bluuebunny/crossref_metadata_2025 huggingface dataset:
Munc13- and SNAP25-dependent molecular bridges play a key role in synaptic vesicle priming
Authors: Papantoniou Christos , Laugks Ulrike , Betzin Julia , Capitanio Cristina , Ferrero José Javier , Sánchez-Prieto José , Schoch Susanne , Brose Nils , Baumeister Wolfgang , Cooper Benjamin H. , Imig Cordelia , Lučić Vladan
Published: June 2023

Synaptic vesicle tethering, priming, and neurotransmitter release require a coordinated action of multiple protein complexes. While physiological experiments, interaction data, and structural studies of purified systems were essential for our understanding of the function of the individual complexes involved, they cannot resolve how the actions of individual complexes integrate. We used cryo–electron tomography to simultaneously image multiple presynaptic protein complexes and lipids at molecular resolution in their native composition, conformation, and environment. Our detailed morphological characterization suggests that sequential synaptic vesicle states precede neurotransmitter release, where Munc13-comprising bridges localize vesicles <10 nanometers and soluble
N
-ethylmaleimide–sensitive factor attachment protein 25–comprising bridges <5 nanometers from the plasma membrane, the latter constituting a molecularly primed state. Munc13 activation supports the transition to the primed state via vesicle bridges to plasma membrane (tethers), while protein kinase C promotes the same transition by reducing vesicle interlinking. These findings exemplify a cellular function performed by an extended assembly comprising multiple molecularly diverse complexes.
Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
Authors: Levin Solomon N. , Tomasini Michael D. , Knox James , Shirani Mahsa , Shebl Bassem , Requena David , Clark Jackson , Heissel Søren , Alwaseem Hanan , Surjan Rodrigo , Lahasky Ron , Molina Henrik , Torbenson Michael S. , Lyons Barbara , Migler Rachael D. , Coffino Philip , Simon Sanford M.
Published: June 2023

Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis. Hyperammonemic encephalopathy is a recurrent problem in these patients, and established treatments based on the assumption of liver failure are unsuccessful. We show that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased. We also demonstrate that the metabolites of these enzymes change as expected. Thus, hyperammonemic encephalopathy in FLC may require alternative therapeutics.
Single-shot optical neural network
Authors: Bernstein Liane , Sludds Alexander , Panuski Christopher , Trajtenberg-Mills Sivan , Hamerly Ryan , Englund Dirk
Published: June 2023

Analog optical and electronic hardware has emerged as a promising alternative to digital electronics to improve the efficiency of deep neural networks (DNNs). However, previous work has been limited in scalability (input vector lengthK≈ 100 elements) or has required nonstandard DNN models and retraining, hindering widespread adoption. Here, we present an analog, CMOS–compatible DNN processor that uses free-space optics to reconfigurably distribute an input vector and optoelectronics for static, updatable weighting and the nonlinearity—withK≈ 1000 and beyond. We demonstrate single-shot-per-layer classification of the MNIST, Fashion-MNIST, and QuickDraw datasets with standard fully connected DNNs, achieving respective accuracies of 95.6, 83.3, and 79.0% without preprocessing or retraining. We also experimentally determine the fundamental upper bound on throughput (∼0.9 exaMAC/s), set by the maximum optical bandwidth before substantial increase in error. Our combination of wide spectral and spatial bandwidths enables highly efficient computing for next-generation DNNs.
Guanidinium-based covalent organic framework membrane for single-acid recovery
Authors: Meng Qing-Wei , Wu Shaochun , Liu Mingjie , Guo Qing , Xian Weipeng , Zuo Xiuhui , Wang Sai , Yin Hong , Ma Shengqian , Sun Qi
Published: June 2023

Acids are extensively used in contemporary industries. However, time-consuming and environmentally unfriendly processes hinder single-acid recovery from wastes containing various ionic species. Although membrane technology can overcome these challenges by efficiently extracting analytes of interest, the associated processes typically exhibit inadequate ion-specific selectivity. In this regard, we rationally designed a membrane with uniform angstrom-sized pore channels and built-in charge-assisted hydrogen bond donors that preferentially conducted HCl while exhibiting negligible conductance for other compounds. The selectivity originates from the size-screening ability of angstrom-sized channels between protons and other hydrated cations. The built-in charge-assisted hydrogen bond donor enables the screening of acids by exerting host-guest interactions to varying extents, thus acting as an anion filter. The resulting membrane exhibited exceptional permeation for protons over other cations and for Cl
−
over SO
4
2−
and H

n

PO
4

(3-
n
)−

with selectivities up to 4334 and 183, respectively, demonstrating prospects for HCl extraction from waste streams. These findings will aid in designing advanced multifunctional membranes for sophisticated separation.
Desktop fabrication of monolithic soft robotic devices with embedded fluidic control circuits
Authors: Zhai Yichen , De Boer Albert , Yan Jiayao , Shih Benjamin , Faber Martin , Speros Joshua , Gupta Rohini , Tolley Michael T.
Published: June 2023

