bluuebunny/crossref_metadata_2025 huggingface dataset:
Trial of Labor Compared With Elective Cesarean Delivery for Low-Lying Placenta
Authors: Froeliger Alizée , Madar Hugo , Jeanneteau Pauline , Ruiz Vanessa , Le Lous Maela , Perrotin Franck , Winer Norbert , Dreyfus Michel , Merviel Philippe , Mattuizzi Aurélien , Jauniaux Eric , Sentilhes Loïc
Published: August 2022

OBJECTIVE:

To compare outcomes of women with low-lying placenta by planned mode of delivery and distance from the internal os distance.

METHODS:

Six tertiary maternity hospitals in France participated in this retrospective multicenter study of births from 2007–2012. Women with low-lying placenta, defined as an internal os distance of 20 mm or less, who gave birth after 35 weeks of gestation were included and classified in the planned trial-of-labor or elective cesarean delivery groups. The primary endpoint was severe postpartum hemorrhage (PPH) defined as blood loss exceeding 1,000 mL. Secondary outcomes were composite variables of severe maternal and neonatal morbidity. We used multivariable logistic regression and propensity scores to compare outcomes by planned mode of delivery.

RESULTS:

Among 128,233 births during the study period, 171 (0.13%) women had low-lying placenta: 70 (40.9%) in the trial-of-labor group and 101 (59.1%) who underwent elective cesarean delivery. The rate of severe PPH was 22.9% (16/70, 95% CI 13.7–34.4) for the trial-of-labor group and 23.0% (23/101, 95% CI 15.2–32.5) for the cesarean delivery group (P=.9); severe maternal and neonatal morbidity rates were likewise similar (2.9% vs 2.0% [P=.7] and 12.9% vs 9.9% [P=.5], respectively). Trial-of-labor was not significantly associated with a higher rate of severe PPH after multivariable logistic regression and propensity score-weighted analysis (adjusted odds ratio [aOR] 1.42, 95% CI 0.62–3.24 [P=.4]; and aOR 1.34, 95% CI 0.53–3.38 [P=.5], respectively). The vaginal delivery rate in the trial-of-labor group was 50.0% (19/38) in those with an internal os distance of 11–20 mm and 18.5% (5/27) in those with a distance of 1–10 mm.

CONCLUSION:

Our results support a policy of offering a trial of labor to women with low-lying placenta after 35 weeks of gestation and an internal os distance of 11–20 mm. An internal os distance of 1–10 mm reduces the likelihood of vaginal birth considerably, compared with 11–20 mm, but without increasing the incidence of severe PPH or severe maternal morbidity.
Acute Pelvic Pain Due to Spontaneous Hemorrhage of a Gartner Duct Cyst
Authors: Quinto Lauren , Huff Cristina Wallace , Page-Ramsey Sarah M.
Published: August 2022

BACKGROUND:

Gartner duct cysts develop from mesonephric duct remnants. They are usually small and asymptomatic, but complications can arise and are uncommonly reported.

CASE:

A 44-year-old patient presented with acute pelvic pain and pressure, a new vaginal mass, and urinary retention. Examination and magnetic resonance imaging revealed a large, expanding, complex paravaginal mass with extension into the paracervical and ischiorectal spaces, causing cephalad displacement of the uterus. A vaginal approach to cyst incision, hemorrhage control, and marsupialization resulted in complete resolution of symptoms. Pathology demonstrated a Gartner duct cyst without evidence of malignancy.

CONCLUSION:

Spontaneous hemorrhage of a Gartner duct cyst, although rare, may cause acute symptoms and a new vaginal mass. This diagnosis should be considered in the evaluation of acute-onset pelvic pressure and pain.
Association of Progestogens and Venous Thromboembolism Among Women of Reproductive Age
Authors: Cockrum Richard H. , Soo Jackie , Ham Sandra A. , Cohen Kenneth S. , Snow Shari G.
Published: August 2022

OBJECTIVE:

To evaluate associations between use of seven progestogens and incident acute venous thromboembolism (VTE) among women of reproductive age.

