bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and Facilitators to Adolescent and Young Adult Cancer Trial Enrollment: NCORP Site Perspectives
Authors: Siembida Elizabeth J , Loomans-Kropp Holli A , Tami-Maury Irene , Freyer David R , Sung Lillian , Crosswell Howland E , Pollock Brad H , Roth Michael E
Published: March 2021

Background

Although it is well documented that adolescents and young adults (AYAs) with cancer have low participation in cancer clinical trials (CCTs), the underlying reasons are not well understood. We used the National Cancer Institute Community Oncology Research Program (NCORP) network to identify barriers and facilitators to AYA CCT enrollment, and strategies to improve enrollment at community-based and minority and/or underserved sites.

Methods

We performed one-on-one semistructured qualitative interviews with stakeholders (NCORP site principle investigators, NCORP administrators, physicians involved in enrollment, lead clinical research associates or clinical research nurses, nurse navigators, regulatory research associates, patient advocates) in the AYA CCT enrollment process. NCORP sites that included high and low AYA–enrolling affiliate sites and were diverse in geography and department representation (eg, pediatrics, medical oncology) were invited to participate. All interviews were recorded and transcribed. Themes related to barriers and facilitators and strategies to improve enrollment were identified.

Results

We conducted 43 interviews across 10 NCORP sites. Eleven barriers and 13 facilitators to AYA enrollment were identified. Main barriers included perceived limited trial availability and eligibility, physician gatekeeping, lack of provider and research staff time, and financial constraints. Main facilitators and strategies to improve AYA enrollment included having a patient screening process, physician endorsement of trials, an “AYA champion” on site, and strong communication between medical and pediatric oncology.

Conclusions

Stakeholders identified several opportunities to address barriers contributing to low AYA CCT enrollment at community-based and minority and/or underserved sites. Results of this study will inform development and implementation of targeted interventions to increase AYA CCT enrollment.
Vibration of rotating circular cylindrical shells with distributed springs
Authors: Yang Fuchun , Jiang Xiaofeng , Du Fuxin
Published: March 2021

Free vibrations of rotating cylindrical shells with distributed springs were studied. Based on the Flügge shell theory, the governing equations of rotating cylindrical shells with distributed springs were derived under typical boundary conditions. Multicomponent modal functions were used to satisfy the distributed springs around the circumference. The natural responses were analyzed using the Galerkin method. The effects of parameters, rotation speed, stiffness, and ratios of thickness/radius and length/radius, on natural response were also examined.
The hepatoprotective effect of silibinin after hepatic ischemia/reperfusion in a rat model is confirmed by immunohistochemistry and qRT-PCR
Authors: Betsou Afrodite , Lambropoulou Maria , Georgakopoulou Anastasia-Eirini , Kostomitsopoulos Nikolaos , Konstandi Ourania , Anagnostopoulos Konstantinos , Tsalikidis Christos , Simopoulos Constantinos E , Valsami Georgia , Tsaroucha Alexandra K
Published: March 2021

Objectives

We investigated the positive effect of silibinin after IV administration as silibinin-hydroxypropyl-β-cyclodextrin lyophilized product, by measuring gene expression and liver tissue protein levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, matrix metalloproteinases matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases-2.

Methods

63 Wistar rats of age 13.24±4.40 weeks underwent ischemia/reperfusion (I/R) injury of the liver. The animals were randomized into three groups: Sham (S; n = 7); Control (C; n-28); silibinin (Si; n-28). The C and Si groups underwent 45 min ischemia. Si received silibinin-hydroxypropyl-β-cyclodextrin intravenously immediately before reperfusion at a dose of 5 mg/kg. Both groups were further divided into 4 subgroups, based on euthanasia time (i.e., 60, 120, 180 and 240 min).

Key findings

qRT-PCR results confirmed the statistically significant reduction of the expression of the pro-inflammatory factors at 240 min after I/R injury (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) and the increase of tissue inhibitor of matrix metalloproteinases-2 in liver tissue in the Si group. Moreover, results of immunohistochemistry levels confirmed that at 240 min pro-inflammatory factors (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases ( matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) had a statistically significantly lower expression in the Si group while tissue inhibitor of matrix metalloproteinases-2 had a higher expression.

Conclusions

Silibinin may have a beneficial effect on the protection of the liver.
Induction of somatic mutations by low concentrations of tritiated water (HTO): evidence for the possible existence of a dose-rate threshold
Authors: Nagashima Haruki , Hayashi Yuki , Sakamoto Yuki , Komatsu Kenshi , Tauchi Hiroshi
Published: March 2021