Most soft robots are pneumatically actuated and fabricated by molding and assembling processes that typically require many manual operations and limit complexity. Furthermore, complex control components (for example, electronic pumps and microcontrollers) must be added to achieve even simple functions. Desktop fused filament fabrication (FFF) three-dimensional printing provides an accessible alternative with less manual work and the capability of generating more complex structures. However, because of material and process limitations, FFF-printed soft robots often have a high effective stiffness and contain a large number of leaks, limiting their applications. We present an approach for the design and fabrication of soft, airtight pneumatic robotic devices using FFF to simultaneously print actuators with embedded fluidic control components. We demonstrated this approach by printing actuators an order of magnitude softer than those previously fabricated using FFF and capable of bending to form a complete circle. Similarly, we printed pneumatic valves that control a high-pressure airflow with low control pressure. Combining the actuators and valves, we demonstrated a monolithically printed electronics-free autonomous gripper. When connected to a constant supply of air pressure, the gripper autonomously detected and gripped an object and released the object when it detected a force due to the weight of the object acting perpendicular to the gripper. The entire fabrication process of the gripper required no posttreatment, postassembly, or repair of manufacturing defects, making this approach highly repeatable and accessible. Our proposed approach represents a step toward complex, customized robotic systems and components created at distributed fabricating facilities.
An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings
Authors: Kundrod Kathryn A. , Barra Maria , Wilkinson Alexis , Smith Chelsey A. , Natoli Mary E. , Chang Megan M. , Coole Jackson B. , Santhanaraj Akshaya , Lorenzoni Cesaltina , Mavume Celda , Atif Hira , Montealegre Jane Richards , Scheurer Michael E. , Castle Philip E. , Schmeler Kathleen M. , Richards-Kortum Rebecca R.
Published: June 2023

High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.
Closing the loop on adrenal health, dysfunction, and disease
Authors: Mohan Dipika R. , Lerario Antonio Marcondes
Published: June 2023

A wearable microdialysis device measures ultradian patterns of adrenal hormone secretion in humans at minute scale (Upton
et al
.).
In Vitro
and
In Vivo
Cysticidal Effects of
Carica Papaya
Cell Suspensions
Authors: Guzmán Cynthia , Villalobos Nelly , Ortiz Caltempa Anabel , Hernández Marisela , Núñez Guadalupe , Salazar Juan , Bobes Raúl José , Fragoso Gladis , Sciutto Edda , Villarreal María Luisa
Published: June 2023

Parasitic diseases are a major public health problem worldwide. Plant-derived products appear to be ideal candidates from a biotechnological perspective, being sustainable and environmentally friendly.
Topology and function of translocated EspZ
Authors: Haritan Nir , Bouman Etan Amse , Nandi Ipsita , Shtuhin-Rahav Raisa , Zlotkin-Rivkin Efrat , Danieli Tsafi , Melamed-Book Naomi , Nir-Keren Yael , Aroeti Benjamin
Published: June 2023

EspZ and Tir are essential virulence effectors of enteropathogenic
Escherichia coli
(EPEC). EspZ, the second translocated effector, has been suggested to antagonize host cell death induced by the first translocated effector, Tir (translocated intimin receptor). Another characteristic of EspZ is its localization to host mitochondria. However, studies that explored the mitochondrial localization of EspZ have examined the ectopically expressed effector and not the more physiologically relevant translocated effector. Here, we confirmed the membrane topology of translocated EspZ at infection sites and the involvement of Tir in confining its localization to these sites. Unlike the ectopically expressed EspZ, the translocated EspZ did not colocalize with mitochondrial markers. Moreover, no correlation has been found between the capacity of ectopically expressed EspZ to target mitochondria and the ability of translocated EspZ to protect against cell death. Translocated EspZ may have to some extent diminished F-actin pedestal formation induced by Tir but has a marked effect on protecting against host cell death and on promoting host colonization by the bacteria. Taken together, our results suggest that EspZ plays an essential role in facilitating bacterial colonization, likely by antagonizing cell death mediated by Tir at the onset of bacterial infection. This activity of EspZ, which occurs by targeting host membrane components at infection sites, and not mitochondria, may contribute to successful bacterial colonization of the infected intestine.

IMPORTANCE

EPEC is an important human pathogen that causes acute infantile diarrhea. EspZ is an essential virulence effector protein translocated from the bacterium into the host cells. Detailed knowledge of its mechanisms of action is, therefore, critical for better understanding the EPEC disease. We show that Tir, the first translocated effector, confines the localization of EspZ, the second translocated effector, to infection sites. This activity is important for antagonizing the pro-cell death activity conferred by Tir. Moreover, we show that translocated EspZ leads to effective bacterial colonization of the host. Hence, our data suggest that translocated EspZ is essential because it confers host cell survival to allow bacterial colonization at an early stage of bacterial infection. It performs these activities by targeting host membrane components at infection sites. Identifying these targets is critical for elucidating the molecular mechanism underlying the EspZ activity and the EPEC disease.
Host MOSPD2 enrichment at the parasitophorous vacuole membrane varies between
Toxoplasma
strains and involves complex interactions
Authors: Ferrel Abel , Romano Julia , Panas Michael W. , Coppens Isabelle , Boothroyd John C.
Published: June 2023

