bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding Roles of Accredited Social Health Activists (ASHAs) in the 2019 Hepatitis E Outbreak in a Peri-urban Slum, Nagpur, India
Authors: Selvaraj Kalaiselvi , Sujiv Akkilagunta , Banerjee Sitikantha , Bandyopadhyay Kajari , Deshmukh Pradeep Ramrao
Published: December 2022

Objective:

Due to constraints in the dedicated health work force, outbreaks in peri-urban slums are often reported late. This study explores the feasibility of deploying Accredited Social Health Activists (ASHAs) in outbreak investigation and understand the extent to which this activity gives a balanced platform to fulfil their roles during public health emergencies to reduce its impact and improve mitigation measures.

Methods:

Activities of ASHAs involved in the hepatitis E outbreak were reviewed from various registers maintained at the subcenter. Also, various challenges perceived by ASHAs were explored through focus group discussion (FGD). During March to May 2019, 13 ASHAs involved in the hepatitis outbreak investigation and control efforts in a peri-urban slum of Nagpur with population of around 9000. In total, 192 suspected hepatitis E cases reported.

Results:

During the outbreak, ASHAs performed multiple roles comprising house-to-house search of suspected cases, escorting suspects to confirm diagnosis and referral, community mobilization for out-reach investigation camps, risk communication to vulnerable, etc. During the activity, ASHAs faced challenges such as constraints in the logistics, compromise in other health-related activities, and challenges in sustaining behavior of the community.

Conclusions:

It is feasible to implement the investigation of outbreaks through ASHAs. Despite challenges, they are willing to participate in these activities as it gave them an opportunity to fulfil the role as an activist, link worker, as well as a community interface.
Short mid-infrared watt-level all-fiber nonlinear pulse compressor above 100-MHz pulse repetition rate
Authors: Shang Jingcheng , Mei Chao , Zhao Shengzhi , Liu Yizhou , Yang Kejian , Wang Chun , Li Tao , Feng Tianli
Published: December 2022

We firstly report a 2-μm all-fiber nonlinear pulse compressor based on two pieces of normal dispersion fiber (NDF), which enables a high-power scaling ability of watt-level and a high pulse compression ratio of 13.7. With the NDF-based all-fiber nonlinear pulse compressor, the 450-fs laser pulses with a repetition rate of 101.4 MHz are compressed to 35.1 fs, corresponding to a 5.2 optical oscillation cycle at the 2-μm wavelength region. The output average power reaches 1.28 W, which is believed to be the highest value never achieved from the previous 2-μm all-fiber nonlinear pulse compressors with a high pulse repetition rate above 100 MHz. The dynamic evolution of the ultrafast pulse inside the all-fiber nonlinear pulse compressor is numerically analyzed, matching well with the experimental results.
Flow-induced vibrations of a cylinder along a circular arc
Authors: Bourguet Rémi
Published: December 2022

An elastically mounted circular cylinder, immersed in a cross-current and free to move along a rectilinear path, is subjected to vortex-induced vibrations (VIV). These vibrations develop through a mechanism referred to as lock-in, where body motion and vortex shedding synchronize at a frequency that may deviate both from the oscillator natural frequency and from the vortex shedding frequency past a fixed cylinder. The present numerical study aims at extending the analysis to curved trajectories, by considering that the cylinder is free to translate along a circular path. The Reynolds number based on the body diameter (

$D$

) and current velocity (

$U$

) is set to

$100$

. A wide range of path radii, from

$0.05D$

to

$10D$

, and values of the reduced velocity (inverse of the oscillator natural frequency non-dimensionalized by

$D$

and

$U$

) up to

$30$

are examined, for the concave and convex configurations, i.e. the circular path centre located upstream or downstream of the cylinder. Path curvature results in a major alteration of the flow–body system behaviour compared with rectilinear VIV, with substantially different evolutions in the concave and convex configurations. In addition to the typical lock-in mechanism, two subharmonic forms of synchronization, at half and one third of vortex formation frequency, are uncovered in the convex configuration. They coexist with a desynchronized regime where the body and the flow oscillate at incommensurable frequencies. The four interaction regimes exhibit contrasted trends in terms of structural response, spatiotemporal organization of the wake and associated forces. They particularly differ by their symmetry properties, which are closely linked to the possible reconfiguration of the oscillator due to mean fluid forcing.
Getting by in a bibliometric economy: scholarly publishing and academic credibility in the Nigerian academy
Authors: Mills David , Branford Abigail
Published: December 2022