Tritium is a low energy beta emitter and is discharged into the aquatic environment primarily in the form of tritiated water (HTO) from nuclear power plants or from nuclear fuel reprocessing plants. Although the biological effects of HTO exposures at significant doses or dose rates have been extensively studied, there are few reports concerning the biological effects of HTO exposures at very low dose rates. In the present study using a hyper-sensitive assay system, we investigated the dose rate effect of HTO on the induction of mutations. Confluent cell populations were exposed to HTO for a total dose of 0.2 Gy at dose rates between 4.9 mGy/day and 192 mGy/day by incubating cells in medium containing HTO. HTO-induced mutant frequencies and mutation spectra were then investigated. A significant inflection point for both the mutant frequency and mutation spectra was found between 11 mGy/day and 21.6 mGy/day. Mutation spectra analysis revealed that a mechanistic change in the nature of the mutation events occurred around 11 mGy/day. The present observations and published experimental results from oral administrations of HTO to mice suggest that a threshold dose-rate for HTO exposures might exist between 11 mGy/day and 21.6 mGy/day where the nature of the mutation events induced by HTO becomes similar to those seen in spontaneous events.
Health effects triggered by tritium: how do we get public understanding based on scientifically supported evidence?
Authors: Matsumoto Hideki , Shimada Yoshiya , Nakamura Asako J , Usami Noriko , Ojima Mitsuaki , Kakinuma Shizuko , Shimada Mikio , Sunaoshi Masaaki , Hirayama Ryoichi , Tauchi Hiroshi
Published: March 2021

The Commission for ‘Corresponding to Radiation Disaster of the Japanese Radiation Research Society’ formulated a description of potential health effects triggered by tritium. This was in response to the issue of discharging water containing tritium filtered by the Advanced Liquid Processing System (ALPS), generated and stored in Fukushima Daiichi Nuclear Power Station after the accident. In this review article, the contents of the description, originally provided in Japanese, which gives clear and detailed explanation about potential health effects triggered by tritium based on reliable scientific evidence in an understandable way for the public, were summarized. Then, additional information about biochemical or environmental behavior of organically bound tritium (OBT) were summarized in order to help scientists who communicate with general public.
Acute pancreatitis as a late complication of intra-gastric balloon insertion
Authors: Abdulghaffar Shareefa , Badrawi Noor , Gowda Swaroop Keshe , AlBastaki Usama , AlNuaimi Dana
Published: March 2021

Intra-gastric balloon (IGB) insertion is a safe, well-tolerated and an effective weight loss procedure. It is commonly used as a step prior to bariatric surgery in obese patients with co-morbidities and failed conservative weight-loss methods. The main side effects post-IGB placement include nausea, vomiting and abdominal pain. The reported complications of IGB include balloon over-inflation, balloon migration, esophagitis, ulceration, gastric perforation and bowel obstruction. We report a case of acute pancreatitis attributed to IGB placement, which is a rare complication of this procedure. The diagnosis of acute pancreatitis due to IGB was made after excluding other causes of acute pancreatitis by radiological imaging. The patient underwent endoscopic IGB removal with rapid post-surgical improvement of her clinical course.
Legal tools for addressing uncertainty and managing risks in the energy sector: is there a role for international disaster law?
Authors: Antoine Ibrahim Imad
Published: March 2021

The Covid-19 pandemic has highlighted once again the existing legal vacuums in the energy sector when it comes to addressing various situations such as disaster risk management and reduction. This reality can be seen in various instances where other regulatory frameworks are used instead of energy law. This article seeks to address the existing legal vacuum in the energy field in the context of pre- and post-energy disasters, such as the Covid-19 health disaster resulting in negative consequences for the energy sector. The author argues that international disaster law, taking the Sendai Framework for Disaster Risk Reduction as a case study, can provide guidance when it comes to managing pre- and post-energy disasters scenarios. The author will support this claim by examining the potential use of the Sendai Framework priorities as guidance for policymakers in addressing disasters in the energy field while stressing the need to strike a balance between using existing binding and nonbinding frameworks from other regulatory fields to address the legal gaps and making sure that energy law applies in such situations.
Insight into skywave theory and breakthrough applications in resource exploration
Authors: Di Qingyun , Fu Changmin , Xue Guoqiang , Wang Miaoyue , An Zhiguo , Wang Ruo , Wang Zhongxing , Lei Da , Zhuo Xianjun
Published: March 2021

Skywave refers to the electromagnetic wave reflected or refracted from the ionosphere and propagated in the form of a guided wave between the ionosphere and the Earth's surface. Since the skywave can propagate over large distances, it has been widely used in long-distance communication. This paper explores and demonstrates the feasibility of skywave for deep resource and energy exploration at depths of up to 10 km. Theoretical and technical advancements were accomplished in furthering skywave applications. A new solution method based on Green's function has been developed to study skywave propagation in a fully coupled lithosphere-air-ionosphere full space model. For the first time, the model allows one to study skywave distribution characteristics in the lithosphere containing inhomogeneity such as ore deposits or oil and gas reservoirs. This model also lays a foundation for skywave data processing and interpretation. On a parallel line, we have developed a multi-channel, broadband, low-noise, portable data acquisition system suitable for receiving skywave signals. Using the skywave field excited by a high-power fixed source located in central China, actual field surveys have been carried out in some areas in China including the Biyang depression of Henan Province. The initial results appear encouraging—the interpreted resistivity models prove to be consistent with those of seismic exploration and known geological information, and the exploration cost is only ∼1/4 to 1/10 that of seismic surveys. These initial successful applications of the skywave theory lay a solid foundation for further verification of the new method.
Helping
Authors: Ungemah Joe
Published: March 2021