METHODS:

This nested matched case–control study identified women aged 15–49 years from January 1, 2010, through October 8, 2018, in the IBM MarketScan databases, a nationwide sample of private insurance claims in the United States. After exclusions, 21,405 women with incident acute VTE (case group), identified by diagnosis codes, were matched 1:5 by year of birth and index date through risk set sampling to 107,025 women without prior VTE (control group). From lowest to highest systemic dose based on a modified hierarchy, progestogens studied were levonorgestrel-releasing intrauterine device (LNG-IUD), oral norethindrone, etonogestrel implant, oral progesterone, oral medroxyprogesterone acetate, oral norethindrone acetate, and depot medroxyprogesterone acetate (DMPA). Conditional logistic regression models adjusted for 16 VTE risk factors were used to estimate odds ratios and 99% CIs for incident acute VTE associated with current progestogen use compared with nonuse. The primary analysis treated each progestogen as a binary exposure. Dose, which varied for oral formulations, and chronicity were explored separately. Significance was set at P<.01 to allow for multiple comparisons.

RESULTS:

Current use of higher-dose progestogens was significantly associated with increased odds of VTE compared with nonuse (oral norethindrone acetate: adjusted odds ratio [aOR] 3.00, 99% CI 1.96–4.59; DMPA: aOR 2.37, 99% CI 1.95–2.88; and oral medroxyprogesterone acetate: aOR 1.98, 99% CI 1.41–2.80). Current use of other progestogens was not significantly different from nonuse (LNG-IUD, etonogestrel implant, and oral progesterone) or had reduced odds of VTE (oral norethindrone). Sensitivity analyses that assessed misclassification bias supported the primary findings.

CONCLUSION:

Among reproductive-aged women using one of seven progestogens, only use of norethindrone acetate and medroxyprogesterone acetate—considered higher-dose progestogens—was significantly associated with increased odds of incident acute VTE. The roles of progestogen type, dose, and indication for use warrant further study.
Implementation of Office Hysteroscopy for the Evaluation and Treatment of Intrauterine Pathology
Authors: Orlando Megan S. , Bradley Linda D.
Published: August 2022

Hysteroscopy provides a minimally invasive strategy to evaluate intrauterine pathology and manage conditions such as abnormal uterine bleeding, infertility, intrauterine adhesions, müllerian anomalies, and intrauterine foreign bodies. Increasing access to hysteroscopy procedures in the office has the potential to improve patient care by minimizing financial and logistical barriers, aiding in streamlined diagnosis and treatment planning, and potentially averting unnecessary operative procedures and anesthesia. Office hysteroscopy refers to procedures performed in outpatient settings where pain management involves no medications, oral nonsedating medications, local anesthetic agents, or oral or inhaled conscious sedation. We present best practices for the implementation of hysteroscopy in an office setting. These include appropriate patient selection, optimal procedural timing, cervical preparation for patients at highest risk of cervical stenosis or pain with dilation, individualized pain-management strategies, use of distension media, and video monitoring to engage patients in the procedure. We describe miniaturized equipment for use in the office setting and “no-touch” vaginoscopic approaches to limit patient discomfort. With appropriate training and experience, office hysteroscopy presents a simple and cost-effective modality for optimizing gynecologic care for our patients.
Rate of Mesh Erosion After Sacrocolpopexy With Concurrent Supracervical Compared With Total Hysterectomy
Authors: Nassif Joseph , Yadav Ghanshyam S. , Orejuela Francisco J. , Turrentine Mark A.
Published: August 2022

OBJECTIVE:

To estimate the effect of concomitant supracervical hysterectomy compared with total hysterectomy during abdominal sacrocolpopexy on the rate of mesh erosion by performing a systematic review and meta-analysis of the existing literature.

DATA SOURCES:

From database inception through January 2022, we explored MEDLINE, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials. Studies comparing the rate of mesh erosion in women undergoing abdominal sacrocolpopexy who had concomitant supracervical hysterectomy compared with total hysterectomy were included.

DATA EXTRACTION AND SYNTHESIS:

Two reviewers separately ascertained studies, obtained data, and gauged study quality. The rate of mesh erosion was compared, and odds ratios (ORs) with 95% CIs were estimated.

TABULATION, INTEGRATION, AND RESULTS:

Nineteen studies with 10,572 women who underwent abdominal sacrocolpopexy were identified, including 4,285 women in the supracervical group and 6,287 women in the total hysterectomy group. The overall mean postprocedure follow-up time was 30.7±15.1 months (median 12.4, range 1.5–44.2). The median (95% CI) point prevalence of mesh erosion was 0.36% (0–1.9%) in women who had supracervical hysterectomy compared with 3.8% (1.8–8.7%) in women who had total hysterectomy. The overall rate of mesh erosion in women who had supracervical hysterectomy was lower compared with women who had total hysterectomy (pooled OR 0.26, 95% CI 0.18–0.38, I2 0%).

