids, two aminophospholipids and one unidentified lipid. The major cellular fatty acids of strain 27-44T were C16 : 0 and C17 : 0 2-OH. The end product of glucose fermentation was mainly butyric acid. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 27-44T was a member of the genus

Blautia

and phylogenetically closely related to

Blautia obeum

ATCC 29174T (with 97.8 % seque nce similarity). The genome of strain 27-44T was 3.5 Mbp with a DNA G+C content of 42.36 mol%. A total of 3436 genes were predicted and, of these, 3133 genes were annotated by KEGG. On the basis of phenotypic, chemotaxonomic and phylogenetic comparisons, strain 27-44T represents a novel species within the genus

Blautia

, for which the name Blautia intestinalis sp. nov. is proposed. The type strain is 27-44T= CGMCC 1.5285T=NBRC 113774T.
Evolution of COVID-19 mortality over time: results from the Swiss hospital surveillance system (CH-SUR)
Authors: Roelens Maroussia , Martin Alexis , Friker Brian , Sousa Filipe Maximiano , Thiabaud Amaury , Vidondo Beatriz , Buchter Valentin , Gardiol Céline , Vonlanthen Jasmin , Balmelli Carlo , Battegay Manuel , Berger Christoph , Buettcher Michael , Cusini Alexia , Flury Domenica , Heininger Ulrich , Niederer-Loher Anita , Riedel Thomas , Schreiber Peter W. , Sommerstein Rami , Troillet Nicolas , Tschudin-Sutter Sarah , Vetter Pauline , Bernhard-Stirnemann Sara , Corti Natascia , Gaudenz Roman , Marschall Jonas , Nussbaumer-Ochsner Yvonne , Senn Laurence , Vuichard-Gysin Danielle , Zimmermann Petra , Zucol Franziska , Iten Anne , Keiser Olivia ,   CH-SUR study group
Published: September 2021

Background

When comparing the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons, and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors.

Methods

We investigated the trends in COVID-19 related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to May 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk.

Results

Our analysis included 16,030 episodes recorded in CH-SUR, with 2,320 reported deaths due to COVID-19 (13.0% of included episodes). We found that overall in-hospital mortality was lower during the second wave of COVID-19 compared to the first wave (HR 0.71, 95% CI 0.69 – 0.72, p-value < 0.001), a decrease apparently not explained by changes in demographic characteristics of patients. In contrast, mortality in intermediate and intensive care significantly increased in the second wave compared to the first wave (HR 1.48, 95% CI 1.42 – 1.55, p-value < 0.001), with significant changes in the course of hospitalisation between the first and the second wave.

Conclusion

We found that, in Switzerland, COVID-19 mortality decreased among hospitalised persons, whereas it increased among patients admitted to intermediate or intensive care, when comparing the second wave to the first wave. We put our findings in perspective with changes over time in case management, treatment strategy, hospital burden and non-pharmaceutical interventions. Further analyses of the potential effect of virus variants and of vaccination on mortality would be crucial to have a complete overview of COVID-19 mortality trends throughout the different phases of the pandemic.
Dynamics of mask use as a prevention strategy against SARS-Cov-2 in Panama
Authors: Fernández-Marín Hermógenes , Bruner-Montero Gaspar , Portugal-Loayza Ana , Miranda Virginia , Villareal Alcibíades , Ortega Eduardo , Núñez-Samudio Virginia , Landires Iván , Mejia Luis C. , López-Vergès Sandra , Wcislo William T. , Jagannatha Rao K.S.
Published: September 2021

Background

Early in the SARS-CoV-2 pandemic, many national public health authorities implemented non-pharmaceutical interventions to mitigate disease outbreaks. Panamá established mandatory mask use two months after its first documented case. Initial compliance was high, but diverse masks were used in public areas. We studied behavioral dynamics of mask use through the first two COVID waves in Panama, to improve implementation of effective, low-cost public health containment measures, when populations are exposed to novel air-borne pathogens.

Methods

Mask use behavior was recorded from pedestrians in four Panamanian populations (August to December 2020). We recorded facial coverings; and if used, the type of mask, and gender and estimated age of the wearer.