This chapter investigates why people will help in some circumstances and fail to act in others. The brutal murder of Kitty Genovese in 1964 was witnessed by 37 witnesses, yet no one intervened, kick-starting research into understanding what elements of the social context causes paralysis in people to act. This is compared to a 2015 accident in London, which saw 50 bystanders lift a bus off a cyclist. The chapter unearths the rules of helping behavior and how to overcome the diffusion of responsibility. When the need for help is apparent, interpreted correctly, and responsibility to act is clear, the chances to overcome paralysis is high. Taking advantage of these rules is especially important for the gig economy, where the connections between people are more tenuous and diffused across organizations.
Understanding Societal Resilience
Authors: Anholt Rosanne , van Dullemen Caroline , de Carvalho Juliana Santos , Rijbroek Joris , Sieckelinck Stijn , Slootman Marieke W.
Published: March 2021

Societal resilience is an emerging paradigm. It refers to responses and strategies at the level of individuals, groups, organizations, and societies that are dealing with complex societal problems. At the same time, these responses contribute to innovative solutions that make society more resilient to current and future challenges. Societal resilience is, however, conceptually relatively undefined. This ambiguity is generally seen as problematic for scholarly work. In this chapter, the authors show that societal resilience is an important social concept because of its openness. To study resilience requires research methodologies that engage many actual stakeholders. Collaborating with societal stakeholders allows not only for co-generating knowledge of local relevance, but also stimulating a comprehensive and critical research approach. Therefore, the current openness of societal resilience does not constitute an undesirable theory gap. It enables the possibility of having plural perspectives based on the complex realities on the ground.
Berkeley and Malebranche on Human Freedom
Authors: Daniel Stephen H.
Published: March 2021

For Berkeley, I am not a substance who just happens to associate ideas; rather, I am the differentiation and association of those ideas, the will that there be such an order, variety, and comprehension. In creating minds, God creates an infinity of active principles in terms of which objects are intentionally identified in virtue of actions for which we are justifiably held responsible. As Malebranche suggests, God impels us toward the good in general, but we fixate on particular goods. For both thinkers, we need to see how things exhibit God’s grandeur in being related in infinite ways. In this way, we are freed to identify all things as purposive and harmonious.
Free for All
Authors: Case George
Published: March 2021

With bands like Grand Funk Railroad, Bachman-Turner Overdrive, Aerosmith, Ted Nugent, and Alice Cooper plying their trade around the stadiums and arenas of midwestern America, it was clear that a new clientele for rock ‘n’ roll had appeared and become viable. Who were the fans of these artists, and what were they getting from the music? How did the music industry cater to these fans among the populations of the heartland and the mill towns? In what ways were the musicians connecting with their public? And why did the players mean so much more to the punters than to the critics?
Eighteenth-Century Women’s Poetry and the Feminine Accomplishment
Authors: Keown Kathleen
Published: March 2021

This essay posits that the production and reception of eighteenth-century women’s poetry was shaped by a pervasive cultural paradigm: the concept of the ‘feminine accomplishment’. As the aspirational middling sort began to demarcate certain pastimes as signifiers of polite femininity, poetry was increasingly promoted alongside dancing, drawing, and singing as a genteel accomplishment for young women. However, this association was never secure: poetry always occupied an ambiguous position within accomplishment discourse, and the implications of its inclusion (or exclusion) were regularly contested. In the first investigation of this phenomenon, this essay draws upon early eighteenth-century conduct literature and biographical accounts to explore how women’s poetry was encouraged by some as an intellectually stimulating recreation (and a source of familial and national pride)—but was disparaged by others as a pretentious, frivolous, and potentially dangerous ornamentation. The experiences of women writers including Jane Brereton, Laetitia Pilkington, and Martha Fowke reveal that, although an aura of accomplished amateurism could authorize their poetic production (in both manuscript and print), it could also lead to their compositions being patronized and dismissed. The liminal nature of poetry’s ‘accomplished’ status would make women’s verse composition a locus for broader contemporary debates surrounding gender, class, education, and the professionalization of writing.
Effects of red macroalgae Asparagopsis taxiformis supplementation on the shelf life of fresh whole muscle beef
Authors: Bolkenov Bakytzhan , Duarte Toni , Yang Linghuan , Yang Frederick , Roque Breanna , Kebreab Ermias , Yang Xiang
Published: March 2021

