bluuebunny/crossref_metadata_2025 huggingface dataset:
High Rates of Quinone‐Alkyne Cycloaddition Reactions are Dictated by Entropic Factors
Authors: Damen Johannes A. M. , Escorihuela Jorge , Zuilhof Han , van Delft Floris L. , Albada Bauke
Published: March 2023

Reaction rates of strained cycloalkynes and cycloalkenes with 1,2‐quinone were quantified by stopped flow UV‐Vis spectroscopy and computational analysis. We found that the strained alkyne BCN−OH 3 (k2 1824 M−1 s−1) reacts >150 times faster than the strained alkene TCO‐OH 5 (k2 11.56 M−1 s−1), and that derivatization with a carbamate can lead to a reduction of the rate constant with almost half. Also, the 8‐membered strained alkyne BCN−OH 3 reacts 16 times faster than the more strained 7‐membered THS 2 (k2 110.6 M−1 s−1). Using the linearized Eyring equation we determined the thermodynamic activation parameters of these two strained alkynes, revealing that the SPOCQ reaction of quinone 1 with THS 2 is associated with ΔH≠ of 0.80 kcal/mol, ΔS≠=−46.8 cal/K⋅mol, and ΔG≠=14.8 kcal/mol (at 25 °C), whereas the same reaction with BCN−OH 3 is associated with, ΔH≠=2.25 kcal/mol, ΔS≠=−36.3 cal/K⋅mol, and ΔG≠=13.1 kcal/mol (at 25 °C). Computational analysis supported the values obtained by the stopped‐flow measurements, with calculated ΔG≠ of 15.6 kcal/mol (in H2O) for the SPOCQ reaction with THS 2, and with ΔG≠ of 14.7 kcal/mol (in H2O) for the SPOCQ reaction with BCN−OH 3. With these empirically determined thermodynamic parameters, we set an important step towards a more fundamental understanding of this set of rapid click reactions.
Tetraphenylethene‐Based cis/trans Isomers for Targeted Fluorescence Sensing and Biomedical Applications
Authors: Huang Yanyan , Zhang Guanxin , Zhao Rui , Zhang Deqing
Published: March 2023

Molecular probes which can be modulated, functionalized and used to visualize the processes are highly desirable for understanding and manipulating biological systems. Geometric cis and trans isomers of tetraphenylethene (TPE) emerge as attractive candidates to fulfill these tasks thanks to the unique aggregation‐induced emission properties, tailorable structures, and responsiveness to external stimuli. This minireview focuses on cis and trans isomers of TPE derivatives that are functionalized with molecular recognition units for fluorescence detection, bioimaging and cancer therapy. The effects of molecular geometry on fluorescence property, target binding ability and biological activity are summarized. The feasibility to in vitro and in vivo switch molecular configuration and thus bio‐activity is discussed. Finally, the future development and challenges are discussed in view of TPE‐based stereoisomers for targeted sensing and imaging‐guided modulation of biological processes.
Analysis of the fecal metagenome in long‐term survivors of pancreas cancer
Authors: Kharofa Jordan , Haslam David , Wilkinson Rachael , Weiss Allison , Patel Sameer , Wang Kyle , Esslinger Hope , Olowokure Olugbenga , Sohal Davendra , Wilson Greg , Ahmad Syed , Apewokin Senu
Published: March 2023

Background

The 5‐year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long‐term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long‐term survival are not well described.

Methods

In this cross‐sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long‐term survival (n = 16). LTS was defined as >4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls.

Results

All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4–14 years) for LTSs without evidence of disease compared to a median disease‐free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia muciniphila species.

Conclusions

Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia muciniphila. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.

Plain Language Summary

Although pancreatic cancer treatments have improved, the number of long‐term survivors has remained stagnant with a 5‐year overall survival estimate of 9%.

Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system.

In this study, we profiled the stool microbiome in long‐term survivors of pancreas cancer and controls.

Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia muciniphila.

These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.
Phosphorous/Fluorine Co‐doped Biomass‐derived Carbon for Enhanced Sodium‐ion and Lithium‐ion Storage
Authors: Dutta Dimple P. , Modak Brindaban , Ravuri Balaji Rao
Published: March 2023

Carbon from inexpensive biomass‐based precursors have shown promise as anode materials for application in sodium/lithium ion battery technology. However, their practical implementation is marred by unreliable cycling stability and unimpressive initial coulombic efficiency. The electrochemical properties of such biomass derived carbon can be improved considerably by material engineering via suitable heteroatom doping. In this work, the effect of phosphorous and fluorine doping on naseberry seed derived carbon has been explored. The doping led to an increase in the specific capacity and rate performance of the modified bio‐based carbon in comparison to non‐doped counterparts. The P/F incorporated carbon delivers reversible capacity of 812 mAh g−1 and 409 mAh g−1 at 0.1 A g−1 when tested as anode in lithium/sodium ion coin cell. The long term cycling of the material at a higher current rate of 1.0 A g−1 is also impressive. The reason for this enhanced electrochemical performance has been analysed through electrochemical impedance spectroscopy and post mortem electron microscopic studies. The increase in interlayer spacing, cell volume and ionic conductivity in the P/F incorporated carbon which leads to an improvement in the electrochemical properties has also been corroborated via DFT analysis.
Single‐ and Multiple‐dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP1128, a Novel Peroxisome Proliferator‐activated Receptor δ Modulator, in Healthy Participants
Authors: Taniuchi Yuta , van Till J. W. Olivier , Wojtkowski Tomasz , Toyoshima Junko , Koibuchi Akira , Sargent Briana , Han David
Published: March 2023