CONCLUSION:

In women with symptomatic apical pelvic organ prolapse who undergo abdominal sacrocolpopexy with concomitant hysterectomy, supracervical hysterectomy is associated with a lower risk of mesh erosion compared with total hysterectomy.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42022301862.
Using Longitudinally Linked Data to Measure Severe Maternal Morbidity Beyond the Birth Hospitalization in California
Authors: Carmichael Suzan L. , Girsen Anna I. , Ma Chen , Main Elliot K. , Gibbs Ronald S.
Published: August 2022

Most studies of severe maternal morbidity (SMM) include only cases that occur during birth hospitalizations. We examined the increase in cases when including SMM during antenatal and postpartum (within 42 days of discharge) hospitalizations, using longitudinally linked data from 1,010,250 births in California from September 1, 2016, to December 31, 2018. For total SMM, expanding the definition resulted in 22.8% more cases; for nontransfusion SMM, 45.1% more cases were added. Sepsis accounted for 55.5% of the additional cases. The increase varied for specific indicators, for example, less than 2% for amniotic fluid embolism, 7.0% for transfusion, 112.9% for sepsis, and 155.6% for acute myocardial infarction. These findings reiterate the importance of considering SMM beyond just the birth hospitalization and facilitating access to longitudinally linked data to facilitate a more complete understanding of SMM.
Screening for High-Risk Human Papillomavirus Using Passive, Self-Collected Menstrual Blood
Authors: Naseri Sara , Young Stephen , Cruz Giovanna , Blumenthal Paul D.
Published: August 2022

OBJECTIVE:

To assess concordance and acceptability of a modified menstrual pad compared with a clinician-collected high-risk human papillomavirus (HPV) sample.

METHODS:

This was a prospective observational study. Women presenting for either cervical cancer screening or with a history of high-risk HPV positivity were eligible. Three samples were requested from participants: 1) clinician-collected cervical specimens; 2) self-collected vaginal swabs; and 3) a modified menstrual pad, which was taken home for use during the next menstruation. All samples were processed using the Cobas HPV test. Menstrual pad dried blood spots were eluted, then similarly processed.

RESULTS:

Of 153 women enrolled in the study, 106 provided menstrual pad samples and clinician-collected cervical specimens for high-risk HPV analysis. For samples in which the interval between the clinician-collected specimen and the menstrual pad sample was less than 2 months, the concordance was 94% (95% CI 83–98). For women who tested positive for high-risk HPV who presented for general screening and those with more than cervical intraepithelial neoplasia 2, menstrual pad and clinician-collected specimen agreement was 100% (95% CI 32.5–100). Among participants, 22.9% expressed discomfort with the self-collected vaginal swabs and opted out of collection. Overall, 94.0% of participants preferred the menstrual pad over clinician-collected sampling. Twelve patients were found to be positive for HPV on the menstrual pad sample but negative on the clinician-collected specimen.

CONCLUSION:

Among women who tested positive for HPV, the menstrual pad showed highly concordant results compared with clinician-collected sampling. This collection approach shows promise for integration into cervical cancer prevention programs.
Dethiosulfovibrio faecalis sp. nov., a novel proteolytic, non-sulphur-reducing bacterium isolated from a marine aquaculture solid waste bioreactor
Authors: Grabowski Stephen , Apolinario Ethel A. , Schneider Nicholas O. , Marshall Christopher W. , Sowers Kevin
Published: August 2022

A new

Dethiosulfovibrio

strain, designated F2BT, was isolated from an anaerobic digester for treating solid waste from a marine recirculating aquaculture system. The motile, Gram-negative, non-spore-forming curved rods were 2–7 µm long and 1 µm in diameter. Growth occurred at temperatures ranging from 20 to 40 °C with a maximum rate of growth at 30 °C. The pH range for growth was pH 6.0–8.0, with a maximum rate of growth at pH 7.5. This isolate was halotolerant growing in NaCl concentrations ranging from 0 to 1.6 M with a maximum rate of growth at 0.4 M. Similarly to the five described

Dethiosulfovibrio

species, this obligate anaerobe isolate was fermentative, capable of utilizing peptides, amino acids and some organic acids for growth, but unlike described strains in the genus did not reduce thiosulphate or elemental sulphur to hydrogen sulphide during fermentation of organic substrates. The G+C content of 55 mol% is similar to the described

Dethiosulfovibrio

species. The average nucleotide identity analysis between whole genome sequences showed less than 93.15% sequence similarity between strain F2BT and the five other described