This study was conducted to evaluate the effect of red macroalgae Asparagopsis taxiformis supplementation for cattle on the shelf life of fresh beef steaks (longissimus dorsi). Three treatment groups (seven steers per treatment) included: 1) Control diet, 2) Control diet + 0.25% of macroalgae inclusion (low dose, LD), and 3) Control + 0.5% of macroalgae inclusion (high dose, HD). After the animals were harvested, the strip loins from all animals were collected and aged for 14 days at the meat lab of the University of California, Davis. Then the strip loins were cut into steaks, packaged, and placed on a retail display case for 6 days. During a retail display, instrumental color (L*, a*, and b*) of lean muscle and external fat surfaces were measured every 12 h. Bacterial counts for total aerobic mesophilic bacteria (AMB), aerobic psychrotrophic bacteria (APB), and lactic acid bacteria (LAB) were assessed on days 0, 3, and 6 of retail display. The thiobarbituric acid reactive substances (TBARS) analysis was conducted to measure the lipid oxidation and the pH was also assessed on days 0, 3, and 6. No interactive effect between treatments and time on the shelf life of steaks was observed. The HD red macroalgae supplement decreased (P < 0.05) the lightness (L*) of the surface muscle of the steaks, while the lightness of the external fat was not affected (P < 0.05) by treatments throughout the retail display. The external fat yellowness of the steaks was lower (P < 0.05) in LD and HD treatment groups compared with the control group. An increase (P < 0.05) in counts of AMB, APB, and LAB was observed on the steaks from the steers in the HD treatment group while steaks in Control and LD group had similar bacterial numbers throughout the retail display. The results indicated that the shelf life of steaks from cattle in LD group remained the same as that of the Control group, but the HD of A. taxiformis caused a darker color of steaks with higher microbial counts, which may lead to a shortened shelf life due to undesirable appearance and faster microbial spoilage.
Understanding stigma and food inequity: a conceptual framework to inform research, intervention, and policy
Authors: Earnshaw Valerie A , Karpyn Allison
Published: March 2021

There is increasing understanding that stigma associated with poverty, race, nationality, gender, obesity, and other intersecting, socially devalued characteristics is a key social determinant of health that plays a role in food inequities; yet, the processes linking stigma with food inequities are poorly defined. Building on prior conceptual and empirical stigma research in public health, this paper introduces The Stigma and Food Inequity Framework. Supporting empirical evidence for the associations proposed by the framework is reviewed. The framework proposes that stigma is manifested at the structural (e.g., neighborhood infrastructure and targeted marketing) and individual (e.g., internalized stigma and stereotypes) levels. These stigma manifestations are associated with food inequities via a series of mediating mechanisms, including access to resources, the home food environment, and psychosocial and behavioral processes, which ultimately undermine healthy food consumption, contribute to food insecurity, and impact diet quality. The framework further proposes that processes linking stigma with food inequities are situated within contexts of history, culture, and human development. Future directions to address stigma and enhance food equity include the value of addressing the broad range of underlying structural stigma manifestations when creating policy to promote food equity.
Effect of tailoring on weight loss among young adults receiving digital interventions: an 18 month randomized controlled trial
Authors: Napolitano Melissa A , Whiteley Jessica A , Mavredes Meghan , Tjaden Ashley Hogan , Simmens Samuel , Hayman Laura L , Faro Jamie , Winston Ginger , Malin Steven , DiPietro Loretta
Published: March 2021

Weight loss outcomes among young adults in technology-based programs have been equivocal. The purpose of this study was to deliver digital weight loss treatments to young adults and examine the 6, 12, and 18 month effects on weight loss. Young adults with overweight/obesity (N = 459; 23.3 ± 4.4 years) were recruited from two university sites and randomly assigned to receive through Facebook and text messaging either personalized (TAILORED; n = 150) or generic (TARGETED; n = 152) weight loss information, messages, and feedback or general healthy body content (e.g., body image, sleep; CONTROL; n = 157). The study was powered to detect a 2.1-kg difference at all time points with the primary outcome being 18 months. There was no overall effect of treatment group on 6, 12, or 18 month weight loss (ps = NS). However, at 6 months, those in TAILORED who were highly engaged (completing >66%) lost more weight compared to CONTROL (−2.32 kg [95% confidence intervals: −3.90, −0.74]; p = .004), with the trend continuing at 12 months. A significant baseline body mass index (BMI) by treatment group interaction (p = .004) was observed at 6 months. Among participants in the lowest baseline BMI category (25–27.5 kg/m2), those in TAILORED lost 2.27 kg (−3.86, −0.68) more, and those in TARGETED lost 1.72 kg (−3.16, −0.29) more than CONTROL after adjusting for covariates. Among participants with a BMI between 27.5 and 30 kg/m2, those in TAILORED lost 2.20 kg (−3.90, −0.51) more than participants in TARGETED. Results did not persist over time with no treatment interaction at 12 or 18 months. Initial body weight should be considered when recommending weight loss treatments for young adults. More intensive interventions or stepped care approaches may be needed for young adults with obesity.
Allopurinol Protects Against Cholestatic Liver Injury in Mice Not Through Depletion of Uric Acid
Authors: Liu Jing , Fan Yang , Yu Hang , Xu Tong , Zhang Chunze , Zhou Lijun , Li Gentao , Zhang Youcai
Published: March 2021

Cholestasis is one of the most severe manifestations of liver injury and has limited therapeutic options. Allopurinol (AP), an inhibitor of uric acid (UA) synthesis, was reported to prevent liver damage in several liver diseases. However, whether AP protects against intrahepatic cholestatic liver injury and what is the role of UA in the pathogenesis of cholestasis remain unknown. In this study, we reported that AP attenuated liver injury in a mouse model of intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). AP showed no significant effect on glutathione depletion, inflammation, or bile acid metabolism in livers of ANIT-treated mice. Instead, AP significantly improved fatty acid β-oxidation in livers of ANIT-treated mice, which was associated with activation of PPARα. The protective effect of AP on cholestatic liver injury was not attributable to the depletion of UA, because both exogenous and endogenous UA prevented liver injury in ANIT-treated mice via inhibition of NF-kB-mediated inflammation. In conclusion, the present study provides a new perspective for the therapeutic use of AP and the role of UA in cholestatic liver injury.
Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria
Authors: Chijioke-Nwauche Ifeyinwa , Oguike Mary C , Nwauche Chijioke A , Beshir Khalid B , Sutherland Colin J
Published: March 2021

Background

In Nigeria, indiscriminate use of antimalarial drugs may contribute to the threat of drug resistance, but this has not been evaluated among people living with human immunodeficiency virus (HIV).