Peroxisome proliferator‐activated receptor δ (PPARδ) plays a central role in modulating mitochondrial function in ischemia‐reperfusion injury. ASP1128, a potent and selective modulator of PPARδ, is currently under investigation for treating acute kidney injury. This randomized, first‐in‐human study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of ASP1128 administered intravenously in healthy participants. Forty‐nine participants received a single dose of ASP1128 0.3–10 mg (n = 37) or placebo (n = 12) and 53 received daily (7 days) doses of ASP1128 3–100 mg (n = 39) or placebo (n = 14), including a cohort aged ≥65 years (ASP1128 100 mg, n = 3; placebo, n = 2). Treatment‐emergent adverse events occurred in 37.8%, 59.0%, and 33.3%–35.7% of participants in the single ASP1128, multiple ASP1128, and placebo groups, respectively. All were mild in severity, and the frequency of adverse events did not appear to be dose‐related. One participant (multiple ASP1128 3 mg group) withdrew with an infusion site erythema, possibly related to study drug. Exposure was roughly dose‐proportional, and elimination was generally consistent across doses (mean t½ 14.6–17.4 hours in the 10, 30, and 100 mg groups on day 7). There was little accumulation in plasma following multiple dosing; steady state was reached after ∼4 days. ASP1128 treatment led to rapid and dose‐related upregulation of six fatty acid oxidation‐related PPARδ target genes at ≥10 mg, which lasted >24 hours postdose. In conclusion, single and multiple intravenous doses of ASP1128 were generally well tolerated, with dose‐dependent pharmacokinetics and target gene engagement in healthy participants.
The Chemistry of P=N−P=X (X=S, O, NR) Linkages for the Synthesis of Dendritic Structures
Authors: Maraval Valérie , Laurent Régis , Caminade Anne‐Marie
Published: March 2023

The Staudinger reaction between a phosphine and an azide, applied to phosphorus azides, has been used for the synthesis of a large variety of dendritic structures, incorporating P=N−P=X moieties (X = mainly S, but also O and N−R). Conjugation of the P=N bond with the P=X bond greatly stabilizes the P=N bond. Highly branched structures such as dendrons, dendrimers, Janus dendrimers, layered dendrimers, surface‐block dendrimers, and diverse other dendritic structures incorporating such linkage have been elaborated. Accelerated methods of synthesis of dendrimers are also based on the Staudinger reaction. A versatile reactivity was observed exclusively on the sulfur atom of P=N−P=S linkages, such as alkylation or complexation. Alkylation on S induces a weakening of the strength of the P=S bond, which can be easily cleaved to generate phosphines able to react in Staudinger reactions inside the structure of dendrimers, thus affording highly sophisticated dendritic structures.
UniProt Tools: BLAST, Align, Peptide Search, and ID Mapping
Authors: Zaru Rossana , Orchard Sandra ,   The UniProt Consortium
Published: March 2023

The Universal Protein Resource (UniProt) is a comprehensive resource for protein sequence and annotation data (UniProt Consortium, 2023). The UniProt website receives about 800,000 unique visitors per month and is the primary means to access UniProt. Along with various datasets that you can search, UniProt provides four main tools. These are the “BLAST” tool for sequence similarity searching, the “Align” tool for multiple sequence alignment, the “Peptide Search” tool for retrieving proteins containing a short peptide sequence, and the “Retrieve/ID Mapping” tool for using a list of identifiers to retrieve UniProt Knowledgebase (UniProtKB) proteins and to convert database identifiers from UniProt to external databases or vice versa. This article provides four basic protocols and seven alternate protocols for using UniProt tools. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Basic local alignment search tool (BLAST) in UniProt

Alternate Protocol 1: BLAST through UniProt text search results pages

Alternate Protocol 2: BLAST through UniProt basket

Basic Protocol 2: Multiple sequence alignment in UniProt

Alternate Protocol 3: Align tool through UniProt results pages and entry pages

Alternate Protocol 4: Align tool through UniProt basket

Basic Protocol 3: Peptide search in UniProt

Basic Protocol 4: Batch retrieval and ID mapping in UniProt

Alternate Protocol 5: Retrieve/ID Mapping tool through UniProt text search results pages and BLAST and Align results pages

Alternate Protocol 6: Retrieve/ID Mapping tool through UniProt basket

Alternate Protocol 7: Retrieve/ID Mapping tool through UniProt search box
RNS processor using moduli sets of the form 2n±1
Authors: Prediger Vanessa , Bairros Fábio , Seman Laio Oriel , Bezerra Eduardo Augusto , Pettenghi Héctor
Published: March 2023