Dethiosulfovibrio

species. Differences in the physiological and phylogenetic characteristics between the new strain and other

Dethiosulfovibrio

specied indicate that F2BT represents a novel species of this genus and the epithet Dethiosulfovibrio faecalis sp. nov. is proposed. The type strain is F2BT (=DSM 112078T=KCTC25378T).
Wide distribution of Escherichia coli carrying IncF plasmids containing bla
NDM-5 and rmtB resistance genes from hospitalized patients in England
Authors: Turton Jane F. , Pike Rachel , Perry Claire , Jenkins Claire , Turton Jack A. , Meunier Danièle , Hopkins Katie L
Published: August 2022

Introduction. The New Delhi metallo-β-lactamase (NDM) variant NDM-5 was first described in 2011 in an isolate of

Escherichia coli

. We noted that a high proportion of isolates of

E. coli

positive for bla
NDM carbapenemase genes submitted to the UK Health Security Agency (formerly Public Health England) between 2019 and mid-2021 carried the bla
NDM-5 allele, with many co-harbouring rmtB, rendering them highly resistant to aminoglycosides as well as to most β-lactams.

Hypothesis/Gap Statement. This observation suggested that a common plasmid may be circulating.

Aim. To compare these isolates and describe the plasmids carrying these resistance elements.

Methodology. All isolates were sequenced on an Illumina platform, with five also subjected to long-read nanopore sequencing to provide complete assemblies. The locations of bla
NDM-5, rmtB and other associated genetic elements were identified. Susceptibility testing to a wide range of antibiotics was carried out on representative isolates.

Results. The 34 isolates co-harbouring bla
NDM-5 and rmtB were from 14 hospital groups and six different regions across England and consisted of 11 distinct sequence types. All carried IncF plasmids. Assembly of the NDM plasmids in five isolates revealed that they carried rmtB and bla
NDM-5 in an IncF conjugative plasmid ranging in size from 85.5 to 161 kb. All carried a highly conserved region, previously described in

E. coli

plasmid pHC105-NDM, that included bla
TEM-1B and rmtB followed by sequence bounded by two IS26 elements containing ΔISAba125, bla
NDM-5, ble, trpF and tat followed by ISCR1 and an integron with sul1, aadA2 and dfrA12 cassettes. This arrangement has been described in isolates from other countries and continents, suggesting that such plasmids are widely distributed, at least in

E. coli

, with similar plasmids also found in

Klebsiella pneumoniae

. Tested isolates were resistant to most antibiotics except colistin, fosfomycin and tigecycline.

Conclusion. These observations suggest that conjugative plasmids carrying a highly conserved resistance gene segment have become widespread in England and elsewhere. This study highlights the value of routine whole-genome sequencing in identifying genetic elements responsible for resistance dissemination.
Ageing impairs the neuro-vascular interface in the heart
Authors: Wagner Julian U. G. , Tombor Lukas , Malacarne Pedro Felipe , Kettenhausen Lisa-Maria , Panthel Josefine , Cipca Maria , Stilz Kathrin A. , Fischer Ariane , Muhly-Reinholz Marion , Abplanalp Wesley T. , John David , Buchmann Giulia K. , Angendohr Stephan , Amin Ehsan , Scherschel Katharina , Klöcker Nikolaj , Kelm Malte , Schüttler Dominik , Clauss Sebastian , Guenther Stefan , Boettger Thomas , Braun Thomas , Bär Christian , Nardini Eleonora , Osmanagic-Myers Selma , Meyer Christian , Zeiher Andreas M. , Brandes Ralf P. , Luxán Guillermo , Dimmeler Stefanie
Published: August 2022

Aging is a major risk factor for impaired cardiovascular health. The aging myocardium is characterized by electrophysiological dysfunctions such as a reduced heart rate variability. These alterations can be intrinsic within cardiomyocytes, but might be modulated by the cardiac autonomic nervous system, as well1. It is known that nerves align with vessels during development2, but the impact of aging on the cardiac neuro-vascular interface is unknown. Here, we report that aging reduces nerve density specifically in the left ventricle and dysregulates vascular-derived neuro-regulatory genes. Aging leads further to a down-regulation of miR-145 and de-repression of the neuro-repulsive factor Semaphorin-3A. miR-145 deletion increased Sema3a expression and reduced axon density, thus mimicking the observed aged heart phenotype. Removal of senescent cells, which accumulated with chronological age while nerve density declined, rescued from age-induced dennervation, reduced Sema3a expression and preserved heart rate variability. These data suggest that senescence-associated regulation of neuro-regulatory genes contributes to a declined nerve density of the aging heart and thereby to a reduced heart rate variability.
How researchers experience the impact of consortia and ERC funding schemes on their science
Authors: Meirmans Stephanie , Paul Herman J.
Published: August 2022

