bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigations of methods for multiple time‐to‐event endpoints: A chronic myeloid leukemia data analysis
Authors: Wu Hongji , Hou Yawen , Chen Zheng
Published: August 2022

Background

In randomized controlled trials, multiple time‐to‐event endpoints are commonly used to determine treatment effects. However, choosing an appropriate method to address multiple endpoints, according to different purposes of clinical practice, is a challenge for researchers.

Methods

We applied single endpoint, composite endpoint and win ratio analysis to chronic myeloid leukemia (CML) data to illustrate the distinctions with different multiple endpoints, including relapse, recovery and death after transplantation.

Results

Regarding relapse and death, the hazard ratio in single endpoint analysis (HRs) were 1.281 (95% CI: 1.061−1.546) and hazard ratio in composite endpoint analysis (HRc) were 1.286 (95% CI: 1.112−1.486) and 1/WR (win ratio) was 1.292 (95% CI: 1.115−1.497) indicated a similar negative effect for non‐prophylaxis patients. However, when considering recovery and death, the corresponding HRs = 1.280 (95% CI: 1.056−1.552) may not be enough to describe the effect on death with nonproportional hazards (p < 0.05), and for the composite endpoint analysis, the HRc = 0.828 (95% CI: 0.740−0.926) cannot quantify and interpret the clinical effect on the composite endpoint with the combination of recovery and death, while the 1/WR = 1.351 (95% CI: 1.207−1.513) showed an unfavourable effect for non‐prophylaxis patients

Conclusions

When dealing with multiple endpoints, single endpoints, researchers may choose single endpoints, composite endpoints and WR analysis due to different clinical applications and purposes. However, both single and composite endpoint analyses are hazard‐based measures, and thus, the proportional hazards assumption should be considered. Moreover, composite endpoint analysis should be applied for endpoints with similar clinical meanings but not opposing implications. Win ratio analysis can be considered for different clinical importance of multiple endpoints, but the meaning of ‘winner’ needs to be specified for desired or undesired endpoints.
Novel image enhancement technology that helps find bleeding points during endoscopic submucosal dissection of gastric neoplasms
Authors: Funasaka Kohei , Miyahara Ryoji , Horiguchi Noriyuki , Omori Takafumi , Osaki Hayato , Yoshida Dai , Yamada Hyuga , Koyama Keishi , Nagasaka Mitsuo , Nakagawa Yoshiyuki , Hashimoto Senju , Shibata Tomoyuki , Hirooka Yoshiki
Published: August 2022

Background and Aim

The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology.

Methods

Eighteen video scenes of bleeding points from five gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point, and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE‐L*a*b* color space were calculated in the original and enhanced images.

Results

The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 s vs 13.85 s) (P = 0.017). On a 5‐point (−2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images was significantly larger than that on the original images (10.93 vs 8.36).

Conclusion

This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists.
Using waste to supply steam for industry transition: Selection of target industries through economic evaluation and statistical analysis
Authors: Maki Seiya , Ohnishi Satoshi , Fujii Minoru , Goto Naohiro , Sun Lu
Published: August 2022

Global warming mitigation requires worldwide action in a wide range of fields, including waste treatment and management. In Japan, demands to transform waste into energy as a greenhouse gas emissions reduction strategy are increasing. The use of steam generated from waste treatment plants as a source of energy in industries is a promising energy recovery method. In recent years, the feasibility and economic potential of conversion of waste into energy have been evaluated; however, economic efficiency is not always achieved. Therefore, it is necessary to classify steam supply targets based on profitability. Herein, we selected appropriate industries from different types and scales of industries for steam supply based on analyses carried out in Aichi Prefecture. Therefore, industries were classified based on their production shipment value. We also calculated the maximum profit potential from steam supply from waste treatment plants and the steam demand potential of each mesh. We applied data envelopment analysis (DEA) to evaluate energy efficiency and regression analysis to evaluate the potential effects on growth. The appropriate industry was estimated through decision tree analysis based on DEA scores for the mixed industries cluster. We extracted four appropriate industries: pulp, textiles, ceramics, and steel. For each industry, we calculated the number of firms required in the mesh for economic benefit. We also selected industries that could be used to explore the potential of adopting the developed methodology for other regions and industries and for identification of waste treatment plants that could participate in steam supply.
Impact of advance care planning and end‐of‐life conversations on patients with cancer: An integrative review of literature
Authors: Goswami Poonam
Published: August 2022

Purpose

The purpose was to review published articles to examine the impact of advance care planning (ACP) and end‐of‐life (EOL) conversations on patients with cancer, and aimed to compare the findings for congruency with the goals of ACP.

Design and Method

The study was guided by Whittemore and Knafl's integrative review methodology. Articles published between 2015 to 2020 were identified through electronic databases. The search included: Cumulative Index for Nursing Allied Health Literature (CINAHL), PubMed, MEDLINE‐Ovid, and MEDLINE full text, and using the MeSH terms. Two hundred and five (205) articles were identified and screened for eligibility, and 15 articles were appraised.