In recent years, research on residue number systems (RNS) has targeted larger dynamic ranges to explore their inherent parallelism further. In this paper, we start from the traditional 3‐moduli set , with an equivalent 3 ‐bit dynamic range, and propose balanced horizontal extensions by using modulus of the form and to scale the dynamic range and enhance the parallelism according to the requirements. A method to design the reverse conversion by using it is also presented. A case study of multiplier‐accumulator (MACs) in cascade for filtering applications has been analyzed to validate the RNS processor using the proposed moduli set and reverse conversion architecture. Experimental results show that the proposed approaches achieve a significant speedup compared with the state‐of‐the‐art cases for the same dynamic range purposes.
Adoptive T‐cell therapy targeting Epstein–Barr virus as a treatment for multiple sclerosis
Authors: Smith Corey , Khanna Rajiv
Published: March 2023

Emergence of a definitive link between Epstein–Barr virus (EBV) and multiple sclerosis has provided an impetus to develop immune‐based therapies to target EBV‐infected B cells. Initial studies with autologous EBV‐specific T‐cell therapy demonstrated that this therapy is safe with minimal side effects and more importantly multiple patients showed both symptomatic and objective neurological improvements including improved quality of life, reduction of fatigue and reduced intrathecal IgG production. These observations have been successfully extended to an ‘off‐the‐shelf’ allogeneic EBV‐specific T‐cell therapy manufactured using peripheral blood lymphocytes of healthy seropositive individuals. This adoptive immunotherapy has also been shown to be safe with encouraging clinical responses. Allogeneic EBV T‐cell therapy overcomes some of the limitations of autologous therapy and can be rapidly delivered to patients with improved therapeutic potential.
Temperature‐Derived Fe Dissolution of a LiFePO4/Graphite Cell at Fast Charging and High State‐of‐Charge Condition
Authors: Rikka Vallabha Rao , Sahu Sumit Ranjan , Gurumurthy Mrinalini , Chatterjee Abhijit , Chandran Sudakar , Sundararajan Govindan , Gopalan Raghavan , Prakash Raju
Published: March 2023

Recently, the cathode materials employed in lithium‐ion batteries are dominated by transition metal oxides, phosphates, and spinels which are known to undergo a rapid capacity fade due to the synergistic effect of transition metal dissolution and lithium plating, especially at higher operating voltages and at elevated temperatures. However, solutions to mitigate these issues are unavailable largely due to the incomplete understanding of the complexity of the capacity fade mechanism at high state‐of‐charge and fast charging rates. Herein, a comprehensive experimental evidence linking to the high cell temperature as the main origin of Fe dissolution in the LiFePO4/graphite cell is provided. After 400 complete charge–discharge cycles at 4C, Fe dissolution is accelerated and is shortly followed by the deposition of Fe on graphite anode, and the subsequent formation of Fe‐catalyzed solid electrolyte interface layer at the anode. The dissolution–deposition process accounts for nearly 17–20% of the capacity loss against the initial capacity as observed in our experiments.
Introducing the No-Significant-Effect Concentration
Authors: Fisher Rebecca , Fox David R.
Published: March 2023

The no-effect concentration (NEC) is the preferred threshold metric for single-species toxicity tests applied to derive safe concentration thresholds for contaminants in the environment for use in species sensitivity distributions. However, the NEC is only suitable when concentration–response (C-R) data exhibit a threshold response. We describe an alternative toxicity estimate, the no-significant-effect concentration (NSEC), which is better suited to C-R data for which the response is a monotonically decreasing function of concentration and no threshold effects are evident. We use a flexible, three-parameter sigmoidal function to describe the C-R relationship and detail both Bayesian and frequentist approaches to estimation and inference for the NSEC. While the NSEC is conceptually linked to the traditional no-observed-effect concentration (NOEC), it is a substantial improvement over the NOEC because it decouples the estimate from being directly dependent on the placement of treatment concentrations as well as admitting statements of precision of the resulting toxicity estimate. Environ Toxicol Chem 2023;42:2019–2028. © 2023 Commonwealth of Australia and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Using Plasma Vitellogenin in Loggerhead Sea Turtles to Assess Reproductive Maturation and Estrogen-Like Contaminant Exposure
Authors: Corniuk Raquel N. , Lynch Jennifer M. , Arendt Michael D. , Braun-McNeill Joanne , Owens David W. , Valverde Roldán A. , Kucklick John R. , McClellan-Green Patricia D.
Published: March 2023