Findings

People were highly compliant (> 95%) with mask mandates, and demonstrated important population-level behaviours: 1) decreasing use of cloth masks over time, and increasing use of surgical masks; 2) mask use was 3-fold lower in sub-urban neighborhoods than other public areas; and 3) young people were least likely to wear masks.

Interpretation

Results help focus highly-effective, low-cost, public health interventions for managing and controlling a pandemic. Considerations of behavioural preferences for different masks, relative to pricing and availability, are essential for optimizing public health policies. Policies to increase availability of effective masks, and behavioral nudges to increase acceptance, and to facilitate mask usage, during the on-going SARS-CoV-2 pandemic, and for future pandemics of respiratory pathogens, are key tools, especially for nations lagging in access to expensive vaccines and pharmacological approaches.

Funding

11-2020 SNI Grant, SENACYT.
High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-related Acute Respiratory Distress Syndrome: A Multicenter and Randomized Open-label Clinical Trial
Authors: Maskin Luis Patricio , Bonelli Ignacio , Olarte Gabriel Leonardo , Palizas Fernando , Velo Agostina E , Lurbet María Fernanda , Lovazzano Pablo , Kotsias Sophia , Attie Shiry , Saubidet Ignacio Lopez , Baredes Natalio D , Setten Mariano , Rodriguez Pablo Oscar
Published: September 2021

Purpose

To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome due to coronavirus disease 2019 (C-ARDS)

Materials

A multicenter randomized controlled trial in adults with C-ARDS. Patients received 16 mg/d of dexamethasone intravenously for five days followed by 8 mg/d of dexamethasone for five days, or 6 mg/d of dexamethasone intravenously for 10 days.

Results

Data from 98 patients who received at least one dose of dexamethasone were analyzed. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 d [interquartile range (IQR) 0–14 d] versus 0 d [IQR 0–1 d]; P=0.231). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P<0.001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms.

Conclusions

Among patients with C-ARDS, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator

Clinical Trial Registered: NCT04395105
Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus Lateralis Myosin Regulatory Light Chain Phosphorylation But Does Not Alter Markers of Bone Turnover: A Randomised Controlled Trial
Authors: O’Leary Mary F. , Jackman Sarah R. , Sabou Vlad R. , Campbell Matthew I , Tang Jonathan C. Y. , Dutton John , Bowtell Joanna L.
Published: September 2021

Background

Shatavari has long been used as an Ayurvedic herb for women’s health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor, and may therefore benefit postmenopausal women since postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis.

Methods

In a randomised double-blind trial, 20 postmenopausal women (68.5 ± 6 y) ingested either placebo (N=10) or shatavari (N=10; 1000 mg/d, equivalent to 26,500 mg/d fresh weight shatavari) for 6 weeks. Handgrip and knee extensor strength were measured at baseline and at 6 weeks. Vastus lateralis (VL) biopsy samples were obtained. Data are presented and analysed (t test/Mann Whitney U) as difference scores (Week 6 – baseline, median ± interquartile range).

Results

Handgrip, (but not knee extensor) strength was improved by shatavari supplementation (shatavari +0.7 ± 1.1 kg, placebo -0.4 ± 1.3 kg; p=0.04). Myosin regulatory light chain phosphorylation, a known marker of improved myosin contractile function, was increased in VL following shatavari supplementation (immunoblotting; placebo -0.08 ± 0.5 a.u. shatavari +0.3 ± 1 arbitrary units (a.u.); p=0.03). Shatavari increased phosphorylation of Aktser473 (Aktser473 (placebo -0.6 ± 0.6 a.u. shatavari +0.2 ± 1.3 a.u; p=0.03) in VL. Shatavari supplementation did not alter plasma markers of bone turnover (P1NP, β-CTX) and stimulation of human osteoblasts with pooled sera (N=8 per condition) from placebo and shatavari supplementation conditions did not alter cytokine or metabolic markers of osteoblast activity.

Conclusions

Shatavari may improve muscle function and contractility via myosin conformational change and warrants further investigation of its utility in conserving musculoskeletal function in postmenopausal women.