Findings

The fifteen (15) articles that met the inclusion criteria included five (5) qualitative, eight (8) quantitative, and two (2) mixed methods. The review analysis revealed six themes emerged in three categories: cancer patients' experience with advance care planning (1) patients' prognostic awareness, (2) decision making; cancer patients' perceived outcomes with advance care planning (3) patient‐provider relationship, (4) concordance in care based on goals, and cancer patients' propositions related to advance care planning, (5) timings of advance care planning discussions, and (6) support during ACP and/or EOL conversations.

Conclusion

ACP and EOL conversations play a critical role in cancer patients' awareness of their disease and prognosis and help them in making end‐of‐life care decisions.

Clinical relevance

There exists a need for earlier ACP and EOL conversations with cancer patients with emotional support during these conversations.
Meir Kahane and Race as Incarnational Theology
Authors: Heschel Susannah
Published: August 2022

The widespread receptivity of Jewish communities around the world to Meir Kahane demands that we reconsider our narrative of modern Jewish history and religious thought. His racism, calls for violence, and protofascism are startling, given the standard presentation that liberalism and assimilation mark the modern Jewish era. Even more startling is that Kahane's name almost never appears in the major surveys of American Judaism, the history of Zionism, and modern Jewish thought. Yet, Kahane's influence is growing rapidly and already outweighs the influence of most other modern Jewish thinkers and shows no sign of abating, especially with the rise of authoritarian regimes around the world.
School‐Based Health Center Utilization During COVID‐19 Pandemic‐Related School Closures
Authors: Gallardo Michelle , Zepeda Alex , Biely Christopher , Jackson Nicholas , Puffer Maryjane , Anton Patricia , Dudovitz Rebecca
Published: August 2022

Background

Little is known regarding utilization of school‐based health centers (SBHCs) during prolonged school closures, such as those that occurred during the COVID‐19 pandemic. We sought to compare SBHC utilization before and after pandemic‐related school closures across a network of SBHCs affiliated with a large Southern Californian urban school district.

Methods

We conducted a secondary analysis of encounter data extracted from electronic health records from 12 SBHCs that remained open despite school closures, including patient demographics and diagnostic and billing codes. We used the Clinical Classifications Software Refined to group encounters for common primary care conditions. Utilization before and during pandemic‐related school closures was compared using logistic regression with cluster‐robust standard errors to account for clustering within clinics, after adjusting for month of encounter.

Results

During the pandemic, study SBHCs conducted 52,530 encounters and maintained ∼4040 encounters/month. The frequency of encounters for annual preventative health exams increased for school‐aged patients but decreased for other age groups while the frequency of encounters for mental health problems increased for all age groups.

Implications for School Health Policy, Practice, and Equity

Despite pandemic‐related school closures, SBHCs appeared play a critical role in providing primary care to vulnerable communities.

Conclusions

SBHCs may hold value beyond their co‐location with academic instruction.
Contending philosophy of social science perspectives: A flexible typology
Authors: Buch‐Hansen Hubert
Published: August 2022

Philosophy of social science (PoS) typologies can help practitioners in the social sciences to reflect upon the often‐tacit assumptions embedded in research. Existing PoS typologies however suffer from various shortcomings, one of them being a tendency to present extreme versions of the assumptions underpinning research. Having considered this and other shortcomings, the present paper advances a flexible PoS typology. Operating with strong and moderated versions of three PoS perspectives – positivism, constructionism and (critical) realism – the typology captures key assumptions underpinning a broad range of contemporary social research. Moreover, it opens up the possibility of contemplating the assumptions embedded in research in a more fruitful way. To render tangible how the typology constitutes an improvement over existing typologies, it is used in reflections on sustainability research on climate negotiations, green growth and housing development.
Chloroplast redox state changes mark cell‐to‐cell signaling in the hypersensitive response
Authors: Lukan Tjaša , Županič Anže , Mahkovec Povalej Tjaša , Brunkard Jacob O. , Kmetič Mirjam , Juteršek Mojca , Baebler Špela , Gruden Kristina
Published: August 2022

Hypersensitive response (HR)‐conferred resistance is associated with induction of programmed cell death and pathogen spread restriction in its proximity. The exact role of chloroplastic reactive oxygen species and its link with salicylic acid (SA) signaling in HR remain unexplained.

To unravel this, we performed a detailed spatiotemporal analysis of chloroplast redox response in palisade mesophyll and upper epidermis to potato virus Y (PVY) infection in a resistant potato genotype and its transgenic counterpart with impaired SA accumulation and compromised resistance.

Besides the cells close to the cell death zone, we detected individual cells with oxidized chloroplasts further from the cell death zone. These are rare in SA‐deficient plants, suggesting their role in signaling for resistance. We confirmed that chloroplast redox changes play important roles in signaling for resistance, as blocking chloroplast redox changes affected spatial responses at the transcriptional level.