Why are Nigeria’s universities launching a growing number of open access journals while simultaneously expecting their academic staff to publish ‘internationally’? And what impact do these expectations have on Nigerian journals? Drawing on interviews with editors and publishers, we describe the emergence of a hyperlocal ‘credibility economy’ within the Nigerian academy. The great majority of Nigerian scholarly journals are excluded from Scopus and Web of Science, the two main global citation indexes. Stigmatized by geography, Nigerian journals are ignored, rendered invisible, classed as poor quality or condemned as ‘predatory’. Historicizing these trends, we illustrate our argument with four case studies: two science and technology journals hosted by universities and two independent publishers, one with expertise in African studies, the other in information studies. In each case, we explore the motivations, commitments and strategies of editors and publishers. Their stories exemplify the impact of colonial histories, global discourses and bibliometric infrastructures on African research publishing cultures. The histories, logics and fragilities of this regional research ecosystem reveal how Africa’s scholars and publishers are getting by – but only just – amid the metricized judgements of the global research economy.
Evaluation of bioelectrical impedance analysis in measuring body fat in 6-to-12-year-old boys compared with air displacement plethysmography
Authors: Mahaffey Ryan , Brown Nicola , Cramp Mary , Morrison Stewart C. , Drechsler Wendy I.
Published: December 2022

Air displacement plethysmography (ADP) has been considered as the ‘standard’ method to determine body fat in children due to superior validity and reliability compared with bioelectrical impedance analysis (BIA). However, ADP and BIA are often used interchangeably despite few studies comparing measures of percentage body fat by ADP (%FMADP) with BIA (%FMBIA) in children with and without obesity. The objective of this study was to measure concurrent validity and reliability of %FMADP and %FMBIA in 6-to-12-year-old boys with and without obesity. Seventy-one boys (twenty-five with obesity) underwent body composition assessment. Ten boys participated in intra-day reliability analysis. %FMADP was estimated by Bodpod using sex- and age-specific equations of body density. %FMBIA was estimated by a multi-frequency, hand-to-foot device using child-specific equations based on impedance. Validity was assessed by t tests, correlation coefficients and limits of agreement (LoA); and reliability by technical error of measurement (TEM) and intraclass correlation coefficients (ICC). Compared with %FMADP, %FMBIA was significantly underestimated in the cohort (–3·4 ± 5·6 %; effect size = 0·42) and in both boys with obesity (–5·2 ± 5·5 %; ES = 0·90) and without obesity (–2·4 ± 5·5 %; ES = 0·52). A strong, significant positive correlation was found between %FMADP and %FMBIA (r = 0·80). Across the cohort, LoA were 22·3 %, and no proportional bias was detected. For reliability, TEM were 0·65 % and 0·55 %, and ICC were 0·93 and 0·95 for %FMBIA and %FMADP, respectively. Whilst both %FMADP and %FMBIA are highly reliable methods, considerable differences indicated that the devices cannot be used interchangeably in boys age 6-to-12 years.
OP51 Improving Childhood Cancer Management And Financing In Ghana: Results From Stakeholder Mapping and Analysis
Authors: Owusu Richmond , Heupink Lieke Fleur , Gulbi Godwin , Asare Brian , Nonvignon Justice , Chola Lumbwe
Published: December 2022

Introduction

Coverage of childhood cancer treatment under the Ghanaian National Health Insurance Scheme (NHIS) has been a policy discussion recently. To improve priority setting, Ghana introduced and used health technology assessment (HTA) processes to guide the resource allocation. To understand the role of stakeholders throughout the HTA lifecycle and for this decision, a stakeholder mapping and engagement was undertaken. We share our results of this mapping and analysis for improving management and financing of childhood cancers in Ghana.

Methods

We used two main approaches; first, we undertook a systematic policy documents and literature review of stakeholders relevant in childhood cancer management and financing in Ghana. This was followed by a stakeholder engagement workshop of key stakeholders from the Ministry of Health, Ghana Health Service (GHS), National Health Insurance Authority (NHIA), academia, non-governmental organizations (NGOs), private sector, teaching hospitals, patient groups, and civil society organizations. Participation was done in-person and virtual. Questions were moderated using a focus group discussion approach where responses were recorded. Data were analysed using synthesis and development of themes. Mapping of stakeholders was done using Mendelow’s power-interest grid.

Results

The mapping identified eight key stakeholders in different roles: policy makers (Ministry of Health), payer (NHIA), healthcare providers (teaching hospitals, GHS, private hospitals), pharmaceutical companies, patient group (Ghana Parents Association for Childhood Cancers), and advocacy group (NGOs). Analysis showed that power and interest are concentrated with Ministry of Health and NHIA primarily because of control over resources. Also, while healthcare providers, patient groups, and advocacy groups have high interest, their power ranges from low to moderate. Further analysis of data from the workshop revealed that inability to pay for high cost of treatment leads to treatment abandonment. Payment for treatment was mainly out-of-pocket and by donation from philanthropist.

Conclusions

There was a strong will from stakeholders to extend coverage of the NHIS to childhood cancers in Ghana. Stakeholder engagement is a powerful tool and should be an integral part of every HTA process.
OP87 Value From A Multi-stakeholder Perspective: A Framework To Assess Digital Health Solutions For Improving Chronic Disease Management
Authors: Haig Madeleine , Main Caitlin , Chavez-Montoya Danitza , Kanavos Panos
Published: December 2022

Introduction

Innovative digital health technologies (DHTs) may present new aspects of value that are not appropriately accounted for in current health technology assessments. In discovering what value means in the context of DHTs, multi-stakeholder collaboration is essential.

