bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intelligent Setpoint Optimization for a Range Extender Hybrid Electric Vehicle With Opposed Piston Engine
Authors: Drallmeier Joseph A. , Nazari Shima , Solbrig Charles , Middleton Robert , Siegel Jason 
Published: October 2023

Abstract
This paper presents the exploration and optimization of a hybridized opposed piston (OP) engine. In this work, the exhaust crankshaft lead (ECL) is introduced as a controllable parameter in the hybridized OP engine enabled by eliminating the conventional geartrain linking the two crankshafts of an OP engine. This allows for variation in the effective compression and expansion ratio of the engine, along with scavenging performance. This novel control actuator as well as the adjustable speed and load setpoint in a series hybrid OP engine powertrain architecture necessitates an intensive calibration effort to realize any possible efficiency improvements. However, the OP engine within this series hybrid powertrain does not need to operate in highly transient conditions, but rather its operating point is fixed or slowly varying. This property permits the use of online calibration techniques. After manually sweeping speed and ECL values at two power setpoints, the use of an extremum-seeking type intercycle optimization algorithm to optimize the operating setpoint is validated, showing that near optimal speed and ECL setpoints can be selected despite the relatively flat operating map of the OP engine.
Exploring Physical Educators’ Self-Efficacy to Teach Students With Disabilities in General Physical Education
Authors: Nowland Lindsey A. 
Published: October 2023

The purpose of this study was to explore the ways in which in-service physical education teachers construct their self-efficacy beliefs toward teaching students with disabilities in general physical education classes. Using a qualitative descriptive approach situated within self-efficacy theory, data were collected via semistructured audio-recorded interviews with 16 in-service physical educators. Three interrelated themes were constructed: (a) The more I do it, the better I feel: the importance of professional experiences; (b) I’ve learned from others: the influence of colleagues; and (c) Being in the general educational setting is a challenge: the impact of contextual factors. Findings supported the influence of the four sources of self-efficacy (i.e., mastery experience, vicarious experience, social persuasion, and affective and physiological state), in addition to potential contextual factors (i.e., class sizes and availability of hands-on support), impacting participants’ self-efficacy to teach students with disabilities in general physical education classes.
IL-23 receptor signaling licenses group 3-like innate lymphoid cells to restrict a live-attenuated oral Chlamydia vaccine in the gut
Authors: He Ying , Wang Yihui , He Rongze , Abdelsalam Ahmed Mohamed , Zhong Guangming 
Published: October 2023

ABSTRACT

An IFNγ-susceptible mutant of
Chlamydia muridarum
is attenuated in pathogenicity in the genital tract and was recently licensed as an
intr
acellular
O
ral vaccine
v
ector or intrOv. Oral delivery of intrOv induces transmucosal protection in the genital tract, but intrOv itself is cleared from the gut (without shedding any infectious particles externally) by IFNγ from group 3-like innate lymphoid cells (ILC3s). We further characterized the intrOv interactions with ILC3s in the current study, since the interactions may impact both the safety and efficacy of intrOv as an oral Chlamydia vaccine. Intracolonic inoculation with intrOv induced IFNγ that in return inhibited intrOv. The intrOv-IFNγ interactions were dependent on RORγt, a signature transcriptional factor of ILC3s. Consistently, the transfer of oral intrOv-induced ILC3s from RORγt-GFP reporter mice to IFNγ-deficient mice rescued the inhibition of intrOv. Thus, IFNγ produced by intrOv-induced ILC3s is likely responsible for inhibiting intrOv, which is further supported by the observation that oral intrOv did induce significant levels of IFNγ-producing LC3s (IFNγ
+
ILC3s). Interestingly, IL-23 receptor knockout (IL-23R
−/−
) mice no longer inhibited intrOv, which was accompanied by reduced colonic IFNγ. Transfer of oral intrOv-induced ILC3s rescued the IL-23R
−/−
mice to inhibit intrOv, validating the dependence of ILC3s on IL-23R signaling for inhibiting intrOv. Clearly, intrOv induces intestinal IFNγ
+
ILC3s for its own inhibition in the gut, which is facilitated by IL-23R signaling. These findings have provided a mechanism for ensuring the safety of intrOv as an oral Chlamydia vaccine and a platform for investigating how oral intrOv induces transmucosal protection in the genital tract.
Nonadditive functional interactions between ligand-binding sites of the multidrug efflux pump AdeB from
Acinetobacter baumannii
Authors: Leus Inga V. , Roberts Sean R. , Trinh Anhthu , W. Yu Edward , Zgurskaya Helen I. 
Published: October 2023

