bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial p53 reactivation is sufficient to induce cancer regression
Authors: Klimovich Boris , Meyer Laura , Merle Nastasja , Neumann Michelle , König Alexander M. , Ananikidis Nikolaos , Keber Corinna U. , Elmshäuser Sabrina , Timofeev Oleg , Stiewe Thorsten
Published: March 2022

Background

Impaired p53 function is one of the central molecular features of a tumor cell and even a partial reduction in p53 activity can increase the cancer risk in mice and men. From a therapeutic perspective it is noteworthy that tumor cells often become addicted to the absence of p53 providing a rationale for developing p53 reactivating compounds to treat cancer patients. Unfortunately, many of the compounds that are currently undergoing preclinical and clinical testing fail to fully reactivate mutant p53 proteins, raising the crucial question: how much p53 activity is needed to elicit a therapeutic effect?

Methods

We have genetically modelled partial p53 reactivation using knock-in mice with inducible expression of the p53 variant E177R. This variant has a reduced ability to bind and transactivate target genes and consequently causes moderate cancer susceptibility. We have generated different syngeneically transplanted and autochthonous mouse models of p53-deficient acute myeloid leukemia and B or T cell lymphoma. After cancer manifestation we have activated E177R expression and analyzed the in vivo therapy response by bioluminescence or magnetic resonance imaging. The molecular response was further characterized in vitro by assays for gene expression, proliferation, senescence, differentiation, apoptosis and clonogenic growth.

Results

We report the conceptually intriguing observation that the p53 variant E177R, which promotes de novo leukemia and lymphoma formation, inhibits proliferation and viability, induces immune cell infiltration and triggers cancer regression in vivo when introduced into p53-deficient leukemia and lymphomas. p53-deficient cancer cells proved to be so addicted to the absence of p53 that even the low-level activity of E177R is detrimental to cancer growth.

Conclusions

The observation that a partial loss-of-function p53 variant promotes tumorigenesis in one setting and induces regression in another, underlines the highly context-specific effects of individual p53 mutants. It further highlights the exquisite sensitivity of cancer cells to even small changes in p53 activity and reveals that changes in activity level are more important than the absolute level. As such, the study encourages ongoing research efforts into mutant p53 reactivating drugs by providing genetic proof-of-principle evidence that incomplete p53 reactivation may suffice to elicit a therapeutic response.
PAciFy Cough—a multicentre, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of pulmonary Fibrosis Cough
Authors: Wu Zhe , Banya Winston , Chaudhuri Nazia , Jakupovic Ira , Maher Toby M. , Patel Brijesh , Spencer Lisa G. , Thillai Muhunthan , West Alex , Westoby John , Wijsenbeek Marlies , Smith Jaclyn , Molyneaux Philip L.
Published: March 2022

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring. Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients’ quality of life. There are no proven effective therapies for IPF-related cough. Whilst morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. PAciFy Cough is a multicenter, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of cough in IPF.

Methods

We will recruit 44 subjects with IPF prospectively from three interstitial lung disease units in the UK, namely the Royal Brompton Hospital, Manchester University NHS Foundation Trust (MFT) and Aintree University Hospital NHS Foundation Trust. Patients will be randomised (1:1) to either placebo twice daily or morphine sulphate 5 mg twice daily for 14 days. They will then crossover after a 7-day washout period. The primary endpoint is the percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective cough monitoring at day 14 of treatment.

Discussion

This multicentre, randomised trial will assess the effect of opioids on cough counts and cough associated quality of life in IPF subjects. If proven to be an effective intervention, it represents a readily available treatment for patients.

Trial registration

The study was approved by the UK Medicines and Healthcare Regulatory Agency (Ref: CTA 21268/0224/001-0001 – EUDRACT 2019-003571-19 – Protocol Number RBH2019/001) on 08 April 2020, in compliance with the European Clinical Trials Directive and the Medicines for Human Use (Clinical Trials) Regulations 2004 and its subsequent amendments. The study was provided with ethical approval by the London Brent Research Ethics Committee (Ref: 20/LO/0368) on 21 May 2020 and is registered with clinicaltrials.gov (NCT04429516) on 12 June 2020, available at https://clinicaltrials.gov/ct2/show/NCT04429516
Study protocol for the Multimodal Approach to Preventing Suicide in Schools (MAPSS) project: a regionally based randomised trial of an integrated response to suicide risk among secondary school students
Authors: Byrne Sadhbh J. , Bailey Eleanor , Lamblin Michelle , McKay Samuel , Pirkis Jane , Mihalopoulos Cathrine , Spittal Matthew J. , Rice Simon , Hetrick Sarah , Hamilton Matthew , Yuen Hok Pan , Lee Yong Yi , Boland Alexandra , Robinson Jo
Published: March 2022

Background

Suicide is the leading cause of death among young Australians, accounting for one-third of all deaths in those under 25. Schools are a logical setting for youth suicide prevention activities, with universal, selective and indicated approaches all demonstrating efficacy. Given that international best practice recommends suicide prevention programmes combine these approaches, and that to date this has not been done in school settings, this study aims to evaluate a suicide prevention programme incorporating universal, selective and indicated components in schools.