Through spatiotemporal study of stromule induction after PVY infection, we show that stromules are induced by cell death and also as a response to PVY multiplication at the front of infection. Overall induction of stromules is attenuated in SA‐deficient plants.
Dysphagia‐related mucositis in children undergoing chemotherapy: The COMEDY pattern
Authors: Bardellini Elena , Amadori Francesca , Veneri Federica , Albini Giorgia , Porta Fulvio , Alessandra Majorana
Published: August 2022

Objectives

Children undergoing chemotherapy can experience dysphagia due to non‐erosive reflux disease (NERD). Oral mucositis (OM) associated with NERD‐dysphagia in children with cancer has recently been defined with the acronym COMEDY (Clenching, Oral Mucositis, closed Eyes, DYsphagia). This study aims to identify the prevalence of the COMEDY pattern among chemotherapy‐induced OM.

Subjects and methods

Forty‐two medical records of children undergoing chemotherapy for haemato‐oncologic diseases and presenting OM were reviewed. The following data were collected: age, type of haemato‐oncologic disease, presence of dysphagia, type of oral mucosal lesions (i.e. traditional oral mucositis or COMEDY pattern), site of oral lesions, ear‐nose‐throat (ENT) assessment for the indirect signs of NERD and paediatric neuro‐psychiatric (PNP) assessment.

Results

Among 42 children with chemotherapy‐related OM, 6 patients (14.2%) showed the COMEDY pattern. Besides the characteristic clinical aspect of the oral mucosa, initially classified as grade II OM, these children suffered from NERD‐related dysphagia and PNP issues.

Conclusion

A COMEDY pattern can occur in a number of cases of chemotherapy‐induced OM; recognizing this pattern may improve the effectiveness of treatment.
Simultaneous Measurement of Patellofemoral Joint Kinematics and Contact Mechanics in Intact Knees: A Cadaveric Study
Authors: Huang Wenhan , Zeng Xiaolong , Man Gene Chi‐Wai , Yang Liu , Zhang Yu
Published: August 2022

Objective

Patellofemoral kinematics and contact mechanics are important measurements for the assessment of patellofemoral joint (PFJ) problems. Simultaneously measuring PFJ contact pressures and kinematics is a challenging task. The purpose of this study was to simultaneously measure the kinematics and mean/peak contact pressures in the PFJs of cadaveric knees.

Methods

This was a comparative study performed on fresh cadaveric knees. The kinematic data was acquired for nine cadaveric knees using an optical tracking system. Data about the contact pressure and contact area in the PFJ was obtained at knee flexion angles of 0°, 30°, 60°, 90°, and 120° using a pressure sensor. Intraclass correlation coefficients (ICCs) and minimal detectable differences (MDDs) of six degrees of freedom (6 DOF) in the PFJs were calculated. ICCs and the MDDs of contact pressure, peak pressure, and contact area in the PFJs were also analyzed. We also compared the kinematics of the cadaveric knees before and after the insertion of the pressure sensor.

Results

All ICC values of 6 DOF in the PFJs were found to be greater than or equal to 0.924. Regarding medial–lateral rotation, the patellar showed a simplified movement pattern that demonstrated progressive lateral rotation of 4.8° ± 3.4° at 120° of knee flexion. While for patellar tilting, the patella showed medial tilting that peaked at 7.2 ± 2.5° at 30° of knee flexion. Whereas no significant differences in PFJ kinematics were found between with and without the placement of the pressure sensor at all knee flexions (P > 0.05). Most of the ICC values for contact pressure, peak contact pressure, and contact area ranged from 0.8 to 0.9. The MDDs for rotational displacement were 0.9° and 0.6 mm for translational displacement. No statistical differences in patellar kinematics were found before and after the insertion of the pressure sensor.

Conclusions

The setup in the present study enables researchers to simultaneously and synchronously collect real‐time PFJ kinematics and tibiofemoral joint (TFJ) biomechanical kinematic data with high reliability. The low MDDs enabled the researchers to obtain an accurate interpretation of the kinematic and contact mechanics measurement using the experimental setting used in the present study.
Intermittent Parathyroid Hormone Alters Gut Microbiota in Ovariectomized Osteoporotic Rats
Authors: Zhou Jiaming , Wang Rui , Zhao Rui , Guo Xing , Gou Pengguo , Bai He , Lei Ping , Xue Yuan
Published: August 2022

Objective

To investigate the effect of intermittent parathyroid hormone (PTH) on gut microbiota (GM) in ovariectomized (OVX) osteoporotic rats.

Methods

Thirty female Sprague–Dawley rats were divided into three groups: sham‐operation (SHAM) group, OVX group and PTH treatment group. After 3 months of treatment, the femurs, serum and feces were acquired for micro‐CT, biochemical analysis and 16S rRNA sequencing, respectively. For 16S rRNA sequencing, after raw reads filtrated and chimera sequences removed, the clean reads were obtained. According to these clean reads, the operational taxonomic units (OTUs) were clustered. Venn diagram analysis was conducted to explore common and unique GM among the three groups. The α‐diversity analysis including Shannon and Simpson indexes were used to evaluate the richness and diversity of the GM. The β‐diversity analysis was performed to estimate the structure of GM. The metabolic function was predicted by Tax4Fun analysis.