ABSTRACT

Multidrug efflux is one of the major mechanisms of antibiotic resistance identified in clinical isolates of the human pathogen
Acinetobacter baumannii
. The multiple antibiotic resistance in this species is often enabled by the overproduction of the tripartite efflux pump AdeABC. In this pump, AdeB is the inner membrane transporter from the resistance-nodulation-division (RND) superfamily of proteins, which is responsible for the recognition and efflux of multiple structurally unrelated compounds. Like other RND transporters, AdeB is a trimeric protein with ligand-binding sites located in the large periplasmic domains. Previous structural studies, however, highlighted the uniqueness of AdeB interactions with ligands. Up to three ligand molecules were bound to one protomer of AdeB, mapping its substrate translocation path. In this study, we introduced single and double substitutions in the identified ligand-binding sites of AdeB. Our results show that the mechanism of substrate translocation by AdeB is different from that of other characterized RND transporters and that the functional interactions between the sites are nonadditive. We identified AdeB mutants with both the loss and the gain of antibiotic susceptibility phenotypes, as well as AdeB mutations making
A. baumannii
cells overproducing such pump variants even more susceptible to multiple antibiotics than efflux-deficient cells.

IMPORTANCE

Multidrug efflux pumps of the resistance-nodulation-division superfamily of proteins are important contributors to various aspects of bacterial physiology and antibiotic resistance. Studies of the best-characterized model transporter AcrB from
Escherichia coli
suggested that these transporters operate by a functional rotation mechanism in which various substrates bind to at least two different binding sites. This study suggests that the mechanism of AdeB is distinct and that the binding sites in this transporter are functionally linked.
Contact sites between host organelles and pathogens: boon or bane?
Authors: Mehra Chahat , Pernas Lena 
Published: October 2023

ABSTRACT

A microbe and its host are in constant communication. An emerging platform for direct communication is the membrane contact sites that form between several pathogens and host organelles. Here, we review our progress on the molecular mechanisms underlying contact sites between host mitochondria and the human parasite
Toxoplasma gondii
. We discuss open questions regarding their function during infection as well as those formed between the host endoplasmic reticulum and
Toxoplasma
.
Surveillance for rat hepatitis E in wastewater networks, Italy
Authors: Palombieri Andrea , Di Profio Federica , Sarchese Vittorio , Fruci Paola , Suffredini Elisabetta , Martella Vito , Veneri Carolina , Bonanno Ferraro Giusy , Mancini Pamela , La Rosa Giuseppina , Di Martino Barbara 
Published: October 2023

ABSTRACT
Rat hepevirus is an emerging zoonotic pathogen associated with human hepatitis and distantly related to the hepatitis E virus. By using broadly reactive primers for hepevirus, we detected viral RNA in 68/155 (43.9%) of sewage specimens collected from 14 wastewater treatment plants serving about half of the population of Abruzzo, Italy. On sequence analysis, the 68 strains showed 79.0%–91.6% identities to reference sequences of rodent and human origin, segregating in different genetic groups with a clear geographic/wastewater treatment plant (WWTP)-related pattern.