Methods

A scoping literature review was conducted to identify current value assessment criteria and proposed methodologies across three health systems: United States of America, United Kingdom, and Germany. A Delphi exercise was conducted with stakeholders from the following groups: users, healthcare practitioners, decision-makers, supply-side actors, and influencers. Based on a review of assessment frameworks in the study countries and consultations with experts from each stakeholder group, researchers proposed value constructs in five domains: health inequalities, data rights and governance, technical and security, economic characteristics, clinical characteristics, and user preferences. In Delphi round one, participants commented on the proposed constructs and submitted their own. A thematic analysis identifying key concepts and themes of the participant proposed constructs and comments was used to incorporate this information for round two. Then, participants rated each value construct on an ‘importance’ Likert scale in two decision contexts: user-facing DHTs and system-facing DHTs. In round three, participants were presented with the consensus judgement for each construct, with the opportunity to change their answer. Value constructs with equal to or greater than 70 percent consensus were included in the final framework. Rounds four and five were, respectively, value judgements on a Likert scale and a presentation of consensus for a therapeutic area to test the final framework.

Results

Initially 32 value constructs were proposed by researchers, 20 of which were changed or removed based on round one feedback. Additional constructs were added based on participant suggestions resulting in forty-five value constructs in round two. The final framework will be available after round three closes on 20 December 2022.

Conclusions

The multi-stakeholder Delphi approach ensures that all suggestions and value judgements are weighted equally across stakeholder groups. The resultant value framework can be used to inform policymaking around health technology assessment of DHTs.
PD20 Real-World Evidence To Support Single Arm Trials Of Oncology Interventions: Necessity or ‘NICE’ (National Institute for Health and Care Excellence) to Have?
Authors: Falla Edel , Gaultney Jennifer
Published: December 2022

Introduction

The recent National Institute for Health and Care Excellence (NICE) consultation on methods for health technology evaluation (HTE) outlined plans to include guidance on the role of real-world evidence (RWE) in HTE. This is particularly pertinent for interventions where the evidence base consists of a single arm trial (SAT) design, which is more frequently observed in oncology. This study reviewed the influence of RWE submitted as part of the evidence base for NICE oncology appraisals.

Methods

A search for NICE HTEs was conducted for interventions supported by SATs from January 2017-November 2021. Evidence was stratified by submission packages with SAT evidence alone or in combination with randomized controlled trial (RCT) evidence, with or without RWE.

Results

Thirty-two decisions for interventions supported by SATs were made by NICE between 2017-2021, all in oncology indications. Fifty percent were supported by SAT evidence and fifty percent by RCT plus SAT evidence, both with or without RWE. A lower proportion of RCT/ SAT HTEs submitted RWE compared to SAT HTEs (fifty vs ninety four percent). Seventy five percent and nineteen percent of SAT HTEs received a positive recommendation, with and without restrictions, irrespective of submitting RWE. One negative decision was observed for SATs supported by RWE. Sixty three percent and thirty eight percent of RCT/ SAT HTEs received a positive recommendation, with and without restrictions. Overall, the proportion of positive recommendations were lower for HTEs submitting RWE (ninety six percent) compared to HTEs not submitting RWE (one hundred percent), which is in contrast to recent findings specific to orphan oncology HTEs (one hundred versus seventy eight percent).

Conclusions

RWE was more commonly submitted to support SAT HTEs, than RCT HTEs. The use of RWE seems to be established as a necessity to supplement a SAT evidence base, whereas RWE is more generally a nice to have in RCT HTEs. However, RWE appears to positively influence decision-making for orphan oncology indications with a more neutral influence for non-orphan indications.
The Impacts of the Covid-19 Pandemic and Lockdown Policies on Young Fathers: Comparative Insights from the UK and Sweden
Authors: Tarrant Anna , Ladlow Linzi , Johansson Thomas , Andreasson Jesper , Way Laura
Published: December 2022

This article explores the impacts of the first wave of the COVID-19 pandemic and lockdown policies on young fathers and their families. We present analyses from a larger programme of qualitative longitudinal research examining young fatherhood in the UK and Sweden to develop a unique international comparative and empirical contribution. The views and experiences of young fathers are examined in the context of two ostensibly different policy approaches during the pandemic. Organised thematically to enable comparison, our findings demonstrate myriad impacts, illustrating heightened precarity in young fathers’ transitions into and through fatherhood linked to restrictions on their engagement and changes to their education and employment trajectories and relational contexts, especially in the UK. We observe how differences in policy approaches before and during the first wave of the pandemic shaped the experiences of young fathers in the respective countries.
Existential distress and meaning making among female breast cancer patients with cancer-related fertility concerns
Authors: Carr Alaina L. , Roberts Sydneyjane , Bonnell Levi N. , Kolva Elissa
Published: December 2022

Objectives

The current study explored the impact of cancer-related fertility concerns on existential distress and meaning making among female breast cancer (BC) patients of childbearing age and assessed support needs.