Methods

HIV-positive adults attending a university hospital HIV clinic and HIV-negative adult volunteers from the university hospital community with a positive blood film were treated with artemether–lumefantrine. Parasite DNA from before and after treatment was polymerase chain reaction amplified to identify molecular markers of drug susceptibility.

Results

The pfcrt76T genotype was prevalent among both HIV-positive and HIV-negative participants (78.6% and 68.2%, respectively). Three new mutations in the pfmdr1 gene—F73S, S97L and G165R—and the uncommon pfdhps S436F variant were detected, whereas pfdhps K540E and pfdhfr I164L were absent. The A437G allele of pfdhps predominated (62/66 [94%]). The I431 V mutation was found in 19 of 66 pretreatment pfdhps sequences (28.8%). The pfmdr1 86N allele was significantly more common at day 3 post-treatment than at baseline (odds ratio 8.77 [95% confidence interval 1.21 to 380]).

Conclusions

We found evidence of continued chloroquine use among HIV-positive individuals. Selection for the pfmdr1 86N after artemether–lumefantrine treatment was observed, indicating a possible threat to antimalarial efficacy in the study area. The complexity of pfdhps haplotypes emphasises the need for careful monitoring of anti-folate susceptibility in Nigeria.
Hormone therapy as a possible solution for postmenopausal women with nocturia: results of a pilot trial
Authors: Pauwaert Kim , Goessaert An-Sofie , Ghijselings Lynn , Bower Wendy , Mariman An , Vogelaers Dirk , Depypere Herman , Everaert Karel
Published: March 2021

Objective:

To observe the impact of different hormonal treatment options on nocturia, its causative factors and bother in postmenopausal women.

Methods:

This prospective study recruited 245 postmenopausal women and divided them into four treatment groups based on patient's choice: Estrogen + Progesterone (E+P), Estrogen-only in patients with a prior hysterectomy, tissue-selective estrogen complex (TSEC) and no treatment. Nocturia and its causative factors were observed using two standardized questionnaires before and after treatment: the International Consultation on Incontinence Questionnaire Nocturia Module and the Targeting the individual's Aetiology of Nocturia to Guide Outcomes (TANGO). The results of the Targeting the individual's Aetiology of Nocturia to Guide Outcomes were divided in four influencing topics of which the sum score was calculated.

Results:

A significant reduction in prevalence of nocturia ≥ twice per night was seen after treatment, as the prevalence decreased from 27.7% (59/213) to 16.4% (35/213). Specified per therapy, a significant reduction in nocturnal voiding frequency was observed in patients treated with E+P and TSEC (P = 0.018 and P = 0.018, respectively). This improvement could be explained by a significant reduction in SLEEP sum score in patients treated with E+P and TSEC (P < 0.001, P = 0.013, respectively). Estrogen-only led to a significant change in URINARY TRACT sum score, which is the result of a reduction in urgency prevalence (P = 0.039).

Conclusions:

E+P and TSEC treatment led to a significant reduction in nocturia prevalence and bother in women with ≥ 2 nocturnal voids. This effect is mainly the result of improvement in sleep disorders, however an improvement in bladder disorders can be suggested as well. More research is necessary to confirm these findings.

Video Summary:

http://links.lww.com/MENO/A710.
A prospective controlled study of sexual function and sexually related personal distress up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy
Authors: Islam Rakibul M. , Davis Susan R. , Bell Robin J. , Tejada-Berges Trevor , Wrede Caspar David , Domchek Susan M. , Meiser Bettina , Kirk Judy , Krejany Efrosinia O. , Hickey Martha
Published: March 2021

Objective:

Premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) may impair sexual function, but the nature and degree of impairment and impact of estrogen therapy on sexual function and sexually related personal distress after RRBSO are uncertain.

Methods:

Prospective observational study of 73 premenopausal women at elevated risk of ovarian cancer planning RRBSO and 68 premenopausal controls at population risk of ovarian cancer. Participants completed the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. Change from baseline in sexual function following RRBSO was compared with controls at 12 months according to estrogen therapy use.

Results:

Baseline sexual function domains did not differ between controls and those who underwent RRBSO and subsequently initiated (56.2%) or did not initiate (43.8%) estrogen therapy. At 12 months, sexual desire and satisfaction were unchanged in the RRBSO group compared with controls. After RRBSO, nonestrogen therapy users demonstrated significant impairment in sexual arousal (β-coefficient (95% confidence interval) −2.53 (−4.86 to −0.19), P < 0.03), lubrication (−3.40 (−5.84 to −0.96), P < 0.006), orgasm (−1.64 (−3.23 to −0.06), P < 0.04), and pain (−2.70 (−4.59 to 0.82), P < 0.005) compared with controls. Although sexually related personal distress may have been more likely after RRBSO, irrespective of estrogen therapy use, there was insufficient data to formally test this effect.