Policy makers push for consortia science geared towards addressing important issues. Such consortia are expected to target societal problems, be international, to engage in trans- or interdisciplinary research, to involve stakeholders and have specific plans for implementation. For example, Horizon Europe focuses on five missions that are being targeted by such type of consortia. This, however, does not seem to be the type of funding that active researchers appreciate the most: a recent letter signed by over 24.000 researchers clearly shows their preference for ERC grants. What are the underlying reasons for this difference? Here, we share insights on how natural science and medical researchers experience the impact of these funding schemes using interviews. Our findings highlight that the two different types of funding schemes have a different performative effect on research, and that ERC-type funding aligns most with how scientists think research should best be conducted.
Antibody Response Following COVID-19 Boosters During the Omicron Wave in the United States: A Decentralized, Digital Health, Real-World Study
Authors: Doornek Tosha , Shao Nan , Burton Paul , Ceddia Francesca , Fraile Belen
Published: August 2022

As the coronavirus disease 2019 (COVID-19) pandemic evolves, new methods that enable real-world studies can provide public health information regarding long-term immunity following vaccination and booster campaigns. We conducted an observational trial to assess antibody levels against SARs-CoV-2 following COVID-19 vaccine boosters in adults in the United States during the omicron wave. This study utilized mobile health technology to recruit and enroll participants in combination with at-home blood collection self-conducted by participants and self-administration of surveys. The results show that when compared with the Pfizer-only primary/booster COVID-19 vaccine, the Moderna-only primary/booster vaccine substantially boosts and maintains high antibody titers over time against the ancestral strain and variants, including BA.1; the geometric mean ratios were generally statistically significantly greater when comparing the Moderna-only to the Pfizer-only vaccine/booster series over much of the study period. These observations suggest that priming/boosting with the Moderna vaccine may be highly protective against COVID-19; such data are vital to inform future recommendations for COVID-19 boosters and to assess the emergence of variants.
Testing, Tracing, and Vaccination Targets for Containment of the US Monkeypox Outbreak: A Modeling Study
Authors: Chitwood Melanie H. , Kwon Jiye , Savinkina Alexandra , Walker Jo , Bilinski Alyssa , Gonsalves Gregg
Published: August 2022

We estimate the levels of community testing, contact tracing, and vaccination required to reduce the effective reproduction number (Rt) of Monkeypox Virus (MPXV) below 1 for high risk men who have sex with men. We found that the critical threshold to vaccinate depends on the basic reproduction number of MPXV and on other public health measures. This analysis provides a framework for quantitative targets toward MPXV containment.
LC-MS/MS-PRM Quantification of IgG glycoforms using stable isotope labeled IgG1 Fc glycopeptide standard
Authors: Sanda Miloslav , Yang Qiang , Zong Guanghui , Chen He , Zheng Zhihao , Dhani Harmeet , Khan Khalid , Kroemer Alexander , Wang Lai-Xi , Goldman Radoslav
Published: August 2022

Targeted quantification of proteins is a standard methodology with broad utility, but targeted quantification of glycoproteins has not reached its full potential. The lack of optimized workflows and isotopically labeled standards limits the acceptance of glycoproteomics quantification. In this paper, we introduce an efficient and streamlined chemoenzymatic synthesis of a library of isotopically labeled glycopeptides of IgG1 which we use for quantification in an energy optimized LC-MS/MS-PRM workflow. Incorporation of the stable isotope labeled N-acetylglucosamine enables an efficient monitoring of all major fragment ions of the glycopeptides generated under the soft collision induced dissociation (CID) conditions which reduces the CVs of the quantification to 0.7-2.8%. Our results document, for the first time, that the workflow using a combination of stable isotope labeled standards with intra-scan normalization enables quantification of the glycopeptides by an electron transfer dissociation (ETD) workflow as well as the CID workflow with the highest sensitivity compared to traditional workflows., This was exemplified by a rapid quantification (13-minute) of IgG1 Fc glycoforms from COVID-19 patients.