Methods

The current study was embedded within a larger study. A seven-question online survey was administered to female BC participants to explore meaning and identity in their lives. Applied thematic analysis was used to analyze participants’ written responses.

Results

A total of 98 participants completed the survey, the majority of whom identified as white, married or partnered, and employed full time and with stage I or II BC. More than 50% of the participants expressed a need for support from a counselor or support group during their cancer experience. Three subthemes emerged related to existential distress and cancer-related fertility concerns: (1) loss of womanhood: treatment-related physical changes impact on gender identity; (2) existential distress due to treatment decisions impacting fertility; and (3) shattered vision: cancer-related infertility impact on meaning and purpose. Four subthemes emerged related to meaning making with fertility-related existential concerns: (1) coping with loss of meaning, (2) re-evaluating priorities in life; (3) resilience to loss, and (4) persistent loss of meaning.

Significance of Results

Study results offer valuable insights into the experiences of female BC survivors’ cancer-related fertility on existential distress and meaning making. Development of psychological interventions targeted to support this population to cope with existential distress due to cancer-related fertility concerns and meaning making are needed to improve the quality of life of this population.
Time for religion? Liberalism, Haredi Jews, and state regulation of nonpublic schools
Authors: Tampio Nicholas
Published: December 2022

Political theorists argue that justice requires treating people's time as having equal worth. In this article, I contend that justice sometimes requires making exceptions to uniform time rules. The article focuses on New York State's regulations for nonpublic schools and how they affect Haredi (ultra-Orthodox) Jewish day schools, or yeshivas. Dissatisfied yeshiva graduates, the state education department, and several liberal political theorists assert that the state should pressure yeshivas to dedicate more time to secular studies. Reconstructing Horace Kallen's argument against the melting pot conception of citizenship and for cultural pluralism, I maintain that liberal states should be generous toward non-liberal ways of life on condition that they do not systematically abuse children or pose a danger to public safety. A liberal education landscape may sustain many kinds of schooling, including ones that outsiders think waste time.
Determining how almond (Prunus dulcis) harvest and processing contributes to low levels of glyphosate and glufosinate residues in almonds
Authors: Martin Katie , Hanson Bradley D.
Published: December 2022

California is the top producer of almonds [Prunus dulcis (Mill.) D.A. Webb] worldwide, generating more than $6 billion in revenue in 2020; the European Union (EU) is the primary importer of California almonds. Weed control in almond orchards is an important part of the preharvest process, because weeds can interfere with harvest equipment and host diseases. Glyphosate and glufosinate are broad-spectrum herbicides commonly used for preharvest weed control. Global differences in maximum residue limits (MRLs) and regulated compounds can pose a challenge for growers who rely on broad-spectrum herbicides such as glyphosate and glufosinate for preharvest weed control. The EU MRL for glyphosate and total glufosinate is currently 0.1 mg kg−1. The U.S. MRL for total glyphosate is 1 mg kg−1, and total glufosinate is 0.5 mg kg−1. An 8-wk field experiment, from spray to harvest, was conducted in an 8-ha commercial orchard to evaluate the potential contribution of the preharvest herbicide treatment to low levels of herbicide residue in almonds. Then, the same batch of almonds was followed through a commercial processing facility to evaluate the potential movement of herbicide residues from soil, debris, and hulls to almond kernels during processing. Glyphosate was not detected in any almond kernel samples at the end of processing. A glufosinate metabolite, 3-(methylphosphinico)propionic acid (MPP), was detected in kernels at the end of processing at about 0.1 mg kg−1, which is above the EU MRL for total glufosinate. Almonds sampled directly from the tree, without any contact with soil, were found to have elevated MPP residues. This indicates glufosinate or MPP translocation may be a factor in low-level glufosinate residues detected in almonds in some EU exports.
Model‐Free Approach for Regional Ionospheric Multi‐Instrument Imaging
Authors: Norberg J. , Käki S. , Roininen L. , Mielich J. , Virtanen I. I.
Published: December 2022

The article proposes a straightforward Kalman filter‐based method for computationally efficient ionospheric electron density multi‐instrument imaging. The approach uses direct ionospheric measurements, such as ionosondes, and general physical assumptions to estimate the uncertainty associated with the previous reconstructed time step. Therefore the method does not require any electron density model of the ionosphere as a background. The uncertainty is represented by an inverse covariance matrix constructed with Gaussian Markov random fields, allowing the problem to be solved directly with relatively high resolution. The experiments utilize measurements from dense ground‐based GNSS and low Earth orbit beacon satellite receiver networks as well as ionosondes. A synthetic simulation verification and real data validation with a specific European Incoherent Scatter Scientific Association incoherent scatter radar measurement campaign is carried out over Northern European sector. The method can be controlled using parameters with probabilistic and physically realistic interpretations that can be applied to both simulated and real‐world data. The results show that the approach is feasible for near real‐time regional ionospheric imaging. Especially, the method can be seen as an expansion to local profile measurements field of view, but with sufficient measurement coverage, it also provides information further away from the specific instrument.
Consistency of Seasonal Mean and Extreme Precipitation Projections Over Europe Across a Range of Climate Model Ensembles
Authors: Ritzhaupt N. , Maraun D.
Published: December 2022