Methods

This study is a trial of a multimodal suicide prevention programme for young people. The programme involves delivering universal psychoeducation (safeTALK) to all students, screening them for suicide risk, and delivering internet-based Cognitive Behavioural Therapy (Reframe IT) to those students identified as being at high risk for suicide. The programme will be trialled in secondary schools in Melbourne, Australia, and target year 10 students (15 and 16 year-olds). safeTALK and screening will be evaluated using a single group pre-test/post-test case series, and Reframe IT will be evaluated in a Randomised Controlled Trial. The primary outcome is change in suicidal ideation; other outcomes include help-seeking behaviour and intentions, and suicide knowledge and stigma. The programme’s cost-effectiveness will also be evaluated.

Discussion

This study is the first to evaluate a suicide prevention programme comprising universal, selective and indicated components in Australian schools. If the programme is found to be efficacious and cost-effective, it could be more widely disseminated in schools and may ultimately lead to reduced rates of suicide and suicidal behaviour in school students across the region.
Establishment of bovine 3D enteroid-derived 2D monolayers
Authors: Sutton Kate M. , Orr Brigid , Hope Jayne , Jensen Stina R. , Vervelde Lonneke
Published: March 2022

Three-dimensional (3D) intestinal enteroids are powerful in vitro models for studying intestinal biology. However, due to their closed structure direct access to the apical surface is impeded, limiting high-throughput applications of exogenous compounds and pathogens. In this study, we describe a method for generating confluent 2D enteroids from single-cell suspensions of enzymatically-dissociated ileum-derived bovine 3D enteroids. Confluent monolayers were first achieved using IntestiCult media but to establish a defined, cost-effective culture media, we also developed a bovine enteroid monolayer (BEM) medium. The monolayers cultured in BEM media proliferated extensively and formed confluent cell layers on both Matrigel-coated plastic plates and transwell inserts by day 3 of culture. The 2D enteroids maintained the epithelial cell lineages found in 3D enteroids and ileum tissue. In addition, the monolayers formed a functional epithelial barrier based on the presence of the adherens and tight junction proteins, E-cadherin and ZO-1, and electrical resistance across the monolayer was measured from day 3 and maintained for up to 7 days in culture. The method described here will provide a useful model to study bovine epithelial cell biology with ease of access to the apical surface of epithelial cells and has potential to investigate host–pathogen interactions and screen bioactive compounds.
Microwave wireless power transmission technology index system and test evaluation methods
Authors: Wang Changfu , Xu Wanli , Zhang Chunlin , Wang Mengyi , Wang Xudong
Published: March 2022

Microwave wireless power transmission technology has broad application prospects in improving the endurance and range of unmanned equipment. It is also of great significance in the field of the Internet of things, which can effectively solve the problem of energy supply for devices in the Internet of things. In addition, using vehicle-mounted microwave wireless power transmission to power multi-objective unmanned aerial vehicle swarms and to build an air-ground integrated power transmission network. In this study, the corresponding technical index system and test evaluation methods, which are conducive to promoting the development and progress of this technology, were established. The topology of a microwave wireless power transmission system was analyzed, and technical evaluation indices were developed for microwave wireless power transmission systems, signal generators, power amplifiers, transceiver antennas, and rectifier circuits. Test evaluation methods were established consisting of test equipment, methods, and processes to provide powerful technical means for the development of microwave wireless power transmission systems.
A new method of identifying key industries: a principal component analysis
Authors: Tsoulfidis Lefteris , Athanasiadis Ioannis
Published: March 2022

This article using the principal components analysis identifies key industries and groups them into particular clusters. The data come from the US benchmark input–output tables of the years 2002, 2007, 2012 and the most recently published input–output table of the year 2019. We observe some intertemporal switches of industries both between and within the top clusters. The findings further suggest that structural change is a slow-moving process and it takes time for some industries to move from one cluster to the other. This information may be proved important in the designation of effective economic policies by targeting key industries and also for the stability properties of the economic system.
The leading role of perception: the FACOPA model to comprehend innovation adoption
Authors: Vecchio Yari , De Rosa Marcello , Pauselli Gregorio , Masi Margherita , Adinolfi Felice
Published: March 2022

In this work, we explore the link between the perception of complexity and the possibility of adopting precision agricultural tools (PATs). Many studies have analysed the role of perception, mostly considering it a determinant of adoption on the same level as other contextual factors. In contrast, this study contributes by assuming that farmers' perceived complexity is the main factor influencing their propensity to innovate and should be analysed on a different level. Starting from this assumption, a new theoretical model is proposed with the aim of studying the “factors–perception of complexity–adoption” (FACOPA) process. To test the validity of our hypothesis, a survey is conducted based on a purposive sample of 285 farmers. First, a linear regression model permits us to identify determinants of the perception of complexity. Then, a multinomial logistic model is used to determine which aspects of perceived complexity may affect the choice to adopt precision farming tools made by three different types of agricultural entrepreneurs: adopters, non-adopters, and planners. First, the linear regression results show that socio-structural variables have a logical relationship with perceived complexity, with age, farm size, the intensity of information and the intensity of work being significant. Then, the multinomial logistic model highlights that non-adopters perceive almost all aspects of complexity as barriers to adoption. Planners show a lower perception of complexity than non-adopters, with complexity being determined by financial and network aspects. The results provide interesting suggestions for policy-makers. Indeed, the FACOPA model offers insights into an intervention framework in which policy measures can be diversified to disseminate PATs based on farmer categories. Non-adopters require a broader set of policy instruments, while planners should be encouraged to become adopters through financial support and the activation of innovation networks.
Longitudinal measurement of growth in vocabulary size using Rasch-based test equating
Authors: Akase Masaki
Published: March 2022