Graphic Abstract
Sleep/wake changes in perturbational complexity in rats and mice
Authors: Cavelli Matias Lorenzo , Mao Rong , Findlay Graham , Driessen Kort , Bugnon Tom , Tononi Giulio , Cirelli Chiara
Published: August 2022

In humans, the level of consciousness can be assessed by quantifying the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst (st, state transitions). These measures are consistently high in wake and rapid eye movement (REM) sleep and low in dreamless non-REM (NREM) sleep, deep slow wave anesthesia, and coma. The neuronal mechanisms underlying the reduction of PCI/PCIst in unconscious states remain largely unexplored. The extent to which different cortical areas or layers contribute to these measures is also unknown. To address these questions, here we first validate the use of PCIst in freely moving rats (8 males) and mice (12, 4 females) by showing that its values are lower in NREM sleep and slow wave anesthesia than in wake or REM sleep, as in humans. We then show that low PCIst is associated with the occurrence of an OFF period of neuronal silence. Moreover, the stimulation of deep, but not superficial, cortical layers leads to reliable changes in PCIst across sleep/wake and anesthesia. Finally, consistent changes in PCIst can be measured independent of which single area is being stimulated or recorded, except for recordings in mouse prefrontal cortex. These experiments directly support the hypothesis that PCIst is low when an OFF period disrupts causal interactions in cortical networks. Moreover, they demonstrate that, as in humans, PCIst can be used for the reliable assessment of vigilance states in unresponsive animals, without the need to rely on behavioral outputs such as the righting reflex.

Significance Statement

The level of consciousness can be assessed in humans by measuring the spatiotemporal complexity of cortical responses using the Perturbational Complexity Index (PCI) and related PCIst. These measures discriminate between conscious and unconscious conditions with high sensitivity and specificity and work in unresponsive patients. However, the neuronal mechanisms underlying PCI/ PCIst are largely unexplored. Moreover, since they reflect evoked responses from many cortical regions, it is unclear whether some areas or layers are more informative than others. Here we validate PCIst in rodents, provide direct evidence for the underlying neuronal mechanisms, and show that reliable changes in PCIst can almost always be obtained independent of which single area is stimulated or recorded, but only after stimulation of deep layers.
An efficient opal-suppressor tryptophanyl pair creates new routes for simultaneously incorporating up to three distinct noncanonical amino acids into proteins in mammalian cells
Authors: Osgood Arianna O. , Zheng Yunan , Roy Soumya Jyoti Singha , Loynd Conor , Jewel Delilah , Chatterjee Abhishek
Published: August 2022

The site-specific incorporation of multiple distinct noncanonical amino acids (ncAAs) into proteins in mammalian cells is an emergent technology with much potential. For each different ncAA to be incorporated, this technology requires a distinct orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pair that recognizes a distinct nonsense codon. The aaRS/tRNA pairs currently available for ncAA mutagenesis in eukaryotes are all traditionally used to decode the TAG nonsense codon. Unfortunately, these pairs suppress the other two nonsense codons, TGA or TAA, at a significantly lower level, compromising the scope of multi-ncAA mutagenesis. Here we report that the bacteria-derived tryptophanyl (EcTrp) pair is an excellent TGA-suppressor in mammalian cells. Additionally, we show that this pair does not cross-react with any of the three previously established aaRS/tRNA pairs. Consequently, the TGA-suppressing EcTrp pair can be combined with TAG-suppressing pyrrolysyl (archaeal), tyrosyl (bacterial), or leucyl (bacterial) pairs to develop three new routes for dual-ncAA incorporation in mammalian cells. We show that all three platforms enable site-specific incorporation of two distinct ncAAs into proteins – including a full-length humanized antibody – with excellent fidelity and good efficiency. Finally, we combined the EcTrp pair with the bacterial Tyr pair and the archaeal pyrrolysyl pair to site-specifically incorporate different combinations of three distinct ncAAs into a reporter protein in mammalian cells.
DNA methylation clocks for clawed frogs reveal evolutionary conservation of epigenetic ageing
Authors: Zoller Joseph A. , Parasyraki Eleftheria , Lu Ake T. , Haghani Amin , Niehrs Christof , Horvath Steve
Published: August 2022