Results

With micro‐CT and biochemical analysis, significant improvements were found in the PTH group compared with the OVX group. In Venn diagram analysis, more unique OTUs were found in the SHAM and PTH groups than the OVX group. According to the rank abundance curve, the SHAM and PTH groups had similar richness and evenness, which were higher than the OVX group. Simpson and Shannon indexes were higher in the SHAM and PTH groups compared with the OVX group, indicating that the SHAM and PTH groups had higher microbiota complexity than the OVX group. In β‐diversity analysis, apparent separation was found in the OVX group from the PTH and SHAM groups, which suggested that osteoporosis is the critical factor influencing the GM composition and PTH treatment and can restore the structure of GM. Compared with the OVX group, treatment with PTH increased the abundances of GM which were reported to increase bone mass, such asLactobacillus_reuteri,Muribaculaceae,Ruminococcaceae, andClostridia, and inhibited the relative abundance ofRikenellaceae, which was reported to be potentially related to osteoporosis. GM function analysis showed that PTH could promote butyrate synthesis. In Tax4Fun analysis, the function of butanoate metabolism is more vital in the PTH group than the OVX and SHAM groups, suggesting PTH treatment could regulate microbial metabolic function, including butanoate metabolism.

Conclusion

Intermittent PTH can interact with GM through increasing the abundance of probiotics and reducing the abundance of the pathogenic bacteria to enhance the bone mass.
Early‐onset hypertension associated with extensive cutaneous capillary malformations harboring postzygotic variants in GNAQ and GNA11
Authors: Davies Olivia M. T. , Ng Ashley T. , Tran Jennifer , Blumenthal Shoshana , Arkin Lisa M. , Nopper Amy J. , Cottrell Catherine E. , Garzon Maria , Siegel Dawn H. , Frieden Ilona J. , Drolet Beth A.
Published: August 2022

Background and Objectives

Cutaneous capillary malformations (CMs) describe a group of vascular birthmarks with heterogeneous presentations. CMs may present as an isolated finding or with other associations, including glaucoma and leptomeningeal angiomatosis (i.e., Sturge–Weber syndrome) or pigmentary birthmarks (i.e., phakomatosis pigmentovascularis). The use of targeted genetic sequencing has revealed that postzygotic somatic variations in GNAQ and GNA11 at codon 183 are associated with CMs. We report five patients with early‐onset hypertension and discuss possible pathogenesis of hypertension.

Methods

Twenty‐nine patients with CMs, confirmed GNAQ/11 postzygotic variants, and documented past medical history were identified from a multi‐institutional vascular anomalies study. Early‐onset hypertension was defined as hypertension before the age of 55 years. Clinical data were reviewed for evidence of hypertension, such as documentation of diagnosis or elevated blood pressure measurements.

Results

Five of the 29 patients identified as having GNAQ/11 postzygotic variants had documented early‐onset hypertension. Three individuals harbored a GNAQ p.R183Q variant, and two individuals harbored a GNA11 p.R183C variant. All individuals had extensive cutaneous CMs involving the trunk and covering 9%–56% of their body surface area. The median age of hypertension diagnosis was 15 years (range 11–24 years), with three individuals having renal abnormalities on imaging.

Conclusions

Early‐onset hypertension is associated with extensive CMs harboring somatic variations in GNAQ/11. Here, we expand on the GNAQ/11 phenotype and hypothesize potential mechanisms driving hypertension. We recommend serial blood pressure measurements in patients with extensive CMs on the trunk and extremities to screen for early‐onset hypertension.
Against ‘Against Slagle's Reading’
Authors: Slagle Jim
Published: August 2022

Serdal Tümkaya has argued that my critique of eliminative materialism makes several missteps. He argues that eliminativism should be taken as a methodology not a settled conclusion, and the final product may well retain some folk psychology concepts. I respond that methodological eliminativism does avoid self‐defeat but does not pose a problem for the folk psychologist. Plus, insofar as eliminativism is not eliminating the propositional attitudes but accomodating or translating them, it is not distinct from other, less extreme forms of materialism.
Holding points of view does not amount to knowledge
Authors: Miranda Vilchis Rogelio
Published: August 2022

I argue that knowing and having points of view are fundamentally different epistemic states if we assume that having justified true beliefs is necessary for knowledge. Knowers necessarily possess justified true beliefs, but persons holding points of view may, for example, lack justification, have false beliefs, or both. I examine these differences and expose other crucial differentiating patterns between the structure of knowledge and points of view that make the latter more likely to lead to disagreements. I hypothesize that these patterns remain invariant in alternative views of knowledge like contextualism as long as we preserve the classical structure. Yet there is much research to be done on the multiple and contrasting properties that emerge if we consider non‐classical analyses of knowledge and points of view.
Doing more among institutional boundaries: Platform‐enabled government in China
Authors: Zeng Yu , Zhang Quan , Zhao Qi , Huang Huang
Published: August 2022