The purpose of this study is to equate and further validate three forms of the vocabulary size test (VST) created by Aizawa and Mochizuki (2010). These three forms, VST 1, 2, and 3, were administered to a cohort of 189 high school students ranging in age from 16 to 18 in April of their 1st, 2nd, and 3rd year of high school. Although these alternate forms were designed to be of equal difficulty, formal equating of the three forms was never carried out. In order to verify whether gains in test scores were due to growth in vocabulary size or differences in difficulty among the three forms, a fourth form comprised of items selected from VST 1–3 was created and administered in December of year 3. The four test forms were then equated using Rasch analysis, placing persons and items on a single, uniform logit scale. The results indicated that (1) the three original forms of the VST all showed good fit to the Rasch model, (2) differences in test difficulty among the original three forms were minor, and (3) the four VST forms, linked via a single Rasch analysis, can be appropriately used for estimating gains in students’ VS across their high school career. In addition, follow-up analyses indicated considerable overlap in item difficulty among word frequency bands, suggesting that word frequency was not the sole indicator of difficulty of vocabulary items, and that learner progress in vocabulary learning tended to be uniform and parallel across all frequency bands. Overall, the study illustrates a method for creating a valid and reliable measure of growth in VS over an extended period of time and provides insight into the relationships among word frequency, word difficulty, and progress in vocabulary learning.
Laser ablation inductively coupled plasma mass spectrometry analysis of potash and m-Na-Al glasses in China- using Kernel methods for trace element analysis
Authors: Ma Qian , Pollard A. Mark , Yu Yifan , Li Zhuanjie , Liao Linling , Wang Long , Li Man , Cai Luwu , Ping Li , Wen Rui
Published: March 2022

Monochrome drawn beads were widely circulated in South and Southeast Asia as early as the second century BC. This article aims to identify the glass beads unearthed from different sites in China and discuss their possible sources. Twenty-seven mineral soda alumina (m-Na-Al) glass and eighty-seven potash glass beads unearthed in different provinces in China were analysed by Laser Ablation Inductively Coupled Plasma Mass Spectrometry. The trace element analysis through Multivariate Kernel Density Estimation and Maximum Mean Discrepancy indicates the silica sources of m-Na-Al glass and most of the potash glass unearthed from Guangxi are identical. They were presumably produced somewhere in northeastern India or Southeast Asia and exported through the Maritime Silk Road. The silica sources of m-Na-Al glass in Henan and the rest of the potash glasses are geologically close. They were likely produced in southern India or Sri Lanka and exported through the North and Southwest Silk Roads. Future research on isotopic analysis will reveal more information about primary/secondary glass production in China, South and Southeast Asia.
Severe weather disasters in China linked to solar activity during 1-1825 Common Era
Authors: Liu Jann-Yenq , Chen Yuh-Ing , Lee Po-Han , Huang Chi-Shen , Fang Tzu-Wei
Published: March 2022

Historical records truthfully document human life and environment associated with climate changes. We quantify official historical records of China dating back last 2000 years to examine the disasters due to anomalous temperatures of cold or hot, irregular precipitations of wet or dry, and floods in inland/coastal or Northern/Southern areas in four seasons that possibly linked to solar activities during 1-1825 CE (Common Era). It is found that the proportion of disaster years is positively associated with the time periods, and therefore, both the cases with high and low solar activity (HSA and LSA) leading are under study. Statistical results show that extreme cold weather occurs particularly in the Winter and Spring during LSA periods. Irregularities precipitations, including heavy rain/hail/snow and severe drought are significantly frequent during LSA periods, while floods on inland and coastal river basins tend to occur more frequently in LSA and HSA periods, respectively. The disasters owing to irregularities precipitations and floods frequently happen in Summer and Autumn, which suggests that the irregular precipitations could cause the floods. All the disasters occur significantly in the Northern China, which suggests the climate boundary of the Qinling–Huaihe Line along at about 33°N being essential. In total, all the disasters due to the anomalously cold temperatures, irregular precipitations, and floods tend to occur during the LSA periods.
Getting old beats the alternative
Authors: Kessler Allison
Published: March 2022

Getting old is hard, but it beats the alternative. This commentary explores some of the challenges of aging with a physical disability and the considerations taken to prevent further functional decline or injury during the aging process.
Development and feasibility testing of a physical activity intervention for youth with anxiety and depression: a study protocol
Authors: Kodal Arne , Muirhead Fiona , Reilly John J. , Wergeland Gro Janne H. , Thorsen Paul Joachim Bloch , Bovim Lars Peder , Elgen Irene Bircow
Published: March 2022

Background

Anxiety and depressive disorders in children and adolescents are highly prevalent and account for more than half of all youth psychiatric disorders. Left untreated, anxiety, and depression lead to numerous detrimental outcomes, including reduced quality of life, psychiatric, and somatic comorbidity and even reduced lifespan. This puts a large strain on child and adolescent mental healthcare services (CAMHS) to provide effective treatments. However, even when provided the best evidence-based treatment, between 40–50% of patients continue to report significant symptom burdens. Thus, there is an immediate need for supplemental and/or new treatment approaches. Physical activity as a supplementary treatment may be such an approach. However, research investigating this approach within this population is scant. This protocol paper describes the development and feasibility trial of a physical activity-based intervention targeting anxiety and depressive symptoms in youth treated in CAMHS.