Toxoplasma gondii
is an obligate, intracellular parasite. Infection of a cell produces a unique niche for the parasite named the parasitophorous vacuole (PV) initially composed of host plasma membrane invaginated during invasion. The PV and its membrane (parasitophorous vacuole membrane [PVM]) are subsequently decorated with a variety of parasite proteins allowing the parasite to optimally grow in addition to manipulate host processes. Recently, we reported a proximity-labeling screen at the PVM–host interface and identified host endoplasmic reticulum (ER)-resident motile sperm domain-containing protein 2 (MOSPD2) as being enriched at this location. Here we extend these findings in several important respects. First, we show that the extent and pattern of host MOSPD2 association with the PVM differ dramatically in cells infected with different strains of
Toxoplasma
. Second, in cells infected with Type I RH strain, the MOSPD2 staining is mutually exclusive with regions of the PVM that associate with mitochondria. Third, immunoprecipitation and liquid chromatography tandem mass spectrometry (LC-MS/MS) with epitope-tagged MOSPD2-expressing host cells reveal strong enrichment of several PVM-localized parasite proteins, although none appear to play an essential role in MOSPD2 association. Fourth, most MOSPD2 associating with the PVM is newly translated after infection of the cell and requires the major functional domains of MOSPD2, identified as the CRAL/TRIO domain and tail anchor, although these domains were not sufficient for PVM association. Lastly, ablation of MOSPD2 results in, at most, a modest impact on
Toxoplasma
growth
in vitro
. Collectively, these studies provide new insight into the molecular interactions involving MOSPD2 at the dynamic interface between the PVM and the host cytosol.

IMPORTANCE

Toxoplasma gondii
is an intracellular pathogen that lives within a membranous vacuole inside of its host cell. This vacuole is decorated by a variety of parasite proteins that allow it to defend against host attack, acquire nutrients, and interact with the host cell. Recent work identified and validated host proteins enriched at this host–pathogen interface. Here, we follow up on one candidate named MOSPD2 shown to be enriched at the vacuolar membrane and describe it as having a dynamic interaction at this location depending on a variety of factors. Some of these include the presence of host mitochondria, intrinsic domains of the host protein, and whether translation is active. Importantly, we show that MOSPD2 enrichment at the vacuole membrane differs between strains indicating active involvement of the parasite with this phenotype. Altogether, these results shed light on the mechanism and role of protein associations in the host–pathogen interaction.
Uncharacterized and lineage-specific accessory genes within the
Proteus mirabilis
pan-genome landscape
Authors: Potter Robert F. , Zhang Kailun , Reimler Ben , Marino Jamie , Muenks Carol E. , Alvarado Kelly , Wallace Meghan A. , Westblade Lars F. , McElvania Erin , Yarbrough Melanie L. , Hunstad David A. , Dantas Gautam , Burnham Carey-Ann D.
Published: June 2023

Proteus mirabilis
is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike other Gram-negative bacteria,
P. mirabilis
may not exhibit significant intraspecies variation in gene content. However, there has not been a comprehensive analysis of large numbers of
P. mirabilis
genomes from various sources to support or refute this hypothesis. We performed comparative genomic analysis on 2,060
Proteus
genomes. We sequenced the genomes of 893 isolates recovered from clinical specimens from three large US academic medical centers, combined with 1,006 genomes from NCBI Assembly and 161 genomes assembled from Illumina reads in the public domain. We used average nucleotide identity (ANI) to delineate species and subspecies, core genome phylogenetic analysis to identify clusters of highly related
P. mirabilis
genomes, and pan-genome annotation to identify genes of interest not present in the model
P. mirabilis
strain HI4320. Within our cohort,
Proteus
is composed of 10 named species and 5 uncharacterized genomospecies.
P. mirabilis
can be subdivided into three subspecies; subspecies 1 represented 96.7% (1,822/1,883) of all genomes. The
P. mirabilis
pan-genome includes 15,399 genes outside of HI4320, and 34.3% (5,282/15,399) of these genes have no putative assigned function. Subspecies 1 is composed of several highly related clonal groups. Prophages and gene clusters encoding putatively extracellular-facing proteins are associated with clonal groups. Uncharacterized genes not present in the model strain
P. mirabilis
HI4320 but with homology to known virulence-associated operons can be identified within the pan-genome.