Vitellogenin (VTG), an egg yolk precursor, is abnormally produced by male and juvenile oviparous species after exposure to estrogens. Plasma VTG in loggerhead sea turtles (Caretta caretta) helped us understand their reproductive maturation and investigate it as a biomarker of contaminant exposure. The presence of VTG was screened in plasma from 404 loggerheads from the northwestern Atlantic Ocean using a freshwater turtle antibody in western blots. The concentrations of VTG were semiquantified using band intensities calibrated to results from a loggerhead antibody enzyme-linked immunoassay. The detection and concentrations of VTG were in (from highest to lowest): nesting females, in-water adult females, subadult females, smaller females, unknown sex, and males. Loggerheads from this region begin vitellogenesis at ≅77 cm straight carapace length. We classified VTG expression as abnormal in nine male or juvenile turtles. Organochlorine contaminant (OC) concentrations were measured in blood and/or fat biopsies of some turtles. One abnormal VTG female had the second highest fat polychlorinated biphenyl (PCB) and 4,4′-dichlorodiphenyldichloroethylene concentrations compared among 43 VTG-negative juveniles. The nine VTG-abnormal turtles had average blood PCB concentrations 8.5% higher, but not significantly different, than 46 VTG-negative juveniles (p = 0.453). In turtles less than 77 cm, blood PCB concentrations were significantly, but weakly, correlated with semiquantified VTG concentrations (tau = 0.1, p = 0.004). Greater blood OC concentrations were found in adult females than in males, which motivated the creation of a conceptual model of OC, VTG, and hormone concentrations across a reproductive cycle. A decision tree is also provided incorporating VTG as a sexing tool. Abnormal VTG expression cannot conclusively be linked to endocrine disruption caused by these OC concentrations. Studies should further investigate causes of abnormal VTG expression in wild sea turtles. Environ Toxicol Chem 2023;42:1309–1325. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Developing health information systems in developing countries: Lessons learnt from a longitudinal action research study in Vietnam
Authors: Nguyen Thanh Ngoc
Published: March 2023

Designing and implementing health information systems (HISs) in developing‐country settings is challenging. Many HISs do not go beyond the pilot stage and tend to vanish when external funding is over. In other cases, multiple fragmented HISs remain, but these are unable to talk to each other. And more often than not, data collected by HISs are not used in decision making. To better understand and address these problems, this article employs an information infrastructure (II) perspective and views HISs as parts of larger and complex social‐technical networks. This article contributes to the current knowledge with a set of rich empirical descriptions of the design and implementation of HISs in Vietnam. Theoretically, it contributes to II discussions in the information systems domain by presenting four design problems and suggesting five design principles and 15 design rules to meet them. These design principles and rules also offer practical guidance for managers and designers involved in the design and implementation of HISs in developing countries.
Simple bio‐inspired coating of ureteral stent for protein and bacterial fouling and calcium encrustation control
Authors: Gonzales Ralph Rolly , Kumagai Kazuo , Yang Zhe , Yang Youngmin , Shigemura Katsumi , Matsuyama Hideto
Published: March 2023

Encrustation, caused by deposition of calcium and magnesium salts present in urine, is a common problem of indwelling urinary devices, such as ureteral stent. Encrustation was also found to be related to urinary tract infections; thus, it is necessary to prepare ureteral stents with antibacterial and antifouling surfaces to mitigate the occurrence of encrustation. In this study, commercial ureteral stent was coated with polydopamine (PDA), formed from self‐polymerization of dopamine. The PDA coating was optimized in terms of dopamine concentration, pH, and coating time using response surface methodology. The chosen response parameters for optimization were calcium oxalate (CaC2O4) encrustation and protein adsorption. Optimized PDA coating conditions were determined to be the following: pH 9.0, 2 mg/mL DA, and 3 days coating. The optimized PDA‐coated ureteral stent exhibited outstanding resistance against CaC2O4 encrustation, protein fouling, and bacterial adhesion due to its hydrophilic and functional coating layer. In comparison with the pristine ureteral stent, PDA coating was able to suppress approximately 97% and 87% of CaC2O4 and protein adsorption, respectively. The PDA‐coated ureteral stent was compared against those of commercially available ureteral stents and found to have superior encrustation and protein fouling mitigation performance. Finally, PDA coating was found to be highly stable for a storage period of 90 days, whether stored in wet or dry conditions.
Potent SARS‐CoV2‐specific T‐cell response in asymptomatic hemodialysis patients with hidden COVID‐19 infection history
Authors: Etemadi Jalal , Motavalli Roza , Mirghaffari Seyed Alireza , Soltani‐Zangbar Mohammad Sadegh , Hajivalili Mahsa , Ahmadian Heris Javad , Niknafs Bahram , Zununi Sepideh , Sadeghi Mohammadreza , Rasi Hashemi Sadraddin , Tayebi Khosroshahi Hamid , Yousefi Mehdi
Published: March 2023

Background

COVID‐19‐related immune responses in patients with end‐stage renal disease (ESRD) are characterized in detail by the humoral response, but their cellular immunity has not been clarified. Here, we evaluated virus‐specific T cells in parallel with serology‐related tests.

Methods

In this study, 104 ESRD patients at the hemodialysis ward of Imam Reza hospital at Tabriz (Iran) were enrolled. After blood sampling, SARS‐CoV2‐specific humoral and cellular immune responses were evaluated by SARS‐CoV2‐specific IgM/IgG ELISA and peptide/MHCI‐Tetramers flow cytometry, respectively.

Results

Our results showed that 14 (13.5%) and 45 (43.3%) patients had specific SARS‐CoV2 IgM and IgG in their sera, respectively. Immunophenotyping for SARS‐CoV2‐specific CD8+ T lymphocytes revealed that 68 (65.4%) patients had these types of cells. Among SARS‐CoV2‐specific CD8+ T lymphocytes positive subjects, 13 and 43 individuals had positive results for specific SARS‐CoV2 IgM and IgG existence, respectively. Also, there was a relationship between specific SARS‐CoV2 IgM (p = 0.031) and IgG (p < 0.0001) existence and having SARS‐CoV2‐specific TCD8+ lymphocytes in the studied population.