Methods/design

The study is based on the UK Medical Council Research Framework (MRC) for developing and evaluating complex interventions. Feasibility and acceptability of the physical activity intervention (confident, active, and happy youth) will be evaluated in an uncontrolled open-label trial using qualitative and quantitative data. Twenty youths with anxiety and/or depressive symptoms will be recruited. Acceptability of assessment procedures, the intervention, and perceived benefits and barriers to participation will be assessed, and qualitative interviews with participants, caregivers, and referring specialists will explore contextual and practical factors associated with intervention delivery. Physical activity will be measured using the Actigraph GT3X+ monitor at baseline, and post-intervention and change in anxiety and depression will be assessed.

Discussion

This study will contribute to the development of supplementary physical treatment interventions for youth with anxiety and depression in contact with CAMHS. The goal is to examine new avenues of treatment that ultimately may improve upon current treatment outcomes of anxiety and depression. This work will be in preparation for a future definitive randomized controlled trial (RCT) of this approach, in line with the MRC Framework.

Trial registration

ClnicalTrials.gov, NCT05049759. Registered on August 19, 2021. Retrospectively registered.
Multiple ways for the same destination: bone regeneration
Authors: Kim Seong-Gon
Published: March 2022

The regeneration of the bone is a challenging topic for maxillofacial plastic and reconstructive surgeons. For successful bone regeneration, timely providing of essential components is prerequisite. They are cellular components (osteoblasts, osteoclasts, and immune cells), extracellular matrix, and inorganic components (calcium and phosphate). Any deficient component can be provided from outside as a graft. Accordingly, there are many ways for successful bone regeneration. Selection of appropriate methods in an individualized situation is important.
Efficacy of low-fat milk and yogurt fortified with vitamin D3 on systemic inflammation in adults with abdominal obesity
Authors: Sharifan Payam , Rashidmayvan Mohammad , Khorasanchi Zahra , Darroudi Susan , Heidari Azam , Hoseinpoor Fatemeh , Vatanparast Hassan , Safarian Mohamad , Eslami Saeid , Afshari Asma , Asadi Zahra , Ghazizadeh Hamideh , Bagherniya Mohammad , Khedmatgozar Hamed , Ferns Gordon , Rezaie Mitra , Mobarhan Majid Ghayour
Published: March 2022

Background

The prevalence of vitamin D deficiency is increasing globally and is associated with an increased risk of metabolic syndrome, autoimmune disease, and cardiovascular disease. Vit D deficiency is also associated with increased systemic inflammation. The current study aimed to determine the efficacy of low-fat milk and yogurt fortified with 1500 IU nano-encapsulated vitamin D, on systemic inflammation in abdominal obese participants.

Method

This multi-center study was conducted using a 2.5-month parallel total-blind randomized clinical trial design. Two hundred and eighty nine subjects were allocated to four groups: low-fat milk fortified by 1500 IU nano-encapsulated vitamin D3 (200 mL/day). Simple milk (200 mL/day), low-fat yogurt fortified by 1500 IU nano-encapsulated vitamin D3 (150 g/day), and simple yogurt (150 g/day).

Results

The results showed that serum levels of neutrophils, lymphocytes, platelets and red blood cell distribution width (RDW) were significantly lower before and after the intervention in fortified dairy groups. The results showed that serum levels of neutrophils, lymphocytes, platelets, and RDW before and after intervention in the fortified dairy groups were significantly lower (p < 0.05). The values of = neutrophil to lymphocyte ratio (NLR), platelets to lymphocyte ratio, and RDW to platelets ratio (RPR) reduced significantly in the fortification group (p < 0.05).

Conclusion

Fortification with nano-encapsulated vitamin D3 of dairy products may decrease inflammation in individuals with abdominal obesity.
Electrical power behavioral usage in public institutions and its intervention: a case of tanzania higher learning institutions
Authors: Bazila Simon , Kalinga Ellen , Ibwe Kwame , Abdalla Abdi T.
Published: March 2022

Public institutions in developing countries, taking Tanzania as an example, are facing huge electricity consumption bills caused by inefficient utilization of electrical power. The causes of inefficient power usage can be due to the users’ behavioral and inadequacy of technology deployment in electric controlling infrastructure. This study explores the users’ behavior and the consequences of inefficient power utilization in Tanzania Higher Learning Institutions (HLIs). Around 85% of the sampled participants in the selected HLIs were least concerned with power saving strategies while using office facilities. The study reveals that inefficient energy consumption may result in high electrical power bills, unnecessary energy waste, psychological effects caused by inability to pay electrical bills and distress resulting from frequent power outages. Besides, the study proposes both behavioral- and technological-based interventions for electrical power saving in HLIs.
Gene polymorphisms of Interleukin 6 (−174 G/C) and transforming growth factor β-1(+915 G/C) in ovarian cancer patients
Authors: Almolakab Zainab M. , El-Nesr Khalid A. , Mohamad Hassanin Ehab Hassanin , Elkaffas Rasha , Nabil Ahmed
Published: March 2022

Background

In the study on hand, we investigated the effect of IL-6 (−174 G/C; rs 1800795) and TGF-β1 (+915G/C; rs 1800471) gene polymorphisms on the susceptibility to Ovarian Cancer and their effect on plasma levels. IL-6 (−174 G/C) SNP was analyzed using mutagenically separated polymerase chain reaction (MS-PCR) while TGF-β1 +915G/C (codon 25) SNP was investigated by the sequence-specific primer polymerase chain reaction (SSP-PCR). An enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-6 and TGF-β1 plasma levels in 48 ovarian cancer patients and 48 normal controls.