DNA methylation-based biomarkers of ageing (epigenetic clocks) have been developed for many mammals, but not yet for amphibian species. We generated DNA methylation data from African clawed frogs (Xenopus laevis) and Western clawed frogs (Xenopus tropicalis), from adult tissues, whole embryos, and tadpoles. We used an array platform designed for CpGs that are highly conserved in mammals to build multiple DNA methylation-based estimators of age for Xenopus. We found that dual species clock could be developed that apply to both humans and frogs (human-clawed frog clocks), and whose high accuracy supports that epigenetic ageing processes are evolutionary conserved outside mammals. Crossing vast evolutionary distances, we characterize age-related CpGs in Xenopus and mammalian species. Highly conserved positively age-related CpGs are located in neural-developmental genes such as uncx, tfap2d as well as nr4a2 implicated in age-associated disease. As in human clocks, positively age-related CpGs are associated with Polycomb repressive complex 2 (PRC2) target sites. Negative age-related CpGs are associated with genes involved in synaptic transmission. We conclude that signatures of epigenetic ageing are evolutionary conserved between frogs and mammals and that the associated genes relate to neural-developmental processes, altogether opening opportunities to employ Xenopus as a model organism to study development and ageing.
Longitudinal analyses after COVID-19 recovery or prolonged infection reveal unique immunological signatures after repeated vaccinations
Authors: Hisamatsu Daisuke , Ikeda Akari , Ito Lisa , Matsushita Yasushi , Hiki Makoto , Mori Hirotake , Tabe Yoko , Naito Toshio , Akazawa Chihiro
Published: August 2022

Background

To strategically develop preventive and therapeutic measures against coronavirus disease 2019 and its causative virus, SARS-CoV-2, it is critical to fully characterize immune response and sustained immune activation following viral infection and vaccination. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights into how we can optimize therapeutic and preventive care, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals.

Methods

We evaluated the expression of 29 cytokines and assessed their correlation with neutralizing potency. We further investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants of concern, and in vaccinated individuals.

Results

Correlation analyses showed that the relationship between neutralizing activity and cytokine expression differed according to disease severity and viral strain. Furthermore, long-term longitudinal analyses revealed that post-vaccination neutralizing potential was more strongly associated with various cytokine expression levels in recovered patients than in naïve individuals. Notably, we found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for one year.

Conclusion

Our results showed that distinct immune responses occur depending on the viral strain suggesting that therapeutic options should be selected on a case-by-case basis. Furthermore, longitudinal analyses revealed biomarker candidates that correlated with repeated vaccination that may be applicable to therapies regulating specific immune responses and novel monoclonal antibodies.

Funding

This work was supported by the Institutional Funds, YOKOYAMA Foundation for Clinical Pharmacology (#YRY-2121), and the Japan Society for the Promotion of Science (JSPS)/ Ministry of Education, Culture, Sports, Science, and Technology (MEXT) KAKENHI; Grant-in-Aid for Early-Career Scientists (#21K15888).
RapidAIM 2.0: a high-throughput assay to study functional response of human gut microbiome to xenobiotics
Authors: Li Leyuan , Mayne Janice , Beltran Adrian , Zhang Xu , Ning Zhibin , Figeys Daniel
Published: August 2022

Our gut microbiome functions like an organ, having its own set of functions and roles which can be modulated by various types of xenobiotic and biotic components. High-throughput screening approaches that are established based onin vitroorex vivocell, tissue or organ models greatly accelerate drug discovery and our understanding of biological and pathological processes within these systems. There was a lack of a high-throughput compatible functional screening approach of the gut microbiome until we recently developed the RapidAIM (Rapid Assay of Individual Microbiome). RapidAIM combines an optimized culturing model, which maintains the taxonomic and functional profiles of the human gut microbiomein vitro, and a high-throughput metaproteomics workflow to gain deep functional insights into microbiome responses. This protocol describes the most recently optimized 2.0 version of RapidAIM, consisting of extensive details on stool sample collection, biobanking,in vitroculturing and stimulation, microbiome sample processing, and metaproteomics measurement and data analysis. To demonstrate the typical outcome of the protocol, we show an example of using RapidAIM 2.0 to evaluate the effect of prebiotic kestose onex vivoindividual human gut microbiomes biobanked with five different workflows; we also show that kestose had consistent functional effects across individuals and can be used as positive control in the assay.
Rapid generation of precision preclinical cancer models using regulatable in vivo base editing
Authors: Katti Alyna , Foronda Miguel , Zimmerman Jill , Zafra Maria Paz , Goswami Sukanya , Gardner Eric E. , Diaz Bianca J. , Simon Janelle M , Wuest Alexandra , Luan Wei , Fernandez Maria Teresa Calvo , Kadina Anastasia P. , Walker John A , Holden Kevin , Sánchez Rivera Francisco J. , Lowe Scott W. , Dow Lukas E.
Published: August 2022