IMPORTANCE

Gram-negative bacteria use a variety of extracellular facing factors to interact with eukaryotic hosts. Due to intraspecies genetic variability, these factors may not be present in the model strain for a given organism, potentially providing incomplete understanding of host-microbial interactions. In contrast to previous reports on
P. mirabilis
, but similar to other Gram-negative bacteria,
P. mirabilis
has a mosaic genome with a linkage between phylogenetic position and accessory genome content.
P. mirabilis
encodes a variety of genes that may impact host-microbe dynamics beyond what is represented in the model strain HI4320. The diverse, whole-genome characterized strain bank from this work can be used in conjunction with reverse genetic and infection models to better understand the impact of accessory genome content on bacterial physiology and pathogenesis of infection.
Quantitative Proteomic Analysis of Outer Membrane Vesicles from Fusobacterium nucleatum Cultivated in the Mimic Cancer Environment
Authors: Zhang Xuqiang , Wang Yuxin , Fan Ruochen , Zhang Liying , Li Zhuting , Zhang Yanmei , Zheng Wei , Wang Lulu , Liu Baoquan , Quan Chunshan
Published: June 2023

F. nucleatum
is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. OMVs have been demonstrated to play key roles in pathogenesis by delivering toxins and other virulence factors to host cells.
Return to driving following surgery to the upper limb: a scoping review protocol
Authors: Rankin Carly Renee , Smith Simon
Published: June 2023

Introduction

Upper limb surgery is a common burden on the active and ageing population, often resulting in a transient state of functional impairment. Many activities of daily living can be affected, including ability to drive. Currently there are no guidelines regarding safe return to driving following upper limb surgery. This scoping review aims to systematically review the current literature on the topic of driving following surgery to the upper limb.

Methods and analysis

Informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Scoping Review extension guidelines, this protocol details the scoping review’s methodological and analytical approaches. The review will consider all primary and secondary source articles that examine return to driving following surgery to the upper limb, including the impact of orthoses on functional ability to drive. All studies will be included regardless of methodology and text and opinion pieces will also be considered. Studies conducted in any geographical location or setting will be included in the review. Systematic searches of scientific databases such as OVID (MEDLINE, EMBASE and Cochrane), NCBI (PubMed), Scopus, PsycINFO, EBSCOhost (CINAHL), Web of Science, Google Scholar and ProQuest will be conducted. In addition, relevant organisational websites, dissertations, theses from university repositories and grey literature will be included. Further articles will be identified by searching references of relevant studies. Studies conducted in English in any year will be included. Two independent reviewers will screen identified literature sources based on predetermined inclusion/exclusion criteria. Discrepancies will be resolved through discussion, therefore, negating the need for a third reviewer. Article data will be presented in tabular or graphical format along with a narrative summary.

Ethics and dissemination

Ethics approval is not required. Findings will be disseminated through professional networks, peer-reviewed publications and conference presentations.
Acupuncture for gait disturbance of patients with subacute and chronic stroke: a systematic review and meta-analysis protocol
Authors: Sun Zheng , Lin Yi-ren , Lu Meng-jiang , Huang Kai-yu , Sun Ke , Zhang Jian-bin
Published: June 2023

Introduction

Hemiparetic gait is one of the most common sequelae of a stroke. Acupuncture has shown potential in correcting hemiplegic gait patterns and improving motor function recovery after stroke. However, controversial findings and a lack of supportive evidence on the effectiveness of acupuncture for post-stroke hemiplegia. The intelligent gait analysis system provides a new perspective for the study of hemiparetic gait. This systematic review aims to collect relevant studies and critically evaluate the efficacy and safety of acupuncture in alleviating gait disturbance of post-stroke hemiplegia based on quantified gait parameters.

Methods and analysis

A comprehensive search of PubMed, Embase, Cochrane stroke group trials register, Cochrane Central Register of Controlled Trials, CINAHL, AMED, three Chinese databases (Chinese Biomedical Literatures database (CBM), National Knowledge Infrastructure (CNKI), and Wan fang Digital Periodicals), four trails registries (The WHO International Clinical Trials Registry Platform, The Chinese Clinical Trial Registry, The US National Institutes of Health Ongoing Trials Register, and The Australian New Zealand Clinical Trials Registry) will be conducted to identify randomised controlled trials of acupuncture for gait disturbance in post-stroke patients. No restrictions on language or publication status. The primary outcomes are gait temporospatial parameters (eg, step length, stride length, step width, step frequency (cadence), walking speed, etc), and gait kinematic parameters (eg, hip peak flex/extend angle, knee peak flex/extend angle, ankle peak dorsi/plantar-flexion angle, etc). We will assess bias using the approach recommended by the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis will be conducted to synthesise the evidence for each outcome measure. The χ2test and I2statistic will be used for assessing heterogeneity between studies.

Ethics and dissemination

No ethical approval is needed because no primary data is collected. Scientific conferences or peer-reviewed journals will publish the findings.

PROSPERO registration number

CRD42022384348.
Automated catheter segmentation and tip detection in cerebral angiography with topology-aware geometric deep learning
Authors: Ghosh Rahul , Wong Kelvin , Zhang Yi Jonathan , Britz Gavin W , Wong Stephen T C
Published: June 2023

Background

Visual perception of catheters and guidewires on x-ray fluoroscopy is essential for neurointervention. Endovascular robots with teleoperation capabilities are being developed, but they cannot ‘see’ intravascular devices, which precludes artificial intelligence (AI) augmentation that could improve precision and autonomy. Deep learning has not been explored for neurointervention and prior works in cardiovascular scenarios are inadequate as they only segment device tips, while neurointervention requires segmentation of the entire structure due to coaxial devices. Therefore, this study develops an automatic and accurate image-based catheter segmentation method in cerebral angiography using deep learning.