Results

Regarding IL 6 (−174 G/C), a significant increase in CC and GC+CC genotypes parallel with the C allele was considered as risk factors for ovarian cancer; on the other hand, the G allele was considered as a protective factor for ovarian cancer. TGF-β1 (+915G/C) investigations showed a significant elevation in GC and GC+CC genotypes which can be considered as a risk factor for ovarian cancer. Plasma IL-6 and TGF-β1 were higher in ovarian cancer patients compared with controls. No specific genotype or allele could be responsible for the elevation of TGF-β1 in ovarian cancer patients’ plasma, while the highest significant value for IL6 in subjects carrying GG and CC genotypes in comparison with GC genotype.

Conclusions

This study supports an association of IL6 (−174G/C) and TGF-β1 (+915G/C) gene polymorphisms with the susceptibility to ovarian cancer.
Evaluation of periostin, fibronectin and tenascin-C in patients chronic otitis media with cholesteatoma
Authors: Birinci Mehmet , Terzi Suat , Demir Emine , Çeliker Metin , Okçu Oğuzhan , Arpa Medeni , Çelebi Özlem , Özergin Zerrin , Dursun Engin
Published: March 2022

Background

Although many studies have investigated the mechanisms of cholesteatoma formation, its pathogenesis remains unclear. The aim of this study was to evaluate the levels of periostin, fibronectin and tenascin-C, which are involved in many mechanisms, such as cell adhesion, cell differentiation, inflammation, fibrosis, angiogenesis and cell proliferation, in patients with chronic otitis media (COM). A total of 80 participants, 65 COM patients undergoing surgery and 15 healthcare personnel volunteers serving as controls, were included in this study. The participants were divided into four groups: cholesteatoma, granulation, avivation and control group. The serum periostin, fibronectin and tenascin-C levels of all participants were determined biochemically. Histopathological evaluation of tissue samples and 20 skin samples used as controls was performed by immunohistochemistry.

Results

Of the 65 patients, 22 presented with cholesteatoma, 15 with granulation tissue and 28 with the edge of the tympanic membrane perforation freshening tissue. There were no significant differences in serum periostin, fibronectin and tenascin-C levels between the groups. In the immunohistochemical evaluation, fibronectin and periostin staining was significantly more intense in the cholesteatoma group than in the other groups (p = 0.001). Epithelial tenascin-C staining was significantly more intense in the avivation group than in the other groups (p = 0.041).

Conclusion

The levels of periostin and fibronectin were higher in cholesteatoma tissue than in other forms of chronic otitis and skin tissue. This suggests that they may be involved in the mechanism of cholesteatoma formation. These proteins could be used as biomarkers in the diagnosis and treatment of cholesteatoma.
Is it really about freedom of thought?
Authors: Drescher Jack
Published: March 2022

This opinion piece responds to Marcus Evans's ‘Freedom to Think’ regarding treating adolescents diagnosed with gender dysphoria (DSM)/gender incongruence (ICD). Evans notes not everything is known about GD/GI, particularly its ‘causes’. Although correct, he presents this fact as a rationale for delaying treatment for all children presenting with GD/GI symptoms. However, Marcus does not specify how long such prolonged evaluations should last nor does he have much of an evidence base to support his recommendation. This author believes delaying treatment for GD/GI adolescents who need it for the benefit of children who ‘aren’t really’ transgender is an ethically troubling issue.
Same-Cell Co-Occurrence of RAS Hotspot and BRAF V600E Mutations in Treatment-Naive Colorectal Cancer
Authors: Gularte-Mérida Rodrigo , Smith Shaleigh , Bowman Anita S. , da Cruz Paula Arnaud , Chatila Walid , Bielski Craig M. , Vyas Monika , Borsu Laetitia , Zehir Ahmet , Martelotto Luciano G. , Shia Jinru , Yaeger Rona , Fang Fang , Gardner Rui , Luo Ruibang , Schatz Michael C. , Shen Ronglai , Weigelt Britta , Sánchez-Vega Francisco , Reis-Filho Jorge S. , Hechtman Jaclyn F.
Published: March 2022

PURPOSE

Mitogen-activated protein kinase pathway–activating mutations occur in the majority of colorectal cancer (CRC) cases and show mutual exclusivity. We identified 47 epidermal growth factor receptor/BRAF inhibitor-naive CRC patients with dual RAS hotspot/ BRAF V600E mutations (CRC-DD) from a cohort of 4,561 CRC patients with clinical next-generation sequencing results. We aimed to define the molecular phenotypes of the CRC-DD and to test if the dual RAS hotspot/BRAF V600E mutations coexist within the same cell.

MATERIALS AND METHODS

We developed a single-cell genotyping method with a mutation detection rate of 96.3% and a genotype prediction accuracy of 92.1%. Mutations in the CRC-DD cohort were analyzed for clonality, allelic imbalance, copy number, and overall survival.