Conclusion

Despite not having clinical symptoms, a high rate of SARS‐CoV2‐specific T‐cell response in asymptomatic ESRD patients may reveal a high burden of asymptomatic COVID‐19 infection in these patients.
Mobility and HIV care engagement: a research agenda
Authors: Thorp Marguerite , Ayieko James , Hoffman Risa M. , Balakasi Kelvin , Camlin Carol S. , Dovel Kathryn
Published: March 2023

Introduction

Mobility is common and an essential livelihood strategy in sub‐Saharan Africa (SSA). Mobile people suffer worse outcomes at every stage of the HIV care cascade compared to non‐mobile populations. Definitions of mobility vary widely, and research on the role of temporary mobility (as opposed to permanent migration) in HIV treatment outcomes is often lacking. In this article, we review the current landscape of mobility and HIV care research to identify what is already known, gaps in the literature, and recommendations for future research.

Discussion

Mobility in SSA is closely linked to income generation, though caregiving, climate change and violence also contribute to the need to move. Mobility is likely to increase in the coming decades, both due to permanent migration and increased temporary mobility, which is likely much more common. We outline three central questions regarding mobility and HIV treatment outcomes in SSA. First, it is unclear what aspects of mobility matter most for HIV care outcomes and if high‐risk mobility can be identified or predicted, which is necessary to facilitate targeted interventions for mobile populations. Second, it is unclear what groups are most vulnerable to mobility‐associated treatment interruption and other adverse outcomes. And third, it is unclear what interventions can improve HIV treatment outcomes for mobile populations.

Conclusions

Mobility is essential for people living with HIV in SSA. HIV treatment programmes and broader health systems must understand and adapt to human mobility, both to promote the rights and welfare of mobile people and to end the HIV pandemic.
Mobility and ART retention among men in Malawi: a mixed‐methods study
Authors: Thorp Marguerite , Bellos MacDaphton , Temelkovska Tijana , Mphande Misheck , Cornell Morna , Hubbard Julie , Choko Augustine , Coates Thomas J. , Hoffman Risa , Dovel Kathryn
Published: March 2023

Introduction

Mobility is associated with worse outcomes across the HIV treatment cascade, especially among men. However, little is known about the mechanisms that link mobility and poor HIV outcomes and what types of mobility most increase the risk of treatment interruption among men in southern Africa.

Methods

From August 2021 to January 2022, we conducted a mixed‐methods study with men living with HIV (MLHIV) but not currently receiving antiretroviral therapy (ART) in Malawi. Data collection was embedded within two larger trials (ENGAGE and IDEaL trials). We analysed baseline survey data of 223 men enrolled in the trials who reported being mobile (defined as spending ≥14 nights away from home in the past 12 months) using descriptive statistics and negative binomial regressions. We then recruited 32 men for in‐depth interviews regarding their travel experiences and ART utilization. We analysed qualitative data using constant comparative methods.

Results

Survey data showed that 34% of men with treatment interruptions were mobile, with a median of 60 nights away from home in the past 12 months; 69% of trips were for income generation. More nights away from home in the past 12 months and having fewer household assets were associated with longer periods out of care. In interviews, men reported that travel was often unplanned, and men were highly vulnerable to exploitive employer demands, which led to missed appointments and ART interruption. Men made major efforts to stay in care but were often unable to access care on short notice, were denied ART refills at non‐home facilities and/or were treated poorly by providers, creating substantial barriers to remaining in and returning to care. Men desired additional multi‐month dispensing (MMD), the ability to refill treatment at any facility in Malawi, and streamlined pre‐travel refills at home facilities.

Conclusions

Men prioritize ART and struggle with the trade‐offs between their own health and providing for their families. Mobility is an essential livelihood strategy for MLHIV in Malawi, but it creates conflict with ART retention, largely due to inflexible health systems. Targeted counselling and peer support, access to ART services anywhere in the country, and MMD may improve outcomes for mobile men.
Confirmatory Auditory Brainstem Responses Testing Results in Discordant Outcomes: Implications for Timely Care
Authors: Tunkel Alexandra E. , Gorelik Daniel , Behzadpour Hengameh K. , Rana Md Sohel , Ambrose Tracey , Kronzek Eve , Preciado Diego A. , Reilly Brian K.
Published: March 2023

Objectives

The purpose of this study is to evaluate for discrepancies in diagnostic auditory brainstem responses (ABR) between Children's National Hospital (CNH), a pediatric medical center, and outside facilities (OSF) that referred patients to CNH for confirmatory evaluation. Such discrepancies impact early hearing detection and intervention (EHDI) timelines.

Methods

A retrospective chart review was conducted from an internal database of patients who underwent diagnostic ABR from 2017 to 2021. Only patients with ABR results from both CNH and OSF were analyzed. Demographic data, external and internal test results, and intervention data were obtained. Hearing loss (HL) severity was graded on a scale of 0 to 8, where 0 indicated normal hearing and 8 indicated profound. Each ear was analyzed separately.

Results

Forty‐nine patients met the inclusion criteria, and each ear was evaluated separately. Median HL severity was 1.0 [0.0, 4.3] at CNH compared to 3.0 [1.8, 6] at OSF (p = 0.004). Forty‐seven ears (48.0%) showed lower severity at CNH. Twenty‐seven patients (55%) received hearing amplification devices. The median age at time of hearing intervention was 220 days.