Trial Registration

Retrospectively registered at clinicaltrials.gov as NCT05025917 on 30/08/21.
Deleterious drugs in COVID-19: a rapid systematic review and meta-analysis
Authors: Holder Michael , Heeney Catherine , Malden Stephen , Perera Uditha , Sheikh Aziz
Published: September 2021

Background

Concerns have been expressed about a number of drugs that potentially worsen outcomes in patients with COVID-19. We sought to identify all potentially deleterious drug groups in COVID-19 and critically assess the underpinning strength of evidence pertaining to the harmful effects of these drugs.

Methods and findings

We performed a rapid systematic review, searching Medline, Embase and two COVID-19 portfolios (WHO COVID-19 database and NIH iSearch COVID-19 portfolio) for papers and preprints related to primary studies investigating drugs identified as potentially deleterious. Primary outcomes were direct measures of susceptibility to infection, disease severity and mortality. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tools. Random-effects meta-analyses were used for data synthesis with further subgroup analyses where possible for specific outcome, study design, statistical adjustment and drug groups when two were combined. Sensitivity analyses were performed by removing any studies at high risk of bias and by publication status.

49 observational studies (15 peer-reviewed papers and 34 preprints) reported primary outcomes for eight drug groups hypothesised to be deleterious. Meta-analysis showed that acute inpatient corticosteroid use was associated with increased mortality (OR 2.22, 95% CI 1.26-3.90), however this result appeared to have been biased by confounding via indication. One subgroup analysis indicated an association between immunosuppressant use and susceptibility to COVID-19 among case control and cross-sectional studies (OR 1.29, 95% CI 1.19-1.40) but this was not found with cohort studies (OR 1.11, 95% CI 0.86-1.43). Studies which adjusted for multiple confounders showed that people taking angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) required a lower level of care (OR 0.85, 95% CI 0.74-0.98). Furthermore, studies which combined these two drug groups in their analysis demonstrated an association with a lower mortality (OR 0.68, 95% CI 0.55-0.85).

Conclusions

We found minimal high quality or consistent evidence that any drug groups increase susceptibility, severity or mortality in COVID-19. Converse to initial hypotheses, we found some evidence that regular use of ACEIs and ARBs prior to infection may be effective in reducing the level of care required, such as requiring intensive care, in patients with COVID-19.
Nurse staffing levels and patient outcomes: a systematic review of longitudinal studies
Authors: Dall’Ora Chiara , Saville Christina , Rubbo Bruna , Turner Lesley Y , Jones Jeremy , Griffiths Peter
Published: September 2021

Background

The contribution of registered nurses (RN) towards safe patient care has been demonstrated by several studies. However, most of the evidence is cross-sectional, hence the inability to demonstrate that staffing levels precede patient outcomes. No reviews have summarised longitudinal studies considering nurse staffing and patient outcomes.

Objectives

To synthesise longitudinal studies focusing on associations between nurse staffing levels and patient outcomes.

Methods

Systematic review. We conducted our search in 2020 and updated it in July 2021. We searched Medline, CINAHL, Embase and the Cochrane Library. We used the ROBINS-I tool for assessing risk of bias. We reported results narratively grouped by outcome.

Results

28 papers were included. Most studies were either at serious (n=12) or critical (n=6) risk of bias, with 3 studies at low risk of bias. Studies were conducted in a variety of settings and populations. Notwithstanding the limitations, findings are consistent with an overall picture of a beneficial effect from higher RN staffing on preventing patient death. Studies with the greatest risk of bias were judged as most likely to underestimate the effect of higher RN staffing. The evidence is less clear for other patient outcomes, but estimates, though at moderate or serious risk of bias, indicate that higher RN staffing is likely to lead to better patient outcomes. Evidence about the contribution of other nursing staff groups and skill mix of the team is unclear.

Conclusion

There is a likely causal relationship between low RN staffing and harm to patients, although uncertainties remain regarding the magnitude of effect. To address these uncertainties, future studies should be conducted in more than one hospital and using standardised measures when reporting staffing levels.
A tetracycline antibiotic minocycline prevents early aging phenotypes in mice heterozygous for RP58
Authors: Tanaka Tomoko , Hirai Shinobu , Manabe Hiroyuki , Endo Kentaro , Nishito Yasumasa , Shimbo Hiroko , Yoshitane Hikari , Okado Haruo
Published: September 2021