RESULTS

Application of single-cell genotyping to four CRC-DD revealed the co-occurrence of both mutations in the following percentages of cells per case: NRAS G13D/ KRAS G12C, 95%; KRAS G12D/ NRAS G12V, 48%; BRAF V600E/ KRAS G12D, 44%; and KRAS G12D/ NRAS G13V, 14%, respectively. Allelic imbalance favoring the oncogenic allele was less frequent in CRC-DD (24 of 76, 31.5%, somatic mutations) compared with a curated cohort of CRC with a single-driver mutation (CRC-SD; 119 of 232 mutations, 51.3%; P = .013). Microsatellite instability–high status was enriched in CRC-DD compared with CRC-SD (23% v 11.4%, P = .028). Of the seven CRC-DD cases with multiregional sequencing, five retained both driver mutations throughout all sequenced tumor sites. Both CRC-DD cases with discordant multiregional sequencing were microsatellite instability–high.

CONCLUSION

Our findings indicate that dual-driver mutations occur in a rare subset of CRC, often within the same tumor cells and across multiple tumor sites. Their presence and a lower rate of allelic imbalance may be related to dose-dependent signaling within the mitogen-activated protein kinase pathway.
The analysis of efficiency for high-dimensional quantum secure direct communications under atmospheric turbulence
Authors: Niu Jialei , Liu Xin-Chang
Published: March 2022

Recently, there is a tremendous attention on the high-dimensional quantum information processing using the orbital angular momentum (OAM) of photons. It provides an efficient method to increase the capacity of quantum channel. However, OAM is very vulnerable to atmospheric turbulence, resulting in phase distortion and, therefore, leading to information leakage during quantum communications. On the other hand, quantum secure direct communications (QSDC) define an efficient way of information exchange through quantum channels directly. Here in this work, by combining the applications of OAM states of photons as the information carrier with the QSDC, we analyze the performance of the high-dimensional quantum secure direct communication protocol based on encoding the information on the single photon OAM state under the condition of free space channel. Numerically, we discussed the performance of OAM states QSDC under atmospheric turbulence, and mainly calculated the influence of cross-talk caused by phase fluctuation on the system. We draw the conclusion that under the weak turbulence, when the beam waist

and the Fried parameter r become comparable, the information capacity will decrease sharply.
Prefixed-threshold real-time selection for free-space phase-matching quantum key distribution
Authors: Yu Yang , Wang Le , Zhao Shengmei , Mao Qianping
Published: March 2022

Phase-matching quantum key distribution (PM-QKD), a practical version of twin-field quantum key distribution (TF-QKD), is able to surpass the linear bound without quantum repeaters. Implementing PM-QKD through free space can guarantee two parties to share unconditionally secure keys between ground stations and mobile platforms. However, atmospheric turbulence (AT) in the free-space channel would decrease the secure key rate (SKR) since it would cause fluctuations of transmittances. Two works we do are presented in this paper. First, for simplicity and generality, we derive the SKR for 4-intensity PM-QKD with asymmetric channel transmittances. Secondly, we apply the observable model of the prefixed-threshold real-time selection (P-RTS) method to mitigate the effect of AT in PM-QKD. Here, the authorized parties predetermine the threshold of transmittances and use it to select the signals while monitoring the real-time transmittances. The results show that the performance of PM-QKD in free space is severely degraded by AT, while P-RTS can reduce the impact of AT, making it transmit more than 3 times as long the distance and have a 3.37 times as large SKR at a distance of 50 km.
Metastatic Differentiated Thyroid Cancer Survival Is Unaffected by Mode of Preparation for 131I Administration
Authors: Gomes-Lima Cristiane J , Chittimoju Sanjita , Wehbeh Leen , Dia Sunita , Pagadala Prathyusha , Al-Jundi Mohammad , Jhawar Sakshi , Tefera Eshetu , Mete Mihriye , Klubo-Gwiezdzinska Joanna , Van Nostrand Douglas , Jonklaas Jacqueline , Wartofsky Leonard , Burman Kenneth D
Published: March 2022

Context

Recombinant human thyrotropin (rhTSH) is currently not Food and Drug Administration approved for the treatment of high-risk patients with differentiated thyroid cancer (DTC).

Objective

The goal of our study was to compare the outcomes in higher-risk patients with metastatic DTC prepared for radioiodine (RAI) therapy with rhTSH vs thyroid hormone withdrawal (THW).

Methods

A retrospective chart review was performed of patients with metastatic DTC in follow-up at MedStar Washington Hospital Center and MedStar Georgetown University Hospital from 2009 to 2017. Patients were divided according to their preparation for RAI therapy, with assessment of progression-free survival (PFS) and overall survival (OS).

Results

Fifty-five patients with distant metastases (16 men, 39 women) were prepared for RAI therapy exclusively either with rhTSH (n = 27) or with THW (n = 28). There were no statistically significant differences between the groups regarding clinicopathological features and history of RAI therapies. The median follow-up time for patients with rhTSH-aided therapies was 4.2 years (range, 3.3-5.5 years) and for patients with THW-aided therapies was 6.8 years (range, 4.2-11.6 years) (P = .002). Multivariate analysis showed that the method of thyrotropin stimulation was not associated with a difference in PFS or OS.