Conclusion

Our results showed statistical significance in the median severity of HL between CNH and OSF. A substantial proportion (70%) of children in our dataset who received amplification via cochlear implant or hearing aids were shown to have discrepancies in ABR findings from CNH and OSF. These findings have implications with regards to the appropriate usage of health care resources and maintaining EDHI timelines.

Level of Evidence

4 (Retrospective Cohort Study) Laryngoscope, 133:3571–3574, 2023
Molecular Mobility of Polyrotaxane Surfaces Alleviates Oxidative Stress‐Induced Senescence in Mesenchymal Stem Cells
Authors: Masuda Hiroki , Arisaka Yoshinori , Hakariya Masahiro , Iwata Takanori , Yoda Tetsuya , Yui Nobuhiko
Published: March 2023

Polyrotaxane is a supramolecular assembly consisting of multiple cyclic molecules threaded by a linear polymer. One of the unique properties of polyrotaxane is molecular mobility, cyclic molecules moving along the linear polymer. Molecular mobility of polyrotaxane surfaces affects cell spreading, differentiation, and other cell‐related aspects through changing subcellular localization of yes‐associated proteins (YAPs). Subcellular YAP localization is also related to cell senescence derived from oxidative stress, which is known to cause cancer, diabetes, and heart disease. Herein, the effects of polyrotaxane surface molecular mobility on subcellular YAP localization and cell senescence following H2O2‐induced oxidative stress are evaluated in human mesenchymal stem cells (HMSCs) cultured on polyrotaxane surfaces with different molecular mobilities. Oxidative stress promotes cytoplasmic YAP localization in HMSCs on high‐mobility polyrotaxane surfaces; however, low‐mobility polyrotaxane surfaces more effectively maintain nuclear YAP localization, exhibiting lower senescence‐associated β‐galactosidase activity and senescence‐related gene expression and DNA damage than that seen with the high‐mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces regulates subcellular YAP localization, thereby protecting HMSCs from oxidative stress‐induced cell senescence. Applying the molecular mobility of polyrotaxane surfaces to implantable scaffolds can provide insights into the prevention and treatment of diseases caused by oxidative stress.
Automated assessment of necrosis tumor ratio in colorectal cancer using an artificial intelligence‐based digital pathology analysis
Authors: Ye Huifen , Ye Yunrui , Wang Yiting , Tong Tong , Yao Su , Xu Yao , Hu Qingru , Liu Yulin , Liang Changhong , Wang Guangyi , Zhao Ke , Fan Xinjuan , Cui Yanfen , Liu Zaiyi
Published: March 2023

Background

With the advance in digital pathology and artificial intelligence (AI)‐powered approaches, necrosis is proposed as a marker of poor prognosis in colorectal cancer (CRC). However, most previous studies quantified necrosis merely as a tissue type and patch‐level segmentation. Thus, it was worth exploring and validating the prognostic and predictive value of necrosis proportion with a pixel‐level segmentation in large multicenter cohorts.

Methods

A semantic segmentation model was trained with 12 tissue types labeled by pathologists. Segmentation was performed using the U‐net model with a subsequently derived necrosis tumor ratio (NTR). We proposed the NTR score (NTR‐low or NTR‐high) to evaluate the prognostic and predictive value of necrosis for disease‐free survival (DFS) and overall survival (OS) in the development (N = 443) and validation cohorts (N = 333) using 75% as a threshold.

Results

The 2‐category NTR was an independent prognostic factor and NTR‐low was associated with significant prolonged DFS (unadjusted HR for high vs. low 1.72 [95% CI 1.19–2.49] and 1.98 [1.22–3.23] in the development and validation cohorts). Similar trends were observed for OS. The prognostic value of NTR was maintained in the multivariate analysis for both cohorts. Furthermore, a stratified analysis showed that NTR‐high was a high risk with adjuvant chemotherapy for OS in stage II CRC (p = 0.047).

Conclusion

AI‐based pixel‐level quantified NTR has a stable prognostic value in CRC associated with unfavorable survival. Additionally, adjuvant chemotherapy provided survival benefits for patients with a high NTR score in stage II CRC.
Impact of built, social, and economic environments on adolescent obesity and related health behaviors
Authors: Prados María J. , Nicosia Nancy , Datar Ashlesha
Published: March 2023

Objective

This study aimed to estimate the effects of the built, social, and economic environments on adolescent obesity and related behaviors.

Methods

Exploiting quasi‐exogenous variation in military families' geographic location, this study estimated intent‐to‐treat models of the association between the assigned installation's county environments and adolescents' (mean age 13.5 years) self‐reported and model‐corrected BMI, overweight or obesity status, and self‐reported diet and exercise. Three indices for the built, social, and economic environments characterized county‐level environments (higher value implies more advantageous environments) based on 19 indicators. Multivariate linear and logistic models were estimated on the full sample (N = 1111) and on subsamples with greater exposure based on time (n = 682) and off‐installation residence (n = 604).