Methods

Catheters and guidewires were manually annotated on 3831 fluoroscopy frames collected prospectively from 40 patients undergoing cerebral angiography. We proposed a topology-aware geometric deep learning method (TAG-DL) and compared it with the state-of-the-art deep learning segmentation models, UNet, nnUNet and TransUNet. All models were trained on frontal view sequences and tested on both frontal and lateral view sequences from unseen patients. Results were assessed with centerline Dice score and tip-distance error.

Results

The TAG-DL and nnUNet models outperformed TransUNet and UNet. The best performing model was nnUNet, achieving a mean centerline-Dice score of 0.98 ±0.01 and a median tip-distance error of 0.43 (IQR 0.88) mm. Incorporating digital subtraction masks, with or without contrast, significantly improved performance on unseen patients, further enabling exceptional performance on lateral view fluoroscopy despite not being trained on this view.

Conclusions

These results are the first step towards AI augmentation for robotic neurointervention that could amplify the reach, productivity, and safety of a limited neurointerventional workforce.
Optimising messages and images for e-cigarette warnings
Authors: Lazard Allison J , Ebrahimi Kalan Mohammad , Nicolla Sydney , Hall Marissa G , Ribisl Kurt M , Sheldon Jennifer Mendel , Whitesell Callie , Queen Tara L , Brewer Noel T
Published: June 2023

Background

The US Food and Drug Administration (FDA) requires electronic cigarettes (e-cigarettes) to have a single addiction warning, but many other health harms are associated with vaping and warnings grow stale over time. We aimed to develop new warning messages and images to discourage e-cigarette use.

Methods

Participants were 1629 US adults who vaped or smoked. We randomised each participant to evaluate 7 of 28 messages on newly developed
warning themes
(metals exposure, DNA mutation, cardiovascular problems, chemical exposure, lung damage, impaired immunity, addiction), and the current FDA-required warning (total of 8 messages). Then, participants evaluated images of hazards (eg, metal), internal harms (eg, organ damage) or people experiencing harms.

Results

Regarding intended effects, new warning themes all discouraged vaping more than the current FDA-required warning (all p<0.001), led to greater negative affect (all p<0.001) and led to more anticipated social interactions (all p<0.001). The most discouraging warnings were about toxic metals exposure. Regarding unintended effects, the new themes led to more stigma against people who vape (6 of 7 themes, p<0.001) and led to a greater likelihood of thinking vaping is more harmful than smoking (all 7 themes, p<0.001), although unintended effects were smaller than intended effects. Images of harms (internal or people experiencing) discouraged vaping more than images of hazards (all p<0.001).

Discussion

Vaping warning policies should communicate a broader range of hazards and harms, beyond addiction, to potentially increase awareness of health harms. Images of internal harm or people experiencing harms may be particularly effective at discouraging vaping.
Protecting and restoring habitats to benefit freshwater biodiversity
Authors: Piczak Morgan L. , Perry Denielle , Cooke Steven J. , Harrison Ian , Benitez Silvia , Koning Aaron , Peng Li , Limbu Peter , Smokorowski Karen E. , Salinas-Rodriguez Sergio , Koehn John D. , Creed Irena F.
Published: June 2023

Freshwater biodiversity is under great threat across the globe as evidenced by more severe declines relative to other types of ecosystems. Some of the main stressors responsible for these concerning trends is habitat fragmentation, degradation, and loss stemming from anthropogenic activities, including energy production, urbanization, agriculture, and resource extraction. Habitat protection and restoration both play an integral role in efforts to save freshwater biodiversity and associated ecosystem services from further decline. In this paper, we summarize the sources of threats associated with habitat fragmentation, degradation, and loss and then outline response options to protect and restore freshwater habitats. Specific response options are to legislate the protection of healthy and productive freshwater ecosystems, prioritize habitats for protection and restoration, enact durable protections, conserve habitat in a coordinated and integrated manner, engage in evidence-based restoration using an adaptive management approach, ensure that potential freshwater habitat alterations are mitigated or off-set, and future-proof protection and restoration actions. Such work should be done through a lens that engages and involves local community members. We identify three broad categories of obstacles that could arise during the implementation of the response options outlined: (a) scientific (e.g., inaccessible data or uncertainties), (b) institutional and management (e.g., capacity issues or differing goals across agencies), and (c) social and political (e.g., prioritizing economic development over conservation initiatives). The protection and restoration of habitats is key to Bend the Curve for freshwater biodiversity, with a comprehensive, connected, and coordinated effort of response options needed to protect intact habitats and restore fragmented, degraded, and lost habitats and the biodiversity and ecosystem services that they support.
ON THE CLASSICAL INTEGRAL OF FRACTAL FUNCTIONS
Authors: PRIYANKA T. M. C. , SERPA C. , GOWRISANKAR A.
Published: June 2023