The concept of Government as a Platform (GaaP) has recently encountered setbacks in practice worldwide. While existing literature on inter‐governmental collaboration has emphasized organizational restructuring and data sharing, this study argues that a pragmatic way to improve administrative efficiency in the absence of formal institutional change is to adopt an alternative model to GaaP: platform‐enabled government. Enabled by innovations of the middle‐tier platform, this new model of platform governance integrates the functions of distributed systems of multiple departments into a sequential workflow without the requirement of institutional reform or sharing proprietary data. To demonstrate how this model facilitates information flow across institutional boundaries and improves collaborative governance, we analyze horizontal, vertical, and public‐private collaboration using a diverse case study design. We examine administrative review, law enforcement, and contact tracing during the pandemic in the context of China. Our findings suggest accommodating institutional boundaries is a practical and effective approach to advance the digital government agenda in decentralized contexts.
Absent Presences in the Colonial Archive
Authors: Hilden Irene
Published: August 2022

The Berlin Sound Archive (Lautarchiv) consists of an extensive collection of sound recordings, compiled for scientific purposes in the first half of the 20th century. Recorded on shellac are stories and songs, personal testimonies and poems, glossaries and numbers. This book engages with the archive by consistently focusing on the colonial conditions under which the recordings were produced. With a firm commitment to postcolonial scholarship, Absent Presences in the Colonial Archive is a historical ethnography of a metropolitan institution that participated in the production and preservation by colonial structures of power and knowledge. The book examines sound objects and listening practices that render the coloniality of knowledge fragile and inconsistent, revealing the absent presences of colonial subjects who are given little or no place in established national narratives and collective memories.
Medición de la calidad del espacio público con la implementación de Transmilenio en Suba, Bogotá
Authors: Robles Cruz Charlixon Viscillinovick
Published: August 2022

En la teoría del desarrollo orientado al transporte (DOT), la calidad del espacio público (EP) y las características del tejido urbano deben responder a la implementación de los sistemas de transporte sostenible. Esta investigación acude a aportes teóricos del DOT para conformar diez indicadores de calidad del EP, valorando aspectos como: conectividad y accesibilidad, morfología, mixtura de usos, espacios de reunión, seguridad y confort. El caso de estudio es la zona de Suba en Bogotá, donde está construido el sistema Transmilenio desde 2006. En el análisis se utilizan bases de datos de acceso libre, sistemas de información geográfica (SIG) y técnicas de fotointerpretación multitemporal para determinar el cambio en los indicadores antes y después de la implementación de Transmilenio. Se encuentra que la calidad del EP es deficitaria y se evidencia que los principios del DOT no son suficientemente implementados en la zona de estudio
The combined effects of contextual predictability and noise on the acoustic realisation of German syllables
Authors: Ibrahim Omnia , Yuen Ivan , van Os Marjolein , Andreeva Bistra , Möbius Bernd
Published: August 2022

Speakers tend to speak clearly in noisy environments, while they tend to reserve effort by shortening word duration in predictable contexts. It is unclear how these two communicative demands are met. The current study investigates the acoustic realizations of syllables in predictable vs unpredictable contexts across different background noise levels. Thirty-eight German native speakers produced 60 CV syllables in two predictability contexts in three noise conditions (reference = quiet, 0 dB and −10 dB signal-to-noise ratio). Duration, intensity (average and range), F0 (median), and vowel formants of the target syllables were analysed. The presence of noise yielded significantly longer duration, higher average intensity, larger intensity range, and higher F0. Noise levels affected intensity (average and range) and F0. Low predictability syllables exhibited longer duration and larger intensity range. However, no interaction was found between noise and predictability. This suggests that noise-related modifications might be independent of predictability-related changes, with implications for including channel-based and message-based formulations in speech production.
Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection
Authors: Wang Jing , Zhou Cai , Gao Shuai , Song Xiuling , Yang Xinyan , Fan Jiaqi , Ren Shaofang , Ma Linzi , Zhao Jiexiang , Cui Manman , Song Ke , Wang Mei , Li Chaohui , Zheng Yi , Luo Fang , Miao Kai , Bai Xiaochun , Hutchins Andrew P. , Li Lin , Chang Gang , Zhao Xiao-Yang
Published: August 2022

Round spermatid injection (ROSI) technique holds great promise for clinical treatment of a proportion of infertile men. However, the compromised developmental potential of ROSI embryos largely limits the clinical application, and the mechanisms are not fully understood. Here, we describe the transcriptome, chromatin accessibility, and DNA methylation landscapes of mouse ROSI embryos derived from early-stage round spermatids using a single-cell multiomics sequencing approach. By interrogating these data, we identify the reprogramming defects in ROSI embryos at the pronuclear stages, which are mainly associated with the misexpression of a cohort of minor zygotic genome activation genes. We screen a small compound, A366, that can significantly increase the developmental potential of ROSI embryos, in which A366 can partially overcome the reprogramming defects by amending the epigenetic and transcriptomic states. Collectively, our study uncovers the reprogramming defects in ROSI embryos for understanding the mechanisms underlying compromised developmental potential and offers an avenue for ROSI technique optimization.
Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy
Authors: Zhang Xiao-Wen , Feng Na , Liu Yan-Chen , Guo Qiang , Wang Jing-Kang , Bai Yi-Zhen , Ye Xiao-Ming , Yang Zhuo , Yang Heng , Liu Yang , Yang Mi-Mi , Wang Yan-Hang , Shi Xiao-Meng , Liu Dan , Tu Peng-Fei , Zeng Ke-Wu
Published: August 2022

Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys
576
, in a unique noncatalytic HUBL domain. By selectively modifying Cys
576
, EB allosterically inhibits USP7 to cause a ubiquitination-dependent degradation of Keap1. Keap1 function loss further results in an Nrf2-dependent transcription activation of anti-neuroinflammation genes in microglia. In vivo, pharmacological USP7 inhibition attenuates microglia activation and resultant neuron injury, thereby notably improving behavioral deficits in dementia and Parkinson’s disease mouse models. Collectively, our findings provide an attractive future direction for neurodegenerative disease therapy by inhibiting microglia-mediated neuroinflammation by targeting USP7.
Network topology–directed design of molecular CPU for cell-like dynamic information processing
Authors: Wang Dan , Yang Yani , Chen Fengming , Lyu Yifan , Tan Weihong
Published: August 2022

Natural cells (NCs) can automatically and continuously respond to fluctuant external information and distinguish meaningful stimuli from weak noise depending on their powerful genetic and protein networks. We herein report a network topology–directed design of dynamic molecular processing system (DMPS) as a molecular central processing unit that powers an artificial cell (AC) able to process fluctuant information in its immediate environment similar to NCs. By constructing a mixed cell community, ACs and NCs have synchronous response to fluctuant extracellular stimuli under physiological condition and in a blood vessel–mimic circulation system. We also show that fluctuant bioinformation released by NCs can be received and processed by ACs. The molecular design of DMPS-powered AC is expected to allow a profound understanding of biological systems, advance the construction of intelligent molecular systems, and promote more elegant bioengineering applications.
Facet-selective etching trajectories of individual semiconductor nanocrystals
Authors: Yan Chang , Byrne Dana , Ondry Justin C. , Kahnt Axel , Moreno-Hernandez Ivan A. , Kamat Gaurav A. , Liu Zi-Jie , Laube Christian , Crook Michelle F. , Zhang Ye , Ercius Peter , Alivisatos A. Paul
Published: August 2022

The size and shape of semiconductor nanocrystals govern their optical and electronic properties. Liquid cell transmission electron microscopy (LCTEM) is an emerging tool that can directly visualize nanoscale chemical transformations and therefore inform the precise synthesis of nanostructures with desired functions. However, it remains difficult to controllably investigate the reactions of semiconductor nanocrystals with LCTEM, because of the highly reactive environment formed by radiolysis of liquid. Here, we harness the radiolysis processes and report the single-particle etching trajectories of prototypical semiconductor nanomaterials with well-defined crystalline facets. Lead selenide nanocubes represent an isotropic structure that retains the cubic shape during etching via a layer-by-layer mechanism. The anisotropic arrow-shaped cadmium selenide nanorods have polar facets terminated by either cadmium or selenium atoms, and the transformation trajectory is driven by etching the selenium-terminated facets. LCTEM trajectories reveal how nanoscale shape transformations of semiconductors are governed by the reactivity of specific facets in liquid environments.
Spin-induced asymmetry reaction—The formation of asymmetric carbon by electropolymerization
Authors: Bhowmick Deb Kumar , Das Tapan Kumar , Santra Kakali , Mondal Amit Kumar , Tassinari Francesco , Schwarz Rony , Diesendruck Charles E. , Naaman Ron
Published: August 2022

We describe the spin polarization–induced chirogenic electropolymerization of achiral 2-vinylpyridine, which forms a layer of enantioenhanced isotactic polymer on the electrode. The product formed is enantioenriched in asymmetric carbon polymer. To confirm the chirality of the polymer film formed on the electrode, we also measured its electron spin polarization properties as a function of its thickness. Two methods were used: First, spin polarization was measured by applying magnetic contact atomic force microscopy, and second, magnetoresistance was assessed in a sandwich-like four-point contact structure. We observed high spin-selective electron transmission, even for a layer thickness of 120 nm. A correlation exists between the change in the circular dichroism signal and the change in the spin polarization, as a function of thickness. The spin-filtering efficiency increases with temperature.
Fluidic innervation sensorizes structures from a single build material
Authors: Truby Ryan L. , Chin Lillian , Zhang Annan , Rus Daniela
Published: August 2022