Uncertainties of regional precipitation projections are substantial, and users of such projections face the so‐called practitioners dilemma: a plethora of projections with different models from different ensembles of different types and generations are available. But the consistency of these projections has not been systematically assessed, such that no clear guidance about the use of these ensembles exists. Therefore, we systematically compare, separately for each season, projections of mean precipitation and extremes of daily precipitation over Europe across a wide range of climate model ensembles. We specifically consider the global climate model ensembles CMIP3, CMIP5, Coupled Model Intercomparison Project Phase 6 (CMIP6), and HighresMIP as well as the regional climate model ensembles ENSEMBLES and EURO‐CORDEX. All considered ensembles agree in their large‐scale patterns of changes for both mean and extreme daily precipitation, but at the regional scale, substantial discrepancies and inconsistencies are evident. Within and across ensemble spread is strongest in summer, in particular for the drying trend over the Mediterranean and Eastern Europe. CMIP5 and CMIP6 are broadly consistent. The regional climate model (RCM) ensembles modify the signals of the driving global climate models indicating potential added value. The high resolution of the RCM and HighresMIP ensembles seems to be key over the Alps for summer precipitation. Our study provides important information for users of climate projections as it helps to establish continuity across generations and types of climate models, and aids the design of new climate impact studies.
Classification and Semiquantitative Evaluation of Paleoearthquake Identification From Trenches on Normal Faults: A Case Study of Holocene Paleoearthquake Events From the Northern Margin of the Hetao Basin, China
Authors: Xu Dongsheng , He Zhongtai , Ma Baoqi , Liang Kuan , Long Jianyu , Zhang Hao
Published: December 2022

Long paleoearthquake series are crucial for understanding the recurrence patterns of active faults and evaluating the seismic hazards of faults. In this study, the first semiquantitative evaluation of paleoearthquake events from trenches was applied to normal faults, and classification criteria for identifying paleoearthquakes in trenches on normal faults are proposed to demonstrate the feasibility of semiquantitative evaluations of paleoearthquake events on normal faults. In this study, 72 paleoearthquake trench sites on normal faults around the world were analyzed, and the main indicators for identifying paleoearthquakes on normal faults include the presence of vertical offset (VO), collapse wedge (CW), fissure (FIS), buried paleosol (BP), angular unconformity (AU), upward termination (UT), and sand liquefaction (LF) features. To describe and apply this semiquantitative evaluation method for paleoearthquake events on normal faults, 33 trenches for paleoearthquakes on a fault system in the northern margin of the Hetao Basin were comprehensively analyzed to determine Holocene paleoearthquake events on the Sertengshan, Wulashan, and Daqingshan piedmont faults, and the reliability of paleoearthquake events is discussed. The integrity of the paleoearthquake events obtained was tested by the displacement limit method. The Holocene paleoearthquake recurrence on the three faults was quasiperiodic; the coefficients of variation (COVs) were 0.44, 0.58, and 0.4.
Characterizing the Three‐Dimensional Flow in Partially Vegetated Channels
Authors: Unigarro Villota S. , Ghisalberti M. , Philip J. , Branson P.
Published: December 2022

Partially obstructed shear flows, such as flows over submerged vegetation patches in river systems, are common in natural environments. Here, a model of a patchily‐vegetated river flow, using staggered arrays of rigid wooden dowels, is used to experimentally characterize the flow. Three‐component point velocity measurements in the cross sectional plane are used to investigate the highly nonuniform, 3D flow field in patchy vegetation and its effect on mass and momentum exchange. The cross‐sectional distribution of mean streamwise velocity varies as a consequence of the bed heterogeneity, being highly dependent on vegetation density. Asymmetric shear layers form at the vertical and lateral edges of the canopy, having different scales within the canopy and in the unvegetated region. Secondary flow cells form in the cross‐plane, with a size that decreases with increasing canopy density. The strength of the upward and downward motions is found to be greater for denser canopies. In addition to the secondary flow, additional rotating cells are observed both above the patch and next to it with increasing canopy density. A triple‐averaging procedure allowed for the quantification of the vertical advective dispersive stresses, which are up to 21% of the total shear stress. This demonstrates the significant role of secondary circulation generated by patchy vegetation in interfacial momentum exchange. Finally, the secondary circulation contribution to vertical scalar transport is estimated to be of the same order as that due to turbulent diffusion, highlighting the importance of understanding the impact of the secondary flow field on aquatic ecosystem function.
Switch mode capacitive pressure sensors
Authors: Shalabi Nabil , Searles Kyle , Takahata Kenichi
Published: December 2022