In this paper, the integral of classical fractal interpolation function (FIF) and A-fractal function is explored for both the cases of constant and variable scaling factors. The definite integral for the classical FIF in the closed interval of [Formula: see text] is estimated. The novel notion of affine-quadratic FIF is introduced and integrated for both constant and variable scaling factors. It is demonstrated that its integral is not an affine-quadratic FIF, however it is a FIF. Similarly, by choosing the vertical scaling factors as constants and variables, A-fractal function is integrated. Further, by assuming certain condition on the block matrix, it is shown that like the original A-fractal function its integral is also an attractor for the iterated function system.
Artifact Evaluation for ACM TRETS Papers Submitted from the FPT Journal Track
Authors: Leeser Miriam
Published: June 2023

Authors of papers that were accepted to ACM TRETS via the FPT 2022 journal track had the option of participating in Artifact Evaluation (AE). Four papers from this track volunteered to participate in the AE process. All of these papers have been awarded badges from ACM as described below.
Cascading Degradations Artificially Improving the Lifetime of Li-ion Full Cells using DMC-based Highly Concentrated Electrolyte
Authors: Meunier V. , Capone F. , Dedryvère R. , Grimaud A.
Published: June 2023

The deployment of energy dense Ni-rich NMC (LiNixMnyCozO2 with x > 0.8) in Li-ion batteries is hampered by a poor interfacial stability above 4.2 V. Among the strategies to mitigate this instability, highly concentrated electrolytes (HCE) have shown a promising resilience at high potential. In this work, we demonstrate that although cells using HCE experience low capacity fading compared to conventional carbonate based-electrolyte, HCE does not prevent oxidation of dimethylcarbonate (DMC) at high potential. Even worse, this phenomenon cannot be fully offset by lithium intercalation at the negative electrode and eventually leads to lithium plating that precipitates the cell end of life. To circumvent lithium plating, cycling at high temperature is shown to build a more passivating solid electrolyte interphase (SEI); while promising at first, the lithium losses associated with the SEI formation trigger a jump of graphite staging. Only replacing DMC by ethyl carbonate (EC) solvent reduces efficiently the parasitic oxidation and prevents capacity rollover. This work, by the use of adapted testing protocols and analysis workflows, provides the necessary understanding to open new routes for tackling parasitic reaction at high voltage in Li-ion batteries, which including mastering of SEI formation conditions and the use of appropriate solvent.
Research journey into multiple-sensor theory
Authors: Yu Jerry
Published: June 2023

In 1998, I was asked by the American Physiological Society to review a book written by Dr. Michael de Burgh Daly, Peripheral Arterial Chemoreceptors and Respiratory-Cardiovascular Integration. Inspired by this work, I came to appreciate how researchers in the later stages of their careers and who provide a detailed review of their experimental approach might effectively contribute to science, especially to the benefit of young scientists (Yu J. The Physiologist 41: 231, 1998.). This article is written in that vein. Over several decades of intensive investigation of cardiopulmonary reflexes, focused on the sensory receptors, my colleagues and I advanced a novel multiple-sensor theory (MST) to explain the role of the vagal mechanosensory system. Described here is our research journey through various stages of developing MST and the process of how the problem was identified, approached, and tackled. MST redefines conventional mechanosensor doctrines and is supported by new studies that clarify a century of research data. It entails reinterpretation of many established findings. Hopefully, this article will benefit young scientists, such as graduate and postdoctoral students in the cardiopulmonary sensory research field.
Temporal and Spatial Evolution Mechanisms of the Water-Conducting Fractured Zone of Overlying Strata in the Kongzhuang Coal Mine
Authors: Pei-ding Zhang , Chao-shang Sun , Xuan Fan , Song-tao Li , Long-jing Wang , Zheng-zheng Cao
Published: June 2023

Kongzhuang coal mine of Shanghai Datun Energy Resources Co., Ltd. is a typical deep coal mine in eastern China. The mining disturbance of working face in deep coal mine leads to the fracture and movement of overlying strata and the damage of the aquifer in overlying strata, thereby causing water inrush disaster and posing a serious threat to the safety production in coal mine. Therefore, the temporal and spatial evolution mechanism of the water-conducting fractured zone of overlying strata in the Kongzhuang coal mine is researched systematically in this paper. Especially, the hydro-geological conditions and mining conditions in the Kongzhuang coal mine are analyzed; on this basis, the fracture and movement of overlying strata are simulated by physical similarity simulation test, and the temporal and spatial evolution rule of overlying strata in the Kongzhuang coal mine is obtained. Besides, the development height of “two zones” is measured by double-end water shutoff detection method, and the risk assessment for the water inrush disaster of the coal seam roof is carried out in the Kongzhuang coal mine. The research achievements in this paper indicate that the water-conducting channel formed in the mining process of #7 coal seam is the most important water-filling channel. Quaternary aquifer water recharges the mine indirectly through the bedrock aquifer, and the sandy mudstone with large thickness is the key layer to control the development of a water-conducting fracture zone. Meanwhile, the height of the caving zone is 26.7 m, about 8.3 times of mining height, and the height of the fracture zone is 68.3 m, approximately equal to 16.26 of the mining height. The results of #1 and #2 borehole leakages in the double-end water shutoff detection method show that the height of the water-conducting fractured zone is 63.70 m-65.27 m, and the split-to-mining ratio is 15.17-15.54. The water inrush risk of the coal seam roof shows that most of the 7436 working face is in the transition zone, and a small area around the cutting hole of the working face is in the relatively dangerous zone. Therefore, the innovation of this paper is that the temporal and spatial evolution mechanism of the water-conducting fractured zone of overlying strata in the Kongzhuang coal mine is revealed, which provides the theoretical guidance for the prediction and prevention of water inrush disaster in the coal mine with the similar mining conditions.
How to Improve the Efficiency of Check-In Counter: A Counter-Sharing Method
Authors: Yang Shao-Peng , Tang Tie-Qiao , Wang Tao , Chen Liang
Published: June 2023