Results

Exposure to more advantageous built environments for more than 2 years was associated with lower probabilities of obesity (−0.18; 95% CI: −0.34 to −0.026) and overweight or obesity (−0.34; 95% CI: −0.56 to −0.12) and was associated with lower BMI z scores (−0.76; 95% CI: −1.45 to −0.02). Results for adolescents living off‐installation were similar. More advantageous built environments were also associated with lower consumption of unhealthy foods, but not with physical activity. Social and economic environments were not associated with any outcomes.

Conclusions

The built environment, but not social and economic environments, was a strong predictor of adolescents' BMI, overweight or obesity status, and eating behaviors.
Needs Assessment of Gender‐Affirming Face, Neck, and Voice Procedures and the Role of Gender Dysphoria
Authors: Ziltzer Ryan S. , Lett Elle , Su‐Genyk Peiyi , Chambers Tamara , Moayer Roxana
Published: March 2023

Objective

To assess the needs of transgender and nonbinary (TNB) adults for gender‐affirming face, neck, and voice procedures.

Study Design

Cross‐sectional survey.

Setting

Online, February to May 2022.

Methods

Primary outcomes included utilization of otolaryngologists and speech‐language pathologists; gender dysphoria felt from the face, neck, and voice self‐reported on a 0 to 10 numeric rating scale (0 = no dysphoria, 10 = unbearable); and desire for various gender‐affirming face, neck, and voice procedures. We used ordinal logistic and linear regression to assess relationships between site‐specific dysphoria and the desire for relevant procedures.

Results

TNB participants (N = 234) infrequently sought gender‐affirming care with speech‐language pathologists (23%), facial plastic surgeons (8%), or laryngologists (3%). Participants experienced the strongest dysphoria from the voice (median 7/10), jawline/chin (4/10), and neck (3.5/10). Transmasculine and nonbinary participants typically seeking masculinization (n = 83) frequently desired voice therapy (want = 35%, had = 8%). Transfeminine and nonbinary participants typically seeking feminization (n = 145) frequently desired voice therapy (want = 52%, had = 23%), chondrolaryngoplasty (want = 45%, had = 5%), and hair removal/electrolysis (want = 43%, had = 44%). Many desired at least 1 facial feminization surgery procedure (65%), especially mandible reduction (want = 42%, had = 3%), rhinoplasty (want = 41%, had = 1%), and forehead reduction (want = 37%, had = 4%). Dysphoria ratings were associated with desiring relevant procedures (p < .05 for all), notably voice therapy (odds ratio [OR] = 1.50), chondrolaryngoplasty (OR = 1.46), mandible reduction (OR = 1.38), rhinoplasty (OR = 1.59), and forehead reduction (OR = 1.82).

Conclusion

Gender dysphoria from the face, neck, and voice can be severe for TNB people and is associated with the desire for gender‐affirming procedures. The high demand yet low reported access to these procedures highlights the need for providers of gender‐affirming face, neck, and voice care.
Insecticide resistance compromises the control of Aedes aegypti in Bangladesh
Authors: Al‐Amin Hasan Mohammad , Gyawali Narayan , Graham Melissa , Alam Mohammad Shafiul , Lenhart Audrey , Hugo Leon E , Rašić Gordana , Beebe Nigel W , Devine Gregor J
Published: March 2023

BACKGROUND

With no effective drugs or widely available vaccines, dengue control in Bangladesh is dependent on targeting the primary vector Aedes aegypti with insecticides and larval source management. Despite these interventions, the dengue burden is increasing in Bangladesh, and the country experienced its worst outbreak in 2019 with 101 354 hospitalized cases. This may be partially facilitated by the presence of intense insecticide resistance in vector populations. Here, we describe the intensity and mechanisms of resistance to insecticides commonly deployed against Ae. aegypti in Dhaka, Bangladesh.

RESULTS

Dhaka Ae. aegypti colonies exhibited high‐intensity resistance to pyrethroids. Using CDC bottle assays, we recorded 2–24% mortality (recorded at 24 h) to permethrin and 48–94% mortality to deltamethrin, at 10× the diagnostic dose. Bioassays conducted using insecticide–synergist combinations suggested that metabolic mechanisms were contributing to pyrethroid resistance, specifically multi‐function oxidases, esterases, and glutathione S‐transferases. In addition, kdr alleles were detected, with a high frequency (78–98%) of homozygotes for the V1016G mutation. A large proportion (≤ 74%) of free‐flying and resting mosquitoes from Dhaka colonies survived exposure to standard applications of pyrethroid aerosols in an experimental free‐flight room. Although that exposure affected the immediate host‐seeking behavior of Ae. aegypti, the effect was transient in surviving mosquitoes.