IMPORTANCE
Hepatitis E virus (HEV) infection constitutes a significant health problem worldwide. In recent years, in addition to the zoonotic HEV3 and HEV4, emerging highly divergent hepevirus of rat origin (rat HEV [RHEV]) has been associated with human acute and chronic hepatitis. As environmental surveillance can be a complementary tool to explore emerging viruses of human and rodent origin, we investigated the epidemiology and the genetic variability of RHEV targeting 14 wastewater treatment plants in an Italian geographic area considered a hot spot for HEV infection in humans. Our results revealed that RHEV is a significant component of the wastewater microbiota with viral RNA detected in 43.9% of the specimens tested, adding further evidence to the need to investigate more in depth the real burden of RHEV infections in humans.
KCNV2-associated retinopathy: genotype–phenotype correlations –KCNV2study group report 3
Authors: de Guimaraes Thales A C , Georgiou Michalis , Robson Anthony G , Fujinami Kaoru , Vincent Ajoy , Nasser Fadi , Khateb Samer , Mahroo Omar A , Pontikos Nikolas , Vargas Maurício E , Thiadens Alberta A H J , Carvalho Emanuel R de , Nguyen Xuan-Than-An , Arno Gavin , Fujinami-Yokokawa Yu , Liu Xiao , Tsunoda Kazushige , Hayashi Takaaki , Jiménez-Rolando Belén , Martin-Merida Maria Inmaculada , Avila-Fernandez Almudena , Salas Ester Carreño , Garcia-Sandoval Blanca , Ayuso Carmen , Sharon Dror , Kohl Susanne , Huckfeldt Rachel M , Banin Eyal , Pennesi Mark E , Khan Arif O , Wissinger Bernd , Webster Andrew R , Heon Elise , Boon Camiel J F , Zrenner Eberhard , Michaelides Michel 
Published: October 2023

Background/aimsTo investigate genotype–phenotype associations in patients withKCNV2retinopathy.MethodsReview of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination ofKCNV2variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared.ResultsNinety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants.ConclusionsPatients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials.
Preliminary Consequences of Blood Pressure Management and Blood Homocysteine Levels with Perindopril in Newly Diagnosed Hypertensive Patients in the Vietnamese Population
Authors: Kim Tran Son , Truong An Bao , Nguyen Phi Hoang , Ngo Toan Hoang , Vu Tuyen Long , Dang Tran Khoa Dang , Vo Phuong Minh , Nguyen Bao The , Le Trong Huynh Tuong , Nguyen Kien Trung , Tran Hung Do 
Published: October 2023

Background. Perindopril is an ACE inhibitor that aids in both blood pressure regulation and homocysteine reduction. Objectives. Our study aimed to evaluate the results of controlling blood pressure and blood homocysteine levels by perindopril in patients with primary hypertension. Materials and Methods. A cross-sectional descriptive study with a longitudinal follow-up was conducted on 105 primary hypertensive patients treated with perindopril. Results. The results of our study showed that after 6 weeks of treatment with perindopril, the proportion of patients with the target blood pressure (BP) level accounted for 70.5%, the rate of grade 1 hypertension decreased from 61.0% to 25.7%, grade 2 blood pressure decreased from 17.1% to 3.8%, and there was no case of grade 3 hypertension. At the same time, we also found that the rate of BP control in the group of patients who controlled Hcy below a threshold of 15 μmol/L was significantly higher than in the other group

p

<

0.05

. Concerning the efficacy of decreasing homocysteine in blood, we discovered that after 6 weeks of treatment with perindopril, the proportion of patients with elevated homocysteine reduced considerably from 74.3% to 40%

p

<

0.05

. In addition, the homocysteine concentration was 4.33 mol/L lower after treatment than before treatment (95% CI: 3.69–4.97)

p

<

0.05

. Conclusion. Perindopril helps control blood pressure and reduces blood homocysteine levels in patients with primary hypertension.
A Comparison of Nursing Activity Score Means for Missed Care Dimensions in Intensive Care Unit Patients
Authors: Mohammadi Fatemeh , Souza Nogueira Lilia de , Hanifi Nasrin , Bahraminejad Nasrin 
Published: October 2023