Improving the efficiency of check-in counters is a significant concern for airport operation management departments and airline companies. However, the existing studies mainly optimize the counter allocation based on the number of counters and airport demands, which needs more exploration on improving the utilization rate of check-in counters under the condition of unchanged resource allocation. In this paper, we propose a counter-sharing method to improve check-in efficiency by sharing the idle check-in counters in the adjacent check-in area. In the proposed counter-sharing method, we first define the passenger’s total walking distance and waiting time for queues as the metrics, then reassign the check-in areas and adjust the internal departure sequence of flights to maximize the counter-sharing rate. The numerical results indicate that the proposed counter-sharing method can improve the efficiency of check-in counters and reduce the passenger’s total walking distance and waiting time in the queue during the check-in process, which can enhance the airport’s operation efficiency and competitiveness.
An Overview of Nanomaterial Applications in Pharmacology
Authors: Roy Madhura , Roy Arpita , Rustagi Sarvesh , Pandey Neha
Published: June 2023

Nanotechnology has become one of the most extensive fields of research. Nanoparticles (NPs) form the base for nanotechnology. Recently, nanomaterials (NMs) are widely used due to flexible chemical, biological, and physical characteristics with improved efficacy in comparison to bulk counterparts. The significance of each class of NMs is enhanced by identifying their properties. Day by day, there is an emergence of various applications of NMs, but the toxic effects associated with them cannot be avoided. NMs demonstrate therapeutic abilities by enhancing the drug delivery system, diagnosis, and therapeutic effects of numerous agents, but determining the benefits of NMs over other clinical applications (disease‐specific) or substances is an ongoing investigation. This review is aimed at defining NMs and NPs and their types, synthesis, and pharmaceutical, biomedical, and clinical applications.
The Regulation Network of Glycerolipid Metabolism as Coregulators of Immunotherapy-Related Myocarditis
Authors: Yang Xiguang , Duan Xiaopeng , Xia Zhenglin , Huang Rui , He Ke , Xiang Guoan
Published: June 2023

Background. To date, immunotherapy for patients with malignant tumors has shown a significant association with myocarditis. However, the mechanism of metabolic reprogramming changes for immunotherapy-related cardiotoxicity is still not well understood. Methods. The CD45+ single-cell RNA sequencing (scRNA-seq) of the Pdcd1-/-Ctla4+/- and wild-type mouse heart in GSE213486 was downloaded to demonstrate the heterogeneity of immunocyte atlas in immunotherapy-related myocarditis. The liquid chromatography–tandem mass spectrometry (LC-MS/MS) spectrum metabolomics analysis detects the metabolic network differences. The drug prediction, organelle level interaction, mitochondrial level regulatory network, and phosphorylation site prediction for key regulators have also been screened via multibioinformatics analysis methods. Results. The scRNA analysis shows that the T cell is the main regulatory cell subpopulation in the pathological progress of immunotherapy-related myocarditis. Mitochondrial regulation pathway significantly participated in pseudotime trajectory- (PTT-) related differential expressed genes (DEGs) in the T cell subpopulation. Additionally, both the gene set enrichment analysis (GSEA) of PTT-related DEGs and LC-MS/MS metabolomics analysis showed that mitochondrial-regulated glycerolipid metabolism plays a central role in metabolic reprogramming changes for immunotherapy-related cardiotoxicity. Finally, the hub-regulated protease of diacylglycerol kinase zeta (Dgkz) was significantly identified and widely played various roles in glycerolipid metabolism, oxidative phosphorylation, and lipid kinase activation. Conclusion. Mitochondrial-regulated glycerolipid metabolism, especially the DGKZ protein, plays a key role in the metabolic reprogramming of immunotherapy-related myocarditis.
Effect of Fluconazole on the Pharmacokinetics of Pyrotinib Maleate: A Single-Center, Open, Single-Dose, Self-Controlled Study in Healthy Chinese Participants
Authors: Song Yuanming , Zhang Wenyu , Chen Peng , Liang Rui , Zhao Hengli , Wen Qing
Published: June 2023