Conclusion

As has been shown previously for low-risk DTC, this study indicates that the mode of preparation for RAI therapy does not appear to influence the outcomes of patients with metastatic DTC. PFS and OS were similar for patients with THW-aided or rhTSH-aided RAI therapies.
Attenuated Metabolic and Cardiorespiratory Responses to Isoenergetic High-Intensity Interval Exercise of Short Versus Long Bouts
Authors: BOGDANIS GREGORY C. , STAVRINOU PINELOPI S. , TSIRIGKAKIS SPYRIDON , MOUGIOS VASSILIS , ASTORINO TODD A. , MASTORAKOS GEORGE
Published: March 2022

Purpose

To compare the metabolic, cardiorespiratory and perceptual responses to three isoenergetic high-intensity interval exercise (HIIE) protocols of different bout duration and an isoenergetic continuous exercise protocol.

Methods

Eleven healthy males (age, 28 ± 6 yr) performed four 20-min cycling trials of equal mean power output 1 wk apart. Participants cycled either continuously (CON) or intermittently with 10 s (HIIE10), 30 s (HIIE30), or 60 s (HIIE60) bouts at intensities corresponding to 49% (CON) or 100% of power at peak oxygen uptake (V̇O2peak). Recovery intervals during the HIIE trials were 15, 45, and 90 s, respectively.

Results

Average V̇O2 was similar in the HIIE trials (2.29 ± 0.42, 2.20 ± 0.43, and 2.12 ± 0.45 L·min−1, for HIIE10, HIIE30, and HIIE60, respectively), whereas in CON (2.02 ± 0.38 L·min−1), it was lower than HIIE10 (P = 0.002) and HIIE30 (P = 0.043). Average pulmonary ventilation (VE) was higher in HIIE60 compared with HIIE10, HIIE30, and CON (75.8 ± 21.8 L·min−1 vs 64.1 ± 14.5 L·min−1, 64.1 ± 16.2 L·min−1, and 54.0 ± 12.5 L·min−1, respectively, P < 0.001). The peak values and oscillations of V̇O2 and VE in HIIE60 were higher compared with all other trials (P < 0.001). Blood lactate concentration was higher in HIIE60 compared with HIIE10, HIIE30, and CON from the fifth minute onward, reaching 12.5 ± 3.5, 7.2 ± 2.1, 7.9 ± 2.9, and 4.9 ± 1.6 mmol·L−1, respectively, at the end of exercise (P < 0.001). RPE was higher and affective responses were lower in HIIE60 compared with all other trials toward the end of exercise (P < 0.001).

Conclusions

These findings highlight the importance of bout duration in HIIE, since shorter bouts resulted in attenuated metabolic and cardiorespiratory responses, lower RPE and feelings of displeasure compared with a longer bout, despite equal total work, duration, and work-to-recovery ratio. These results may have implications for the prescription of HIIE in various populations.
The limits of human microRNA annotation have been met
Authors: Fromm Bastian , Zhong Xiangfu , Tarbier Marcel , Friedländer Marc R. , Hackenberg Michael
Published: March 2022

Over the last few years, the number of microRNAs in the human genome has become a controversially debated issue. Several publications reported thousands of putative novel microRNAs not included in the curated microRNA gene database MirGeneDB and the repository miRBase. Recently, by using sequencing of ∼300 human tissues and cell lines, the human RNA atlas, an expanded inventory of human RNA annotations, was published, reporting thousands of putative microRNAs. We, the developers of established microRNA prediction tools and hosts of MirGeneDB, raise concerns about the frequently applied prediction and functional validation strategies, briefly discussing the drawbacks of false positive detections. By means of quantifying well-established biogenesis-derived features, we show that the reported novel microRNAs essentially represent false-positives and argue that the human microRNA complement, at about 550 microRNA genes, is already near complete. Output of available tools must be curated as false predictions will misguide scientists looking for biomarkers or therapeutic targets.
Is orgasmic meditation a form of sex?: practitioners of orgasmic meditation view the practice as significantly more similar to meditation than to sex or fondling
Authors: Siegel Vivian , Roth Caryn , Bolaza Elisabeth , Emmert-Aronson Benjamin , Griggs Caroline
Published: March 2022

Background: Orgasmic Meditation (OM) is a structured, partnered meditative practice in which one person, who can be any gender, strokes the clitoris of their partner for 15 minutes. As such, it resembles a sexual activity. OM is taught as a practice that is distinct from sex, and we wondered whether people who engage in OM actually maintain that distinction themselves.

Methods: We conducted an online convenience sample survey including qualitative open-ended text questions and quantitative Likert-style questions that was distributed to email listservs for practitioners of OM. In the study, 414 participants completed the 30-item questionnaire including questions designed to differentiate the potentially related concepts of OM, seated meditation, fondling, and sex, as bases for comparison.

Results: Participants reported that they strongly agreed that OM is not fondling or sex, giving an average Likert-type rating of 4.55 and 4.65, respectively. Participants disagreed most strongly with the statements “OM is Sex,” and “OM is Fondling,” with average ratings of 1.42 and 1.48, respectively (strongly disagree). There was also high disagreement with the statement “OM is not mediation,” with a rating of 1.53.