Switch mode capacitive pressure sensors are proposed as a new class of microfabricated devices that transform pressure into a mechanically switching capacitance to form an analog-to-digital signal with zero power, high sensitivity, and a high signal-to-noise ratio. A pressure-sensitive gold membrane suspended over a capacitive cavity makes ohmic contact with patterned gold leads on the substrate, closing circuits to fixed on-chip capacitors outside the cavity and leading to significant step responses. This function is achieved by allocating the switch leads on the part of the counter electrode area, while the remaining area is used for touch mode analog capacitive sensing. The sensor microchip is prototyped through a novel design approach to surface micromachining that integrates micro-Tesla valves for vacuum sealing the sensor cavity, showing an unprecedented response to applied pressure. For a gauge pressure range of 0–120 mmHg, the sensor exhibits an increase of 13.21 pF with resultant switch events, each of which ranges from 2.53–3.96 pF every 12–38 mmHg, in addition to the touch mode linear capacitive increase between switches. The equivalent sensitivity is 80–240 fF/mmHg, which is 11–600× more than commercial and reported touch mode sensors operating in similar pressure ranges. The sensor is further demonstrated for wireless pressure tracking by creating a resonant tank with the sensor, showing a 32.5–101.6 kHz/mmHg sensitivity with frequency jumps led by the switch events. The developed sensor, with its promising performance, offers new application opportunities in a variety of device areas, including health care, robotics, industrial control, and environmental monitoring.
The sodium channel subunit SCNN1B suppresses colorectal cancer via suppression of active c-Raf and MAPK signaling cascade
Authors: Qian Yun , Zhou Lianxin , Luk Simson Tsz Yat , Xu Jiaying , Li Weilin , Gou Hongyan , Chen Huarong , Kang Wei , Yu Jun , Wong Chi Chun
Published: December 2022

The incidence of colorectal cancer (CRC) is rising worldwide. Here, we identified SCNN1B as an outlier down-regulated in CRC and it functions as a tumor suppressor. SCNN1B mRNA and protein expression were down-regulated in primary CRC and CRC cells. In a tissue microarray cohort (N = 153), SCNN1B protein was an independent prognostic factor for favorable outcomes in CRC. Ectopic expression of SCNN1B in CRC cell lines suppressed cell proliferation, induced apoptosis, and cell cycle arrest, and suppressed cell migration in vitro. Xenograft models validated tumor suppressive function of SCNN1B in vivo. Mechanistically, Gene Set Enrichment Analysis (GSEA) showed that SCNN1B correlates with KRAS signaling. Consistently, MAPK qPCR and kinase arrays revealed that SCNN1B suppressed MAPK signaling. In particular, SCNN1B overexpression suppressed p-MEK/p-ERK expression and SRE-mediated transcription activities, confirming blockade of Ras-Raf-MEK-ERK cascade. Mechanistically, SCNN1B did not affect KRAS activation, instead impairing activation of c-Raf by inducing its inhibitory phosphorylation and targeting active c-Raf for degradation. The ectopic expression of c-Raf fully rescued cell proliferation and colony formation in SCNN1B-overexpressing CRC cells, confirming c-Raf as the principal molecular target of SCNN1B. In summary, we identified SCNN1B as a tumor suppressor by functioning as a c-Raf antagonist, which in turn suppressed oncogenic MEK-ERK signaling.
ATX-101, a cell-penetrating protein targeting PCNA, can be safely administered as intravenous infusion in patients and shows clinical activity in a Phase 1 study
Authors: Lemech Charlotte Rose , Kichenadasse Ganessan , Marschner Jens-Peter , Alevizopoulos Konstantinos , Otterlei Marit , Millward Michael
Published: December 2022

Proliferating Cell Nuclear Antigen (PCNA) is a highly conserved protein essential for DNA replication, repair and scaffold functions in the cytosol. Specific inhibition of PCNA in cancer cells is an attractive anti-cancer strategy. ATX-101 is a first-in-class drug targeting PCNA, primarily in cellular stress regulation. Multiple in vivo and in vitro investigations demonstrated anti-cancer activity of ATX-101 in many tumor types and a potentiating effect on the activity of anti-cancer therapies. Healthy cells were less affected. Based on preclinical data, a clinical phase 1 study was initiated. Twenty-five patients with progressive, late-stage solid tumors were treated with weekly ATX-101 infusions at four dose levels (20, 30, 45, 60 mg/m2). ATX-101 showed a favorable safety profile supporting that vital cellular functions are not compromised in healthy cells. Mild and moderate infusion-related reactions were observed in 64% of patients. ATX-101 was quickly cleared from blood with elimination half-lives of less than 30 min at all dose levels, probably due to both, a quick cell penetration and peptide digestion in serum, as demonstrated in vivo. No tumor responses were observed but stable disease was seen in 70% of the efficacy population (n = 20). Further studies have been initiated to provide evidence of efficacy. Trial registration numbers: ANZCTR 375262 and ANZCTR 375319.
All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits
Authors: Wu Huai-liang , Luo Zi-yin , He Zong-lin , Gong Yue , Mo Miao , Ming Wai-kit , Liu Guang-yu
Published: December 2022

Background

The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA).