What Is Known and Objective. Pyrotinib maleate, also known as pyrotinib, is an irreversible dual receptor tyrosine kinase inhibitor that primarily targets the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Cytochrome P450 3A4 (CYP3A4) enzyme mainly catalyzes pyrotinib, and its metabolism is influenced apparently by CYP3A4 strong inhibitor, but the effect of CYP3A4 moderate inhibitor is still unclear as a moderate inhibitor of CYP3A4 enzyme. This study evaluated the effect of fluconazole, a widespread antifungal medication, on the pharmacokinetics and safety tolerance of pyrotinib. Methods. This study was an open, single-dose, and self-controlled clinical trial. Eighteen healthy Chinese participants were enrolled in this study. All participants were administered fluconazole on days 6–18 and pyrotinib on days 1 and 9. The maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the concentration–time curve from time 0 to the last measurable concentration (AUC0−t), area under the concentration–time curve from time 0 extrapolated to infinity (AUC0−∞), terminal elimination half-life (t1/2), apparent volume of distribution (Vz/F), and apparent clearance (CL/F) were calculated using WinNonlin software (version 8.1). Safety tolerance was assessed throughout the process. Results and Discussion. Compared with the single administration of pyrotinib, the exposure level was enhanced significantly after the coadministration of pyrotinib and fluconazole. The geometric mean ratios (pyrotinib + fluconazole/pyrotinib alone) of Cmax, AUC0−t, and AUC0−∞ were 2.16, 3.6, and 3.5, respectively. The parameter of t1/2 is 14.16 h and 24.03 h, and CL/F is 275.06 L/h and 78.42 L/h, for pyrotinib alone and with fluconazole. No serious adverse events were reported in this trial, and no participant withdrew from the trial because of adverse events. What Is New and Conclusion. The PK profile of pyrotinib, a CYP3A4 substrate, was significantly influenced by fluconazole, with increased exposure levels and prolonged t1/2. Dosage adjustment is suggested for the clinical application of pyrotinib when coadministered with fluconazole or other CYP3A4 inhibitors/inducers.
Mechanical Behavior of Chain-Link Wire Nets under Pressure from a Warhead: Quasistatic Experiments and Simulations
Authors: Wang Min , Zhou Shuai , Huang Qilin
Published: June 2023

Wire nets woven from high-strength steel wires have been used as applique armor against attack by short-range weapons. In this study, the mechanical behavior of chain-link wire nets under pressure from a warhead was investigated by quasistatic experiments and simulations. First, the new rig, the warhead device, and the wire nets were designed; pressure tests were conducted; and the deformation, fracture of the wire nets, and pressure force vs. displacement curves were obtained and analyzed. Then, the numerical approach and Finite element (FE) model were developed, considering the contacts between the steel wires in the inner connections, the contacts between the warhead and the mesh of the wire nets, and the fracture of the steel wire material. By comparison with the experimental data, the numerical approach and FE model are shown to be reliable in predicting the behavior of the wire nets under pressure from a warhead. Finally, the parameters of the wire net size and the mesh angles were further investigated by using the validated numerical approach and FE model, and suggestions for the initial design of the wire nets are discussed.
Refractory Immune Thrombocytopenic Purpura with Abdominal Splenosis: A Complex Case
Authors: Mort Joseph F. , Tran Danh T. , Dougherty Sean C. , Zielinski Robert , Williams Michael D. , Davidson Kelly M.
Published: June 2023

Immune thrombocytopenia (ITP) is an acquired thrombocytopenia resulting from immune-mediated platelet destruction via antiplatelet antibodies and T cells. Medical management of ITP includes corticosteroids and multiple other adjunct therapies, with splenectomy generally being reserved for severe, refractory cases. In this clinical case report, we describe the evaluation of a 35-year-old male with a history of prior traumatic splenic injury who presented to the emergency department endorsing easy bruising and a petechial rash, ultimately found to have severe thrombocytopenia. The patient was diagnosed with primary ITP that proved to be refractory to a number of first- and second-line medical therapies. His course was complicated by the presence of abdominal splenosis discovered at the time of planned splenectomy and intra-abdominal hemorrhage requiring splenic artery embolization thereafter. To our knowledge, this is one of few published cases of ITP complicated by abdominal splenosis, highlighting the need to consider splenosis and the presence of accessory splenic tissue in cases of refractory ITP.
Supplementary Table 1 from Area Deprivation Index in Patients with Invasive Lobular Carcinoma of the Breast: Associations with Tumor Characteristics and Outcomes
Authors: Kaur Mandeep , Patterson Anne , Molina-Vega Julissa , Rothschild Harriet , Clelland Elle , Ewing Cheryl A. , Mujir Firdows , Esserman Laura J. , Olopade Olufunmilayo I. , Mukhtar Rita A.
Published: June 2023

Supplementary Table 1. ILC patient and tumor characteristics, including cases with missing data.