Conclusions:

The findings suggest premenopausal RRBSO adversely affects several aspects of sexual function which may be mitigated by the use of estrogen therapy. Further research is needed to understand the effects of RRBSO on sexual function and sexually related personal distress, and the potential for estrogen therapy to mitigate against any adverse effects.
Quantitative study on the efficacy of acupuncture in the treatment of menopausal hot flashes and its comparison with nonhormonal drugs
Authors: Li Ting , Zhang Yi , Cheng Qingqing , Hou Mengyuan , Zheng Xijun , Zheng Qingshan , Li Lujin
Published: March 2021

Objective:

This study aimed to compare the efficacy of acupuncture to that of sham acupuncture, placebo pills, and nonhormonal drugs to provide the necessary quantitative information for establishing medication guidelines for menopausal hot flashes.

Methods:

A comprehensive literature search was performed using public databases. Randomized clinical studies on acupuncture therapy for the treatment of hot flashes in menopausal women were identified. A time-course model was established to describe the efficacy characteristics of acupuncture and sham acupuncture, which were compared with the efficacy of nonhormonal drugs and placebo pills reported in the literature.

Results:

A total of 17 studies involving 1,123 participants were included. The quality of all the studies included in the analysis is medium to high, and there was no obvious risk of bias. It was found that the baseline number of hot flashes was an important factor affecting the efficacy of acupuncture and sham acupuncture. After correcting the baseline to eight hot flashes per day, the frequency of hot flashes decreased from baseline for traditional acupuncture (TA), electro-acupuncture (EA), TA&EA (merger analysis of TA and electro-acupuncture), and sham acupuncture were 3.1 (95% confidence interval [CI]: 2.8-3.4), 3.6 (95% CI: 3.2-4.0), 3.2 (95% CI: 2.9-3.5), and 2.6 (95% CI: 2.2-3.0) times/d at week 8, respectively. Compared with findings reported in the literature, we found the efficacy of electro-acupuncture was comparable to that of selective serotonin reuptake inhibitors/serotonin–norepinephrine reuptake inhibitors and neuroleptic agents such as gabapentin and escitalopram. Furthermore, the efficacy of TA&EA (merged) was significantly higher than that of placebo pills (2.3, 95% CI: 1.8-2.9).

Conclusions:

The efficacy of TA&EA (merged) was higher than that of sham acupuncture and significantly higher than that of placebo pills. The efficacy of electro-acupuncture was higher than that of traditional acupuncture, significantly higher than that of sham acupuncture, and comparable to that of selective serotonin reuptake inhibitors/serotonin–norepinephrine reuptake inhibitors and neuroleptic agents.
A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories
Authors: Fischer Bastian , Lichtenberg Christoph , Müller Lisa , Timm Jörg , Fischer Johannes , Knabbe Cornelius
Published: March 2021

The determination of anti-SARS-CoV-2 neutralizing antibodies (NAbs) is of interest in many respects. High NAb titers, for example, are the most important criterion regarding the effectiveness of convalescent plasma therapy. However, common cell culture-based NAb assays are time-consuming and feasible only in special laboratories. Our data reveal the suitability of a novel ELISA-based surrogate virus neutralization test (sVNT) to easily measure the inhibition-capability of NAbs in the plasma of COVID-19 convalescents. We propose a combined strategy to detect plasma samples with high NAb titers (≥ 1:160) reliably and to, simultaneously, reduce the risk of erroneously identifying low-titer specimens. For this approach, results of the sVNT assay are compared to and combined with those acquired from the Euroimmun anti-SARS-CoV-2 IgG assay. Both assays are appropriate for high-throughput screening in standard BSL-2 laboratories. Our measurements further show a long-lasting humoral immunity of at least 11 months after symptom onset.
Thermal modulation of Zebrafish exploratory statistics reveals constraints on individual behavioral variability
Authors: Goc Guillaume Le , Lafaye Julie , Karpenko Sophia , Bormuth Volker , Candelier Raphaël , Debrégeas Georges
Published: March 2021

Background

Variability is a hallmark of animal behavior. It contributes to survival by endowing individuals and populations with the capacity to adapt to ever-changing environmental conditions. Intra-individual variability is thought to reflect both endogenous and exogenous modulations of the neural dynamics of the central nervous system. However, how variability is internally regulated and modulated by external cues remains elusive. Here we address this question by analyzing the statistics of spontaneous exploration of freely swimming zebrafish larvae, and by probing how these locomotor patterns are impacted when changing the water temperatures within an ethologically relevant range.

Results

We show that, for this simple animal model, five short-term kinematic parameters - interbout interval, turn amplitude, travelled distance, turn probability and orientational flipping rate - together control the long-term exploratory dynamics. We establish that the bath temperature consistently impacts the means of these parameters, but leave their pairwise covariance unchanged. These results indicate that the temperature merely controls the sampling statistics within a well-defined kinematic space delineated by this robust statistical structure. At a given temperature, individual animals explore the behavioral space over a timescale of tens of minutes, suggestive of a slow internal state modulation that could be externally biased through the bath temperature. By combining these various observations into a minimal stochastic model of navigation, we show that this thermal modulation of locomotor kinematics results in a thermophobic behavior, complementing direct gradient-sensing mechanisms.