CONCLUSION

The intense resistance characterized in this study is likely compromising the operational effectiveness of pyrethroids against Ae. aegypti in Dhaka. Switching to alternative chemical classes may offer a medium‐term solution, but ultimately a more sustainable and effective approach to controlling dengue vectors is required. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A cluster of heritable pulmonary arterial hypertension cases in a family with all three siblings carrying the same novel AQP1 c.273C>G variant‐a case report
Authors: Liang Kae‐Woei , Chang Sheng‐Kai , Chen Yu‐Wei , Tsai Wan‐Jane , Wang Kuo‐Yang
Published: March 2023

Approximately 25%–30% of patients diagnosed with idiopathic pulmonary arterial hypertension (PAH) have a clustered underlying Mendelian genetic cause and should be classified as heritable PAH (HPAH). The sixth World Symposium on Pulmonary Hypertension listed AQP1 as a PAH‐related gene. AQP1 and its protein product Aquaporin‐1 (AQP1) are found in abundance within pulmonary artery smooth muscle cells. Here, we report a family affected by HPAH with all three siblings carrying the same novel missense variant of AQP1 c.273C>G (p.Ile91Met). The youngest brother and the older sister both had dyspnea and edema and were diagnosed with HPAH about 10 years ago. In 2021, they received genetic tests that revealed all three siblings carried the same novel variant of AQP1 (c.273C>G). The brother in between these two siblings, although originally claimed to be asymptomatic, raised awareness. He then sought medical examination and confirmed the diagnosis of HPAH as well. This report on all three siblings carrying the same novel variant of AQP1 (c.273C>G) highlighted the importance of genetic testing and counseling for family members when PAH was first detected.
Difficult removal after bronchial filling of an endobronchial Watanabe spigot with N‐butyl‐2‐cyanoacrylate for intractable pneumothorax: A case report
Authors: Nakamura Tomoaki , Ro Shosei , Morita Chie , Kanomata Naoki , Kitamura Atsushi
Published: March 2023

A 52‐year‐old man developed a right pneumothorax during treatment for COVID‐19. In a previous case report concerning this patient, his recovery was achieved through implanting four endobronchial Watanabe spigots (EWS) in the right B1 and B3 in two phases and spraying N‐butyl‐2‐cyanoacrylate (NBCA). One year later, EWS removal was planned. He was intubated under bronchoscopic guidance, and the right upper lobe was observed. The right B1 and B3 inlets were found to be covered with granuloma. Despite the presence of a nylon thread for easy retrieval and partial debridement of the granulation, removal of the implanted EWS in the right B1 and B3 using grasping forceps, basket forceps, and two types of balloons under fluoroscopic guidance was challenging. NBCA spraying is a possible cause of foreign body granuloma formation. Therefore, careful consideration of the indications for the combined EWS‐NBCA procedure is necessary.
Emissions trading scheme and green development in China: Impact of city heterogeneity
Authors: Zhai Xueqi , An Yunfei , Shi Xunpeng , Cui Hongqiao
Published: March 2023

The emissions trading scheme (ETS) is a key policy tool for reducing carbon emissions and combating climate change but may cause unintended social‐economic consequences. Clarifying the role of city heterogeneity can contribute to improving ETS policy and informing green development roadmaps. Using panel data of 274 Chinese prefecture‐level cities, the heterogeneous impacts of ETS on city green development efficiency (CGDE) were assessed by the difference in difference in difference (DDD) method. The results show that: the ETS significantly advances China's CGDE, mainly through inducing cities' green innovation. More insightfully, the ETS policy has more significant positive effects on the cities in the eastern region, high economic development, resource abundance, and good environmental governance than otherwise. The study suggests that designing the ETS should incorporate the cities' heterogeneous characteristics to accelerate green development through green innovation and cover more regions and industries.
Acoustic Trapping: An Emerging Tool for Microfabrication Technology
Authors: Yin Chengying , Jiang Xingyu , Mann Stephen , Tian Liangfei , Drinkwater Bruce W.
Published: March 2023

The high throughput deposition of microscale objects with precise spatial arrangement represents a key step in microfabrication technology. This can be done by creating physical boundaries to guide the deposition process or using printing technologies; in both approaches, these microscale objects cannot be further modified after they are formed. The utilization of dynamic acoustic fields offers a novel approach to facilitate real‐time reconfigurable miniaturized systems in a contactless manner, which can potentially be used in physics, chemistry, biology, as well as materials science. Here, the physical interactions of microscale objects in an acoustic pressure field are discussed and how to fabricate different acoustic trapping devices and how to tune the spatial arrangement of the microscale objects are explained. Moreover, different approaches that can dynamically modulate microscale objects in acoustic fields are presented, and the potential applications of the microarrays in biomedical engineering, chemical/biochemical sensing, and materials science are highlighted alongside a discussion of future research challenges.
NIR‐II Imaging‐Guided Mitochondrial‐Targeting Organic Nanoparticles for Multimodal Synergistic Tumor Therapy
Authors: Yang Sha , Sun Bin , Liu Fen , Li Na , Wang Minghui , Wu Peixian , Wu Gui‐long , Fang Huilong , He Yuxuan , Zhou Wei , Xiao Hao , Tan Xiaofeng , Tang Li , Zhu Shoujun , Yang Qinglai
Published: March 2023

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial‐targeting phototheranostic system, FE‐T nanoparticles (FE‐T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE‐T NPs are engineered by encapsulating the near‐infrared (NIR) absorbed photosensitizer IR‐FE‐TPP within amphiphilic copolymer DSPE‐SS‐PEG‐COOH for high‐performing with simultaneous mitochondrial‐targeting, near‐infrared II (NIR‐II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR‐FE‐TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE‐T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial‐targeting with FE‐T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE‐T NPs provide an effective mitochondrial‐targeting phototheranostic nanoplatform for imaging‐guided tumor therapy.