Conclusion: The quantitative results of this mixed methods study show that OM practitioners view the practice as significantly more similar to meditation than to sex or fondling. These results were consistent, regardless of whether the question was asked in the positive or negative or whether OM was being compared to one behavior individually or to multiple behaviors at the same time. The distinction between OM and sex/fondling rapidly becomes more pronounced as practitioners complete more OMs. This suggests that the novelty of genital touching in meditation may diminish over time, as practitioners get used to the more alternative point of focus. The results of this study have implications for the practice and how it is approached and regulated.
Dataset of the adoption of digital tools for research sharing among academics in African Varsities during the COVID-19 pandemic in 2020
Authors: Owan Valentine Joseph , Uzoamaka Duruamaku-Dim Jennifer , Nonyelum Odigwe Francisca , Owan Mercy Valentine
Published: March 2022

This dataset was collected from a total of 1,977 university lecturers across 24 African countries, that were purposively targeted due to their level of exposure to scholarly publications. The dataset was collected through an online survey that was sent to respondents through email, WhatsApp, and the Association of African Universities Telegram group. The questionnaire was designed by the researchers and validated by five experts for face and content validity. The demographic information of the data was analysed and the softcopy of the data uploaded to the Mendeley database for easy retrieval after deidentification (see Data Availability statement). The associated questionnaire can be found in the extended data. In Africa, this appears to be the broadest dataset associated with academics’ perception of utilizing digital platforms for research sharing. This implies that scholars can use this dataset to quantitatively analyse the extent to which different digital tools are being utilized for research communication. Considering the current restrictions on in-person social gatherings due to COVID-19, researchers working on related studies may readily utilize this set of data, saving time and cost. A comprehensive but non-exhaustive number of 20 digital tools were assessed based on academics' awareness and current engagement with them, and the challenges they have faced using them. This offers a wide range of areas for studies to be anchored. Furthermore, researchers interested in specific digital tools can also evaluate the extent to which academic staff in African universities are aware of and willing to utilize them for research dissemination. This data will enable scholars and researchers in Africa and beyond to understand the extent to which academics in varsities are willing to adopt digital repositories for research sharing in the context of Africa.
Non-invasive health prediction from visually observable features
Authors: Khong Fan Yi , Connie Tee , Goh Michael Kah Ong , Wong Li Pei , Teh Pin Shen , Choo Ai Ling
Published: March 2022

Background: The unprecedented development of Artificial Intelligence has revolutionised the healthcare industry. In the next generation of healthcare systems, self-diagnosis will be pivotal to personalised healthcare services. During the COVID-19 pandemic, new screening and diagnostic approaches like mobile health are well-positioned to reduce disease spread and overcome geographical barriers. This paper presents a non-invasive screening approach to predict the health of a person from visually observable features using machine learning techniques. Images like face and skin surface of the patients are acquired using camera or mobile devices and analysed to derive clinical reasoning and prediction of the person’s health.

Methods: In specific, a two-level classification approach is presented. The proposed hierarchical model chooses a class by training a binary classifier at the node of the hierarchy. Prediction is then made using a set of class-specific reduced feature set.

Results: Testing accuracies of 86.87% and 76.84% are reported for the first and second-level classification. Empirical results demonstrate that the proposed approach yields favourable prediction results while greatly reduces the computational time.

Conclusions: The study suggests that it is possible to predict the health condition of a person based on his/her face appearance using cost-effective machine learning approaches.
The pathogenicity of blood stream and central nervous system forms of Trypanosoma brucei rhodesiense trypanosomes in laboratory mice: a comparative study
Authors: Ndungu Kariuki , Thuita John , Murilla Grace , Kagira John , Auma Joanna , Mireji Paul , Ngae Geoffrey , Okumu Paul , Gitonga Purity , Guya Samuel , Mdachi Raymond
Published: March 2022

Background: Human African trypanosomiasis (HAT) develops in two stages namely early stage when trypanosomes are found in the blood and late stage when trypanosomes are found in the central nervous system (CNS). The two environments are different with CNS environment reported as being hostile to the trypanosomes than the blood environment. The clinical symptoms manifested by the disease in the two environments are different. Information on whether blood stream are pathologically different from CNS trypanosomes is lacking. This study undertook to compare the inter-isolate pathological differences caused by bloodstream forms (BSF) and central nervous system (CNS) of five Trypanosoma brucei rhodesiense (Tbr) isolates in Swiss white mice.

Methods: Donor mice infected with each of the five isolates were euthanized at 21 days post infection (DPI) for recovery of BSF trypanosomes in heart blood and CNS trypanosomes in brain supernatants. Groups of Swiss white mice (n = 10) were then infected with BSF or CNS forms of each isolate and monitored for parasitaemia, packed cell volume (PCV), body weight, survivorship, trypanosome length, gross and histopathology characteristics.

Results: Amplification of SRA gene prior to trypanosome morphology and pathogenicity studies confirmed all isolates as T. b. rhodesiense.  At 21 DPI, CNS trypanosomes were predominantly long slender (LS) while BSF were a mixture of short stumpy and intermediate forms. The density of BSF trypanosomes was on average 2-3 log-scales greater than that of CNS trypanosomes with isolate KETRI 2656 having the highest CNS trypanosome density.

Conclusions: The pathogenicity study revealed clear differences in the virulence/pathogenicity of the five (5) isolates but no distinct and consistent differences between CNS and BSF forms of the same isolate. We also identified KETRI 2656 as a suitable isolate for acute menigo- encephalitic studies.