Multifunctional materials with distributed sensing and programmed mechanical properties are required for myriad emerging technologies. However, current fabrication techniques constrain these materials’ design and sensing capabilities. We address these needs with a method for sensorizing architected materials through fluidic innervation, where distributed networks of empty, air-filled channels are directly embedded within an architected material’s sparse geometry. By measuring pressure changes within these channels, we receive feedback regarding material deformation. Thus, this technique allows for three-dimensional printing of sensorized structures from a single material. With this strategy, we fabricate sensorized soft robotic actuators on the basis of handed shearing auxetics and accurately predict their kinematics from the sensors’ proprioceptive feedback using supervised learning. Our strategy for facilitating structural, sensing, and actuation capabilities through control of form alone simplifies sensorized material design for applications spanning wearables, smart structures, and robotics.
Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice
Authors: Melica Maria Elena , Antonelli Giulia , Semeraro Roberto , Angelotti Maria Lucia , Lugli Gianmarco , Landini Samuela , Ravaglia Fiammetta , Regina Gilda La , Conte Carolina , De Chiara Letizia , Peired Anna Julie , Mazzinghi Benedetta , Donati Marta , Molli Alice , Steiger Stefanie , Magi Alberto , Bartalucci Niccolò , Raglianti Valentina , Guzzi Francesco , Maggi Laura , Annunziato Francesco , Burger Alexa , Lazzeri Elena , Anders Hans-Joachim , Lasagni Laura , Romagnani Paola
Published: August 2022

Crescentic glomerulonephritis is characterized by vascular necrosis and parietal epithelial cell hyperplasia in the space surrounding the glomerulus, resulting in the formation of crescents. Little is known about the molecular mechanisms driving this process. Inducing crescentic glomerulonephritis in two Pax2Cre reporter mouse models revealed that crescents derive from clonal expansion of single immature parietal epithelial cells. Preemptive and delayed histone deacetylase inhibition with panobinostat, a drug used to treat hematopoietic stem cell disorders, attenuated crescentic glomerulonephritis with recovery of kidney function in the two mouse models. Three-dimensional confocal microscopy and stimulated emission depletion superresolution imaging of mouse glomeruli showed that, in addition to exerting an anti-inflammatory and immunosuppressive effect, panobinostat induced differentiation of an immature hyperplastic parietal epithelial cell subset into podocytes, thereby restoring the glomerular filtration barrier. Single-cell RNA sequencing of human renal progenitor cells in vitro identified an immature stratifin-positive cell subset and revealed that expansion of this stratifin-expressing progenitor cell subset was associated with a poor outcome in human crescentic glomerulonephritis. Treatment of human parietal epithelial cells in vitro with panobinostat attenuated stratifin expression in renal progenitor cells, reduced their proliferation, and promoted their differentiation into podocytes. These results offer mechanistic insights into the formation of glomerular crescents and demonstrate that selective targeting of renal progenitor cells can attenuate crescent formation and the deterioration of kidney function in crescentic glomerulonephritis in mice.
The past, present, and future of antibiotics
Authors: Cook Michael A. , Wright Gerard D.
Published: August 2022

Antibiotics have transformed modern medicine. They are essential for treating infectious diseases and enable vital therapies and procedures. However, despite this success, their continued use in the 21st century is imperiled by two orthogonal challenges. The first is that the microbes targeted by these drugs evolve resistance to them over time. The second is that antibiotic discovery and development are no longer cost-effective using traditional reimbursement models. Consequently, there are a dwindling number of companies and laboratories dedicated to delivering new antibiotics, resulting in an anemic pipeline that threatens our control of infections. The future of antibiotics requires innovation in a field that has relied on highly traditional methods of discovery and development. This will require substantial changes in policy, quantitative understanding of the societal value of these drugs, and investment in alternatives to traditional antibiotics. These include narrow-spectrum drugs, bacteriophage, monoclonal antibodies, and vaccines, coupled with highly effective diagnostics. Addressing the antibiotic crisis to meet our future needs requires considerable investment in both research and development, along with ensuring a viable marketplace that encourages innovation. This review explores the past, present, and future of antimicrobial therapy.
Effectiveness of HEPA Filters at Removing Infectious SARS-CoV-2 from the Air
Authors: Ueki Hiroshi , Ujie Michiko , Komori Yosuke , Kato Tatsuo , Imai Masaki , Kawaoka Yoshihiro
Published: August 2022

Air filtration simulation experiments quantitatively showed that an air cleaner equipped with a HEPA filter can continuously remove SARS-CoV-2 from the air. The capture ratios for SARS-CoV-2 in the air when the air cleaner was equipped with an antiviral-agent-coated HEPA filter were comparable to those with the conventional HEPA filter, and there was little effect on SARS-CoV-2 in the air that passed through the antiviral-reagent-coated HEPA filter.
Changes in Composition and Diversity of Epiphytic Microorganisms on Field Pea Seeds, Partial Crop Peas, and Whole Crop Peas during Maturation and Ensiling with or without Lactic Acid Bacteria Inoculant
Authors: Bachmann Martin , Wensch-Dorendorf Monika , Kuhnitzsch Christian , Kleinsteuber Sabine , Popp Denny , Thierbach Annabel , Martens Siriwan D. , Steinhöfel Olaf , Zeyner Annette
Published: August 2022