In humans, cognitive and motor functions develop in association with maturation, followed by a decline in advancing age. In this study, we aimed to provide a method for extending healthy lifespan by preventing age-related phenomena. Therefore, we focused on RP58, a transcriptional repressor, whose expression is reduced during aging in the human cortex. In the Rp58 hetero-knockout (KO) mice, object location memory was impaired even at 4–5 months, while it was normal in the wild-type mice at 4–5 months but was impaired at 12–18 months. These results indicate an early onset of impaired spatial memory in the mutant mice. As the underlying mechanism, the Rp58 hetero-KO mice showed early onset of DNA damage accumulation and microglial activation in the dentate gyrus due to a DNA repair defect that is generally observed with aging. As another hallmark of aging, we focused on mitochondrial function and detected mitochondrial abnormalities in the Rp58 hetero-KO mice at 4–5 months. Notably, continuous treatments with minocycline, a neuroprotective and anti-inflammatory antibiotic, prevented the facilitation of age-related phenomena in the Rp58 hetero-KO mice. These results suggest the availability of the Rp58 hetero-KO mice as a novel mouse model of human-like early aging and provide a therapeutic strategy to prevent age-related phenomena using minocycline.

Highlight

Rp58 hetero-KO mice exhibit early aging phenotypes including impairment of spatial cognition

Rp58 hetero-KO mice show early accumulation of DNA damage due to a defect in the DNA repair system

Treatment with minocycline prevented cognitive dysfunction observed in Rp58 hetero-KO mice
Microbial induced calcite precipitation can consolidate martian and lunar regolith simulants
Authors: Dikshit Rashmi , Gupta Nitin , Dey Arjun , Viswanathan Koushik , Kumar Aloke
Published: September 2021

We demonstrate that Microbial Induced Calcite Precipitation (MICP) can be utilized for creation of consolidates of Martian Simulant Soil (MSS) and Lunar Simulant Soil (LSS) in the form of a ‘brick’. A urease producer bacteria, Sporosarcina pasteurii, was used to induce the MICP process for the both simulant soils. An admixture of guar gum as an organic polymer and NiCl2, as bio-catalyst to enhance urease activity, was introduced to increase the compressive strength of the biologically grown bricks. A casting method was utilized for a slurry consisting of the appropriate simulant soil and microbe; the slurry over a few days consolidated in the form of a ‘brick’ of the desired shape. In case of MSS, maximum strength of 3.3 MPa was obtained with 10mM NiCl2 and 1% guar gum supplementation whereas in case of LSS maximum strength of 5.65 MPa was obtained with 1% guar gum supplementation and 10mM NiCl2. MICP mediated consolidation of the simulant soil was confirmed with field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD). Our work demonstrates a biological approach with an explicit casting method towards manufacturing of consolidated structures using extra-terrestrial regolith simulant; this is a promising route for in situ development of structural elements on the extra-terrestrial habitats.
A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
Authors: Feng Canran , Torimaru Kyosuke , Lim Mandy Yu Theng , Chak Li-Ling , Shiimori Masami , Tsuji Kosuke , Tanaka Tetsuya , Iida Junko , Okamura Katsutomo
Published: September 2021

Small regulatory RNAs (sRNAs) are involved in antiviral defense and gene regulation. Although roles of RNA-dependent RNA Polymerases (RdRPs) in sRNA biology are extensively studied in nematodes, plants and fungi, understanding of RdRP homologs in other animals is still lacking. Here, we study sRNAs in the ISE6 cell line, which is derived from the black-legged tick, an important vector of human and animal pathogens. We find abundant classes of ∼22nt sRNAs that require specific combinations of RdRPs and sRNA effector proteins (Argonautes or AGOs). RdRP-dependent sRNAs possess 5’- monophosphates and are mainly derived from RNA polymerase III-transcribed genes and repetitive elements. Knockdown of RdRPs misregulates genes including RNAi-related genes and the regulator of immune response Dsor1. Sensor assays demonstrate that Dsor1 is downregulated by RdRP through the 3’UTR that contains a target site of RdRP-dependent repeat-derived sRNAs. Consistent with viral gene repression by the RNAi mechanism using virus-derived small interfering RNAs, viral transcripts are upregulated by AGO knockdown. On the other hand, RdRP knockdown unexpectedly results in downregulation of viral transcripts. This effect is dependent on Dsor1, suggesting that antiviral immunity is enhanced by RdRP knockdown through Dsor1 upregulation. We propose that tick sRNA pathways control multiple aspects of immune response via RNAi and regulation of signaling pathways.