Background. The workload of nurses in the intensive care unit (ICU) can affect the quality of nursing services. Aim. This study aimed to determine the relationship between the nursing activity score and missed care in patients hospitalized in the ICU in Zanjan, Iran. Methods. This observational and prospective study was conducted from April 3 to September 18 in 2021. The study utilized a patient and nurse profile questionnaire, the Nursing Activity Score (NAS), and a checklist for missed care as research tools. Missed care was observed in the 301 patients for whom the NAS was calculated. Analysis of variance (ANOVA) was used to investigate the differences in mean levels of missed care. Logistic regression models were used to assess the association between factors and missed nursing care. Results. Results show that the medical ICU’s mean NAS was 76.31 (95% CI: −13.06–14.89). In 9 dimensions of care, the extent of missed care was 40.7%. In the care dimensions of assessment, hand hygiene, and infection control, the mean NAS had a statistically significant increase at higher levels of missed care (

P

< 0.5). Furthermore, work experience was identified as a protective factor for missed care (OR = 0.59, 95% CI: 0.37–0.94, χ2 = = 4.97,

p

= 0.026). Conclusion. The study revealed a high incidence of missed care. The study revealed that the mean workload was high in certain dimensions of care such as assessment, hand hygiene, and infection control. The increase in workload for nurses results in lost care. Nonetheless, the utilization of experienced nurses can help mitigate this problem. However, utilizing experienced nurses can help reduce this problem.
Gain-of-Function p53 Mutation Acts as a Genetic Switch for TGFβ Signaling–Induced Epithelial-to-Mesenchymal Transition in Intestinal Tumors
Authors: Wang Dong , Nakayama Mizuho , Hong Chang Pyo , Oshima Hiroko , Oshima Masanobu 
Published: October 2023

Abstract

Signaling by TGFβ family cytokines plays a tumor-suppressive role by inducing cell differentiation, while it promotes malignant progression through epithelial-to-mesenchymal transition (EMT). Identification of the mechanisms regulating the switch from tumor suppression to tumor promotion could identify strategies for cancer prevention and treatment. To identify the key genetic alterations that determine the outcome of TGFβ signaling, we used mouse intestinal tumor-derived organoids carrying multiple driver mutations in various combinations to examine the relationship between genotypes and responses to the TGFβ family cytokine activin A. KrasG12D mutation protected organoid cells from activin A–induced growth suppression by inhibiting p21 and p27 expression. Furthermore, Trp53R270H gain-of-function (GOF) mutation together with loss of wild-type Trp53 by loss of heterozygosity (LOH) promoted activin A–induced partial EMT with formation of multiple protrusions on the organoid surface, which was associated with increased metastatic incidence. Histologic analysis confirmed that tumor cells at the protrusions showed loss of apical–basal polarity and glandular structure. RNA sequencing analysis indicated that expression of Hmga2, encoding a cofactor of the SMAD complex that induces EMT transcription factors, was significantly upregulated in organoids with Trp53 GOF/LOH alterations. Importantly, loss of HMGA2 suppressed expression of Twist1 and blocked activin A–induced partial EMT and metastasis in Trp53 GOF/LOH organoids. These results indicate that TP53 GOF/LOH is a key genetic state that primes for TGFβ family-induced partial EMT and malignant progression of colorectal cancer. Activin signaling may be an effective therapeutic target for colorectal cancer harboring TP53 GOF mutations.