Methods

We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2.

Results

Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively.

Discussion

By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.
Challenges for the implementation of next generation sequencing-based expanded carrier screening: Lessons learned from the ciliopathies
Authors: Vintschger Ella , Kraemer Dennis , Joset Pascal , Horn Anselm H. C. , Rauch Anita , Sticht Heinrich , Bachmann-Gagescu Ruxandra
Published: December 2022

Next generation sequencing (NGS) can detect carrier status for rare recessive disorders, informing couples about their reproductive risk. The recent ACMG recommendations support offering NGS-based carrier screening (NGS-CS) in an ethnic and population-neutral manner for all genes that have a carrier frequency >1/200 (based on GnomAD). To evaluate current challenges for NGS-CS, we focused on the ciliopathies, a well-studied group of rare recessive disorders. We analyzed 118 ciliopathy genes by whole exome sequencing in ~400 healthy local individuals and ~1000 individuals from the UK1958-birth cohort. We found 20% of healthy individuals (1% of couples) to be carriers of reportable variants in a ciliopathy gene, while 50% (4% of couples) carry variants of uncertain significance (VUS). This large proportion of VUS is partly explained by the limited utility of the ACMG/AMP variant-interpretation criteria in healthy individuals, where phenotypic match or segregation criteria cannot be used. Most missense variants are thus classified as VUS and not reported, which reduces the negative predictive value of the screening test. We show how gene-specific variation patterns and structural protein information can help prioritize variants most likely to be disease-causing, for (future) functional assays. Even when considering only strictly pathogenic variants, the observed carrier frequency is substantially higher than expected based on estimated disease prevalence, challenging the 1/200 carrier frequency cut-off proposed for choice of genes to screen. Given the challenges linked to variant interpretation in healthy individuals and the uncertainties about true carrier frequencies, genetic counseling must clearly disclose these limitations of NGS-CS.
Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy
Authors: Luppe Johannes , Sticht Heinrich , Lecoquierre François , Goldenberg Alice , Gorman Kathleen M. , Molloy Ben , Agolini Emanuele , Novelli Antonio , Briuglia Silvana , Kuismin Outi , Marcelis Carlo , Vitobello Antonio , Denommé-Pichon Anne-Sophie , Julia Sophie , Lemke Johannes R. , Abou Jamra Rami , Platzer Konrad
Published: December 2022

The neuronal SNARE complex drives synaptic vesicle exocytosis. Therefore, one of its core proteins syntaxin 1A (STX1A) has long been suspected to play a role in neurodevelopmental disorders. We assembled eight individuals harboring ultra rare variants inSTX1Awho present with a spectrum of intellectual disability, autism and epilepsy. Causative variants comprise a homozygous splice variant, three de novo missense variants and two inframe deletions of a single amino acid. We observed a phenotype mainly driven by epilepsy in the individuals with missense variants in contrast to intellectual disability and autistic behavior in individuals with single amino acid deletions and the splicing variant. In silico modeling of missense variants and single amino acid deletions show different impaired protein-protein interactions. We hypothesize the two phenotypic courses of affected individuals to be dependent on two different pathogenic mechanisms: (1) a weakened inhibitory STX1A-STXBP1 interaction due to missense variants results in anSTX1A-related developmental epileptic encephalopathy and (2) a hampered SNARE complex formation due to inframe deletions causes anSTX1A-related intellectual disability and autism phenotype. Our description of aSTX1A-related neurodevelopmental disorder with or without epilepsy thus expands the group of rare diseases called SNAREopathies.
Self-powered high-sensitivity all-in-one vertical tribo-transistor device for multi-sensing-memory-computing
Authors: Liu Yaqian , Liu Di , Gao Changsong , Zhang Xianghong , Yu Rengjian , Wang Xiumei , Li Enlong , Hu Yuanyuan , Guo Tailiang , Chen Huipeng
Published: December 2022