Field peas are important protein suppliers for human and animal nutrition. They can be grown in many areas of the world, which may reduce imports of protein plants and has beneficial economic and ecological effects.
Machine learning forecasting for COVID-19 pandemic-associated effects on paediatric respiratory infections
Authors: Bowyer Stuart A , Bryant William A , Key Daniel , Booth John , Briggs Lydia , Spiridou Anastassia , Cortina-Borja Mario , Davies Gwyneth , Taylor Andrew M , Sebire Neil J
Published: August 2022

Objective

The COVID-19 pandemic and subsequent government restrictions have had a major impact on healthcare services and disease transmission, particularly those associated with acute respiratory infection. This study examined non-identifiable routine electronic patient record data from a specialist children’s hospital in England, UK, examining the effect of pandemic mitigation measures on seasonal respiratory infection rates compared with forecasts based on open-source, transferable machine learning models.

Methods

We performed a retrospective longitudinal study of respiratory disorder diagnoses between January 2010 and February 2022. All diagnoses were extracted from routine healthcare activity data and diagnosis rates were calculated for several diagnosis groups. To study changes in diagnoses, seasonal forecast models were fit to prerestriction period data and extrapolated.

Results

Based on 144 704 diagnoses from 31 002 patients, all but two diagnosis groups saw a marked reduction in diagnosis rates during restrictions. We observed 91%, 89%, 72% and 63% reductions in peak diagnoses of ‘respiratory syncytial virus’, ‘influenza’, ‘acute nasopharyngitis’ and ‘acute bronchiolitis’, respectively. The machine learning predictive model calculated that total diagnoses were reduced by up to 73% (z-score: −26) versus expected during restrictions and increased by up to 27% (z-score: 8) postrestrictions.

Conclusions

We demonstrate the association between COVID-19 related restrictions and significant reductions in paediatric seasonal respiratory infections. Moreover, while many infection rates have returned to expected levels postrestrictions, others remain supressed or followed atypical winter trends. This study further demonstrates the applicability and efficacy of routine electronic record data and cross-domain time-series forecasting to model, monitor, analyse and address clinically important issues.
Knowledge user survey and Delphi process to inform development of a new risk of bias tool to assess systematic reviews with network meta-analysis (RoB NMA tool)
Authors: Lunny Carole , Veroniki Areti Angeliki , Hutton Brian , White Ian , Higgins JPT , Wright James M , Kim Ji Yoon , Thirugnanasampanthar Sai Surabi , Siddiqui Shazia , Watt Jennifer , Moja Lorenzo , Taske Nichole , Lorenz Robert C , Gerrish Savannah , Straus Sharon , Minogue Virginia , Hu Franklin , Lin Kevin , Kapani Ayah , Nagi Samin , Chen Lillian , Akbar-nejad Mona , Tricco Andrea C
Published: August 2022

Background

Network meta-analysis (NMA) is increasingly used in guideline development and other aspects of evidence-based decision-making. We aimed to develop a risk of bias (RoB) tool to assess NMAs (RoB NMA tool). An international steering committee recommended that the RoB NMA tool to be used in combination with the Risk of Bias in Systematic reviews (ROBIS) tool (i.e. because it was designed to assess biases only) or other similar quality appraisal tools (eg, A MeaSurement Tool to Assess systematic Reviews 2 [AMSTAR 2]) to assess quality of systematic reviews. The RoB NMA tool will assess NMA biases and limitations regarding how the analysis was planned, data were analysed and results were presented, including the way in which the evidence was assembled and interpreted.

Objectives

Conduct (a) a Delphi process to determine expert opinion on an item’s inclusion and (b) a knowledge user survey to widen its impact.

Design

Cross-sectional survey and Delphi process.

Methods

Delphi panellists were asked to rate whether items should be included. All agreed-upon item were included in a second round of the survey (defined as 70% agreement). We surveyed knowledge users’ views and preferences about the importance, utility and willingness to use the RoB NMA tool to evaluate evidence in practice and in policymaking. We included 12 closed and 10 open-ended questions, and we followed a knowledge translation plan to disseminate the survey through social media and professional networks.

Results

22 items were entered into a Delphi survey of which 28 respondents completed round 1, and 22 completed round 2. Seven items did not reach consensus in round 2. A total of 298 knowledge users participated in the survey (14% respondent rate). 75% indicated that their organisation produced NMAs, and 78% showed high interest in the tool, especially if they had received adequate training (84%). Most knowledge users and Delphi panellists preferred a tool to assessbothbias in individual NMA resultsandauthors’ conclusions. Response bias in our sample is a major limitation as knowledge users working in high-income countries were more represented. One of the limitations of the Delphi process is that it depends on the purposive selection of experts and their availability, thus limiting the variability in perspectives and scientific disciplines.

Conclusions

This Delphi process and knowledge user survey informs the development of the RoB NMA tool.