Author summary

RNA-dependent RNA Polymerases (RdRPs) are essential for biogenesis of small regulatory RNAs (sRNAs) in many organisms such as plants and fungi, but its general importance in animals besides nematodes remains controversial because experimental evidence is lacking. By using a tick cell line, we demonstrate that RdRP-dependent sRNAs are abundantly expressed and tick RdRPs regulate gene expression. These results indicate that ticks have unexpectedly complex sRNA biogenesis pathways that are essential for proper gene regulation. Interestingly, we show that RdRP negatively regulates immune response by changing expression of a gene that is essential in an immunity-related signaling pathway. Because ticks are important vectors of human and animal pathogens, studying the novel tick sRNA pathways and their effects on immune signaling may lead to a better understanding of vector-virus interactions.
pcnaDeep: A Fast and Robust Single-Cell Tracking Method Using Deep-Learning Mediated Cell Cycle Profiling
Authors: Gui Yifan , Xie Shuangshuang , Wang Yanan , Wang Ping , Yao Renzhi , Gao Xukai , Dong Yutian , Wang Gaoang , Chan Kuan Yoow
Published: September 2021

Motivation

Computational methods that track single-cells and quantify fluorescent biosensors in time-lapse microscopy images have revolutionised our approach in studying the molecular control of cellular decisions. One barrier that limits the adoption of single-cell analysis in biomedical research is the lack of efficient methods to robustly track single-cells over cell division events.

Results

Here, we developed an application that automatically tracks and assigns mother-daughter relationships of single-cells. By incorporating cell cycle information from a well-established fluorescent cell cycle reporter, we associate mitosis relationships enabling high fidelity long-term single-cell tracking. This was achieved by integrating a deep-learning based fluorescent PCNA signal instance segmentation module with a cell tracking and cell cycle resolving pipeline. The application offers a user-friendly interface and extensible APIs for customized cell cycle analysis and manual correction for various imaging configurations.

Availability and Implementation

pcnaDeep is an open-source Python application under the Apache 2.0 licence. The source code, documentation and tutorials are available at https://github.com/chan-labsite/PCNAdeep.

Supplementary Information

Supplementary data are available online.
Chronic hM4Di-DREADD mediated chemogenetic inhibition of forebrain excitatory neurons in postnatal or juvenile life does not alter adult mood-related behavior
Authors: Tiwari Praachi , Kapri Darshana , Pradhan Amartya , Balakrishnan Angarika , Chaudhari Pratik R. , Vaidya Vidita A.
Published: September 2021

G-protein coupled receptors (GPCRs) coupled to Gi-signaling, in particular downstream of monoaminergic neurotransmission, are posited to play a key role during developmental epochs (postnatal and juvenile), in shaping the emergence of adult anxio-depressive behaviors and sensorimotor gating. To address the role of Gi-signaling in these developmental windows, we used a CamKIIα-tTA::TRE hM4Di bigenic mouse line to express the hM4Di-DREADD in forebrain excitatory neurons and enhanced Gi-signaling via chronic administration of the DREADD agonist, CNO in the postnatal (PNCNO: postnatal day 2-14) or juvenile (JCNO: postnatal day 28-40) window. We confirmed that the expression of the HA-tagged hM4Di-DREADD was restricted to CamKII-positive neurons in the forebrain, and administration of CNO in postnatal or juvenile windows evoked inhibition in forebrain circuits of the hippocampus and cortex, as indicated by a decline in expression of the neuronal activity marker, c-fos. hM4Di-DREADD mediated inhibition of CamKIIα-positive forebrain excitatory neurons in postnatal or juvenile life did not impact the weight profile of mouse pups, and also did not influence the normal ontogeny of sensory reflexes. Further, postnatal or juvenile hM4Di-DREADD mediated inhibition of CamKIIα-positive forebrain excitatory neurons did not alter anxiety or despair-like behaviors in adulthood, and did not impact sensorimotor gating. Collectively, these results indicate that chemogenetic induction of Gi-signaling in CamKIIα-positive forebrain excitatory neurons in postnatal and juvenile temporal windows does not appear to impinge on the programming of anxio-depressive behaviors in adulthood.
Genome wide profiling of histone H3 lysine 4 methylation during the Chlamydomonas cell cycle reveals stable and dynamic properties of lysine 4 trimethylation at gene promoters and near ubiquitous lysine 4 monomethylation
Authors: Strenkert Daniela , Yildirim Asli , Yan Juying , Yoshinaga Yuko , Pellegrini Matteo , O’Malley Ronan C. , Merchant Sabeeha S. , Umen James G.
Published: September 2021