Devices with sensing-memory-computing capability for the detection, recognition and memorization of real time sensory information could simplify data conversion, transmission, storage, and operations between different blocks in conventional chips, which are invaluable and sought-after to offer critical benefits of accomplishing diverse functions, simple design, and efficient computing simultaneously in the internet of things (IOT) era. Here, we develop a self-powered vertical tribo-transistor (VTT) based on MXenes for multi-sensing-memory-computing function and multi-task emotion recognition, which integrates triboelectric nanogenerator (TENG) and transistor in a single device with the simple configuration of vertical organic field effect transistor (VOFET). The tribo-potential is found to be able to tune ionic migration in insulating layer and Schottky barrier height at the MXene/semiconductor interface, and thus modulate the conductive channel between MXene and drain electrode. Meanwhile, the sensing sensitivity can be significantly improved by 711 times over the single TENG device, and the VTT exhibits excellent multi-sensing-memory-computing function. Importantly, based on this function, the multi-sensing integration and multi-model emotion recognition are constructed, which improves the emotion recognition accuracy up to 94.05% with reliability. This simple structure and self-powered VTT device exhibits high sensitivity, high efficiency and high accuracy, which provides application prospects in future human-mechanical interaction, IOT and high-level intelligence.
Dual fluorination of polymer electrolyte and conversion-type cathode for high-capacity all-solid-state lithium metal batteries
Authors: Hu Jiulin , Lai Chuanzhong , Chen Keyi , Wu Qingping , Gu Yuping , Wu Chenglong , Li Chilin
Published: December 2022

All-solid-state batteries are appealing electrochemical energy storage devices because of their high energy content and safety. However, their practical development is hindered by inadequate cycling performances due to poor reaction reversibility, electrolyte thickening and electrode passivation. Here, to circumvent these issues, we propose a fluorination strategy for the positive electrode and solid polymeric electrolyte. We develop thin laminated all-solid-state Li||FeF3 lab-scale cells capable of delivering an initial specific discharge capacity of about 600 mAh/g at 700 mA/g and a final capacity of about 200 mAh/g after 900 cycles at 60 °C. We demonstrate that the polymer electrolyte containing AlF3 particles enables a Li-ion transference number of 0.67 at 60 °C. The fluorinated polymeric solid electrolyte favours the formation of ionically conductive components in the Li metal electrode’s solid electrolyte interphase, also hindering dendritic growth. Furthermore, the F-rich solid electrolyte facilitates the Li-ion storage reversibility of the FeF3-based positive electrode and decreases the interfacial resistances and polarizations at both electrodes.
Economic and biophysical limits to seaweed farming for climate change mitigation
Authors: DeAngelo Julianne , Saenz Benjamin T. , Arzeno-Soltero Isabella B. , Frieder Christina A. , Long Matthew C. , Hamman Joseph , Davis Kristen A. , Davis Steven J.
Published: December 2022

Net-zero greenhouse gas (GHG) emissions targets are driving interest in opportunities for biomass-based negative emissions and bioenergy, including from marine sources such as seaweed. Yet the biophysical and economic limits to farming seaweed at scales relevant to the global carbon budget have not been assessed in detail. We use coupled seaweed growth and technoeconomic models to estimate the costs of global seaweed production and related climate benefits, systematically testing the relative importance of model parameters. Under our most optimistic assumptions, sinking farmed seaweed to the deep sea to sequester a gigaton of CO2 per year costs as little as US$480 per tCO2 on average, while using farmed seaweed for products that avoid a gigaton of CO2-equivalent GHG emissions annually could return a profit of $50 per tCO2-eq. However, these costs depend on low farming costs, high seaweed yields, and assumptions that almost all carbon in seaweed is removed from the atmosphere (that is, competition between phytoplankton and seaweed is negligible) and that seaweed products can displace products with substantial embodied non-CO2 GHG emissions. Moreover, the gigaton-scale climate benefits we model would require farming very large areas (>90,000 km2)—a >30-fold increase in the area currently farmed. Our results therefore suggest that seaweed-based climate benefits may be feasible, but targeted research and demonstrations are needed to further reduce economic and biophysical uncertainties.
Accelerating tobacco control at the national level with the Smoke-free Generation movement in the Netherlands
Authors: Willemsen Marc C. , Been Jasper V.
Published: December 2022

The Netherlands has moved towards the forefront of tobacco control in Europe, after having implemented important tobacco control measures in 2020 and 2021, which included higher tobacco taxation, plain packaging of tobacco products, a partial point of sale tobacco display ban, smoking ban on school grounds, and other smoking restrictions. We examined the factors contributing to these successes, focussing on the network of tobacco control advocacy organisations and the process of agenda-setting. Crucial determining factors were stricter adherence to Article 5.3 FCTC, which prevents government to consult tobacco industry, and the genesis of a ‘Smoke-free Generation’ movement in the wider society, initiated by the three main national charities (Lung Foundation Netherlands, Dutch Heart Foundation, Dutch Cancer Society). The Smoke-free Generation concept proved to be a highly attractive unifying strategy for national en local policy makers and Dutch society. As a result, the Dutch government was able to start a process of strengthening tobacco control policy through drafting and implementing a National Prevention Agreement, which aims at a tobacco control endgame goal of less than 5% smokers in 2040. Between 2019 and 2020 smoking rates dropped from 21.7% to 20.2%. The Dutch experience can provide inspiration for countries where tobacco control is still lagging behind. It also illustrates that continued vigilance is needed, since the most recent government change was associated with a hampering of further reduction of the proportion of smokers and a temporary drop in attention to tobacco control from the central government.