Conclusions

This study establishes the existence of a well-defined locomotor space accessible to zebrafish larvae during spontaneous exploration, and quantifies self-generated modulation of locomotor patterns. Intra-individual variability reflects a slow diffusive-like probing of this space by the animal. The bath temperature in turn restricts the sampling statistics to sub-regions, endowing the animal with basic thermophobicity. This study suggests that in Zebrafish, as well as in other ectothermic animals, ambient temperature could be used to efficiently manipulate internal states in a simple and ethological way.
The long-time orphan protistMeringosphaera mediterraneaLohmann, 1902 [1903] is a centrohelid heliozoan
Authors: Zlatogursky Vasily V. , Sh□shkin Yegor , Drachko Daria , Burki Fabien
Published: March 2021

Meringosphaerais an enigmatic marine protist without clear phylogenetic affiliation, but it has long been suggested to be a chrysophytes-related autotroph. Microscopy-based reports indicate that it has a worldwide distribution, but no sequence data exists so far. We obtained the first 18S rDNA sequence forM. mediterranea(identified using light and electron microscopy) from the West Coast of Sweden. Observations of living cells revealed granulated axopodia and up to 6 globular photosynthesizing bodies about 2 μm in diameter, the nature of which requires further investigation. The ultrastructure of barbed undulating spine scales and patternless plate scales with a central thickening is in agreement with previous reports. Molecular phylogenetic analysis placedM. mediterraneainside the NC5 environmental clade of Centroplasthelida (Haptista) along with additional environmental sequences, together closely related to Choanocystidae. This placement is supported by similar scales inMeringosphaeraand Choanocystidae. We searched the Tara Oceans 18S-V9 metabarcoding dataset which revealed four OTUs with 95.5-98.5% similarity, with oceanic distribution similar to that based on morphological observations. The current taxonomic position and species composition of the genus are discussed. The planktonic lifestyle ofM. mediterraneacontradicts the view of some authors that centrohelids enter the plankton only temporarily.
Pooled Single-Molecule transcriptomics identifies a giant gene under balancing selection in sunflower
Authors: Badouin Hélène , Boniface Marie-Claude , Pouilly Nicolas , Fuchs Anne-Laure , Vear Felicity , Langlade Nicolas B. , Gouzy Jérôme , Muños Stéphane
Published: March 2021

Genes under balancing selection control phenotypes such as immunity, color or sex, but are difficult to identify. Self-incompatibility genes are under negative frequency-dependent selection, a special case of balancing selection, with up to 30 to 50 alleles segregating per population. We developed a method based on pooled Single-Molecule transcriptomics to identify balanced polymorphisms expressed in tissues of interest. We searched for multi-allelic, non-recombining genes causing self-incompatibility in wild sunflower (Helianthus annuus). A diversity scan in pistil identified a gene,Ha7650b,that displayed balanced polymorphism and colocalized with a quantitative trait locus for self-incompatibility. Unexpectedly,Ha7650bdisplayed gigantism (400 kb), which was caused by increase in intron size as a consequence of suppressed recombination.Ha7650bemerged after a whole-genome duplication (29 millions years ago) followed by tandem duplications and neofunctionalisation.Ha7650bshows expression, genetic location, genomic neighbourhood and predicted function that provide strong evidence that it is involved in self-incompatibility. Pooled Single-Molecule transcriptomics is an affordable and powerful new method that makes it possible to identify diversity and structural outliers simultaneously. It will allow a breakthrough in the discovery of self-incompatibility genes and other expressed genes under balancing selection.
Thermal stress triggers productive viral infection of a key coral reef symbiont
Authors: Grupstra Carsten GB , Howe-Kerr Lauren I , Veglia Alex J , Bryant Reb L , Coy Samantha R , Blackwelder Patricia L , Correa Adrienne MS
Published: March 2021

Climate change-driven ocean warming is increasing the frequency and severity of bleaching events, in which corals appear whitened after losing their dinoflagellate endosymbionts (family Symbiodiniaceae). Viral infections of Symbiodiniaceae may contribute to some bleaching signs, but little empirical evidence exists to support this hypothesis. We present the first temporal analysis of a lineage of Symbiodiniaceae-infecting positive-sense single-stranded RNA viruses (‘dinoRNAVs’) in coral colonies, which were exposed to a 5-day heat treatment (+2.1°C). A total of 124 dinoRNAV major capsid protein gene ‘aminotypes’ (unique amino acid sequences) were detected from five colonies of two closely relatedPocillopora-Cladocopium(coral-symbiont) combinations in the experiment; most dinoRNAV aminotypes were shared between the two coral-symbiont combinations (64%) and among multiple colonies (82%). Throughout the experiment, seventeen dinoRNAV aminotypes were found only in heat-treated fragments, and 22 aminotypes were detected at higher relative abundances in heat-treated fragments. DinoRNAVs in fragments of some colonies exhibited higher alpha diversity and dispersion under heat stress. Together, these findings provide the first empirical evidence that exposure to high temperatures triggers some dinoRNAVs to switch from a persistent to a productive infection mode within heat-stressed corals. Over extended time frames, we hypothesize that cumulative dinoRNAV production in thePocillopora-Cladocopiumsystem could affect colony symbiotic status, for example, by decreasing Symbiodiniaceae densities within corals. This study sets the stage for reef-scale investigations of dinoRNAV dynamics during bleaching events.
Comprehensive patient-level classification and quantification of driver events in TCGA PanCanAtlas cohorts
Authors: Vyatkin Alexey D. , Otnyukov Danila V. , Leonov Sergey V. , Belikov Aleksey V.
Published: March 2021