Chromatin modifications are key epigenetic regulatory features with roles in various cellular events, yet histone mark identification, gene wide distribution and relationship to gene expression remains understudied in green algae. Histone lysine methylation is regarded as an active chromatin mark in many organisms, and is implicated in mediating active euchromatin. We interrogated the genome wide distribution pattern of mono- and trimethylated H3K4 using Chromatin-Immunoprecipitation followed by deep-sequencing (ChIP-Seq) during key phases of the Chlamydomonas cell cycle: early G1 phase (ZT1) when cells initiate biomass accumulation, S/M phase (ZT13) when cells are undergoing DNA replication and mitosis, and late G0 phase (ZT23) when they are quiescent. Tri-methylated H3K4 was predominantly enriched at TSSs of the majority of protein coding genes (85%). The likelihood of a gene being marked by H3K4me3 correlated with it being transcribed at one or more time points during the cell cycle but not necessarily by continuous active transcription. This finding even applied to early zygotic genes whose expression may be dormant for hundreds or thousands of generations between sexual cycles; but core meiotic genes were completely missing H3K4me3 peaks at their TSS. In addition, bi-directional promoters regulating expression of replication dependent histone genes, had transient H3K4me3 peaks that were present only during S/M phase when their expression peaked. In agreement with biochemical studies, mono-methylated H3K4 was the default state for the vast majority of histones that were outside of TSS and terminator regions of genes. A small fraction of the genome which was depleted of any H3 lysine methylation was enriched for DNA cytosine methylation and the genes within these DNA methylation islands were poorly expressed. Genome wide H3K4me3 ChIP-Seq data will be a valuable resource, facilitating gene structural annotation, as exemplified by our validation of hundreds of long non-coding RNA genes.
Different DGAT1s show different TAG synthesis abilities and a specific amino acid substitution enhances oil accumulation
Authors: Hatanaka Tomoko , Tomita Yoshiki , Matsuoka Daisuke , Sasayama Daisuke , Fukayama Hiroshi , Azuma Tetsushi , Soltani Gishini Mohammad Fazel , Hildebrand David
Published: September 2021

Triacylglycerols (TAGs) are the major component of plant storage lipids. Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the final step of the Kennedy pathway, and responsible for plant oil accumulation. We previously found DGAT activity of Vernonia galamensis DGAT1 was distinctively higher than that of Arabidopsis thaliana DGAT1 and soybean DGAT1 in a yeast microsome assay. In this study, the DGAT1 cDNAs of Arabidopsis, Vernonia, soybean, and castor were introduced into Arabidopsis (ecotype Col-0). All Vernonia DGAT1 expressing lines showed a significantly higher oil content (average 49% relative increase compared to the wild type) followed by soybean, and castor. Most Arabidopsis DGAT1 over-expressing lines did not show a significant increase. In addition to these four DGAT1s, sunflower, Jatropha and sesame DGAT1 genes were introduced into the TAG biosynthesis defective yeast mutant (H1246). In the yeast expression culture, DGAT1s from Arabidopsis, castor, and soybean only slightly increased TAG content, however, DGAT1s from Vernonia, sunflower, Jatropha, and sesame remarkably increased TAG content more than 10 times higher than the former three DGAT1s. Three amino acid residues were characteristically common in the latter four DGAT1s. Using soybean DGAT1, these amino acid substitutions by site-directed mutagenesis was performed and analyzed. These substitutions substantially increased the TAG content.

Highlight

DGAT1s from several plant species were tested their TAG accumulation promotion in Arabidopsis and yeast. They were divided into high and low function and single amino acid substitution enhanced function