Significance:
KRAS and TP53 mutations shift activin-mediated signaling to overcome growth inhibition and promote partial EMT, identifying a subset of patients with colorectal cancer that could benefit from inhibition of TGFβ signaling.
Characterization of Immunosuppressive Myeloid Cells in Merkel Cell Carcinoma: Correlation with Resistance to PD-1 Pathway Blockade
Authors: Tabachnick-Cherny Shira , Pulliam Thomas , Rodriguez Haroldo J. , Fan Xinyi , Hippe Daniel S. , Jones Daniel C. , Moshiri Ata S. , Smythe Kimberly S. , Kulikauskas Rima M. , Zaba Lisa C. , Paulson Kelly G. , Nghiem Paul 
Published: October 2023

Abstract

Purpose:
Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Although essentially all MCCs are antigenic through viral antigens or high tumor mutation burden, MCC has a response rate of only approximately 50% to PD-(L)1 blockade suggesting barriers to T-cell responses. Prior studies of MCC immunobiology have focused on CD8 T-cell infiltration and their exhaustion status, while the role of innate immunity, particularly myeloid cells, in MCC remains underexplored.

Experimental Design:
We utilized single-cell transcriptomics from 9 patients with MCC and multiplex IHC staining of 54 patients’ preimmunotherapy tumors, to identify myeloid cells and evaluate association with immunotherapy response.

Results:
Single-cell transcriptomics identified tumor-associated macrophages (TAM) as the dominant myeloid component within MCC tumors. These TAMs express an immunosuppressive gene signature characteristic of monocytic myeloid-derived suppressor cells and importantly express several targetable immune checkpoint molecules, including PD-L1 and LILRB receptors, that are not present on tumor cells. Analysis of 54 preimmunotherapy tumor samples showed that a subset of TAMs (CD163+, CD14+, S100A8+) selectively infiltrated tumors that had significant CD8 T cells. Indeed, higher TAM prevalence was associated with resistance to PD-1 blockade. While spatial interactions between TAMs and CD8 T cells were not associated with response, myeloid transcriptomic data showed evidence for cytokine signaling and expression of LILRB receptors, suggesting potential immunosuppressive mechanisms.

Conclusions:
This study further characterizes TAMs in MCC tumors and provides insights into their possible immunosuppressive mechanism. TAMs may reduce the likelihood of treatment response in MCC by counteracting the benefit of CD8 T-cell infiltration.
See related commentary by Silk and Davar, p. 1076
Facilitating Harmonization of Variables in Framingham, MESA, ARIC, and REGARDS Studies Through a Metadata Repository
Authors: Mallya Pratheek , Stevens Laura M. , Zhao Juan , Hong Chuan , Henao Ricardo , Economou-Zavlanos Nicoleta , Wojdyla Daniel M. , Schibler Tony , Manchanda Vihaan , Pencina Michael J. , Hall Jennifer L. 
Published: October 2023

BACKGROUND:
High-quality research in cardiovascular prevention, as in other fields, requires inclusion of a broad range of data sets from different sources. Integrating and harmonizing different data sources are essential to increase generalizability, sample size, and representation of understudied populations—strengthening the evidence for the scientific questions being addressed.

METHODS:
Here, we describe an effort to build an open-access repository and interactive online portal for researchers to access the metadata and code harmonizing data from 4 well-known cohort studies—the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, FHS (Framingham Heart Study), MESA (Multi-Ethnic Study of Atherosclerosis), and ARIC (Atherosclerosis Risk in Communities) study. We introduce a methodology and a framework used for preprocessing and harmonizing variables from multiple studies.

RESULTS:
We provide a real-case study and step-by-step guidance to demonstrate the practical utility of our repository and interactive web page. In addition to our successful development of such an open-access repository and interactive web page, this exercise in harmonizing data from multiple cohort studies has revealed several key themes. These themes include the importance of careful preprocessing and harmonization of variables, the value of creating an open-access repository to facilitate collaboration and reproducibility, and the potential for using harmonized data to address important scientific questions and disparities in cardiovascular disease research.

CONCLUSIONS:
By integrating and harmonizing these large-scale cohort studies, such a repository may improve the statistical power and representation of understudied cohorts, enabling development and validation of risk prediction models, identification and investigation of risk factors, and creating a platform for racial disparities research.

REGISTRATION:

URL:
https://precision.heart.org/duke-ninds
.