There is a growing need to develop novel therapeutics for targeted treatment of cancer. The prerequisite to success is the knowledge about which types of molecular alterations are predominantly driving tumorigenesis. To shed light onto this subject, we have utilized the largest database of human cancer mutations – TCGA PanCanAtlas, multiple established algorithms for cancer driver prediction (2020plus, CHASMplus, CompositeDriver, dNdScv, DriverNet, HotMAPS, OncodriveCLUSTL, OncodriveFML) and developed four novel computational pipelines: SNADRIF (Single Nucleotide Alteration DRIver Finder), GECNAV (Gene Expression-based Copy Number Alteration Validator), ANDRIF (ANeuploidy DRIver Finder) and PALDRIC (PAtient-Level DRIver Classifier). A unified workflow integrating all these pipelines, algorithms and datasets at cohort and patient levels was created.

We have found that there are on average 12 driver events per tumour, of which 0.6 are single nucleotide alterations (SNAs) in oncogenes, 1.5 are amplifications of oncogenes, 1.2 are SNAs in tumour suppressors, 2.1 are deletions of tumour suppressors, 1.5 are driver chromosome losses, 1 is a driver chromosome gain, 2 are driver chromosome arm losses, and 1.5 are driver chromosome arm gains. The average number of driver events per tumour increases with age (from 7 to 15) and cancer stage (from 10 to 15) and varies strongly between cancer types (from 1 to 24). Patients with 1 and 7 driver events per tumour are the most frequent, and there are very few patients with more than 40 events. In tumours having only one driver event, this event is most often an SNA in an oncogene. However, with increasing number of driver events per tumour, the contribution of SNAs decreases, whereas the contribution of copy-number alterations and aneuploidy events increases.

Author Summary

By analysing genomic and transcriptomic data from 10000 cancer patients through our custom-built computational pipelines and previously established third-party algorithms, we have found that half of all driver events in a patient’s tumour appear to be gains and losses of chromosomal arms and whole chromosomes. We therefore suggest that future therapeutics development efforts should be focused on targeting aneuploidy. We have also found that approximately a third of driver events in a patient are whole gene amplifications and deletions. Thus, therapies aimed at copy-number alterations also appear very promising. On the other hand, drugs aiming at point mutations are predicted to be less successful, as these alterations are responsible for just a couple of drivers per tumour. One notable exception are patients having only one driver event in their tumours, as this event is almost always a single nucleotide alteration in an oncogene.
Minimizing spectral overlap in multicolor flow cytometry experiments
Authors: Rønn Olsen Lars , Benso Alfredo , Politano Gianfranco , Barnkob Mike Bogetofte
Published: March 2021

Selecting fluorochromes for polychromatic panels for flow cytometry is complex and time-consuming. Poorly designed panels can result in overlap between the emission spectra of the different fluorochromes, making their signals difficult to separate. While assessing all possible panels is simple to do programmatically, the combinatorial complexity of most real world problems renders brute force computation impractical. Here we present a novel complexity optimization algorithm for fast design of minimal spectral overlap fluorochrome combinations. To aid researchers in designing fluorochrome panels we implemented the algorithm in a web server, Spectracular, that also considers instrument laser configuration and allows users to define various constraints related to antibody-fluorochrome availability and marker co-expression.
ENCODING OF LIMB STATE BY SINGLE NEURONS IN THE CUNEATE NUCLEUS OF AWAKE MONKEYS
Authors: Versteeg Christopher , Rosenow Joshua M. , Bensmaia Sliman J. , Miller Lee E.
Published: March 2021

The cuneate nucleus (CN) is among the first sites along the neuraxis where proprioceptive signals can be integrated, transformed, and modulated. The objective of the study was to characterize the proprioceptive representations in CN. To this end, we recorded from single CN neurons in three monkeys during active reaching and passive limb perturbation. We found that many neurons exhibited responses that were tuned approximately sinusoidally to limb movement direction, as has been found for other sensorimotor neurons. The distribution of their preferred directions (PDs) was highly non-uniform and resembled that of muscle spindles within individual muscles, suggesting that CN neurons typically receive inputs from only a single muscle. We also found that the responses of proprioceptive CN neurons tended to be modestly amplified during active reaching movements compared to passive limb perturbations, in contrast to cutaneous CN neurons whose responses were not systematically different in the active and passive conditions. Somatosensory signals thus seem to be subject to a “spotlighting” of relevant sensory information rather than uniform suppression as has been suggested previously.