Single nucleotide variants (SNVs) comprise the majority of cancer-associated genetic changes and can have diverse effects on protein function. Despite a comprehensive catalogue of SNVs across human cancers, little is known about their impact on tumor initiation and progression. To enable the functional interrogation of cancer-associated SNVs, we developed a murine system for temporal and regulatable in vivo cytosine base editing (iBE). The iBE mice show robust, doxycycline-dependent expression across a broad range of tissues with no evidence of DNA or RNA off-target effects. Transient iBE induction drives efficient creation of individual or multiple SNVs in intestinal, lung, and pancreatic organoids, while temporal iBE regulation allows controlled sequential genome editing. Moreover, in situ delivery of plasmid-based or synthetic sgRNAs to target tissues facilitates the simple and rapid generation of pre-clinical cancer models. Overall, iBE is a powerful in vivo platform to define and interrogate the genetic drivers of cancer.
Simulation of the mechanical behavior of self-healing composite materials
Authors: Madia Evgenia , Tserpes Konstantinos , Polydoropoulou Panagiota , Pantelakis Spyros
Published: August 2022

Purpose

The purpose of this study is the investigation of self-healing materials containing encapsulated healing agents embedded in a polymer matrix with dispersed catalysts. In recent years, the high performance and design flexibility of composite materials have led to their widespread use in the aeronautics, space, automotive and marine fields. Simultaneously, as the need for advanced material properties has increased, many studies have been conducted on multifunctional materials, focusing on different fields of their desired capabilities.

Design/methodology/approach

A multiscale model was developed to simulate the effect of microcapsules on the mechanical behavior of the polymer matrix. Furthermore, the effects of microcapsule diameter and microcapsule concentration on the mechanical behavior of the composite were studied. Digimat and Ansys software were used to simulate the self-healing composites.

Findings

There is a trade-off between the efficiency of the microcapsules and the degradation of the properties of the composite material.

Originality/value

The generated model simulated an encapsulated healing agent in a polymeric matrix.
The undigital behavior of innovative startups: empirical evidence and taxonomy of digital innovation strategies
Authors: Centobelli Piera , Cerchione Roberto , Esposito Emilio , Passaro Renato , Quinto Ivana
Published: August 2022

Purpose

This paper aims to conceptualize the digital behavior of startups and investigate the emerging behaviors about digital strategies of the Italian startup firms enrolled in the Startup Act policy initiative. Digital technologies were divided into intra- and inter-organizational digital infrastructures, and this categorization offers startups the opportunity to identify a set of enabling technologies that could be used to improve their digital strategies.

Design/methodology/approach

An empirical analysis has been conducted to investigate the degree of adoption of digital intra- and inter-organizational digital infrastructures in the entire population of 6,178 Italian firms listed in the Register of Innovative Startups.

Findings

The paper proposes a taxonomy bringing together four startup behaviors for adopting digital technologies: digital follower, technical influencer, social influencer and digital leader. From the perspective of policy makers, considering the financial efforts that public authorities are supporting in the last decade, implications are mainly concerned with policy measures aimed both to reinforce the overall adoption of digital technologies and to develop a balanced adoption of intra- and inter-organizational digital infrastructures.

Originality/value

Measures addressed to support female and foreign entrepreneurship could be useful to support a more dynamic and well-balanced cultural and racial contamination, thus improving the adoption of digital tools.
How do Islamic banks manage earnings? Application of various measurement models in the Iranian Islamic banking system
Authors: Ghaemi Asl Mahdi , Ghasemi Doudkanlou Mohammad
Published: August 2022

Purpose

This study aims to identify and compare the measurement models of earnings management (EM) appropriate to the Iranian Islamic banking system. The importance of reported profit figures has motivated business executives, who also perform financial reporting, to manipulate these figures. These measures are referred to as “earnings management,” which negatively influence the quality of reported earnings and financial statements' reliability.

Design/methodology/approach

In this study, four methods, namely, Jones (1991), modified Jones (Dechow et al., 1995), Kasznik (1999) and Kothari et al. (2005), were used to measure the EM index in 25 Iranian Islamic banks (IBs) registered with the Tehran Stock Exchange and/or the Central Bank of Iran. The study covered the period 2005–2020. Following the aforementioned methods, this research implemented templates that were repeatedly tested in subsequent studies using accruals to discover EM.

Findings

The results show that the Kasznik (1999) model is the preferred and compatible model with the Iranian Islamic banking system's accrual behaviour due to the consistency of the measurement coefficients with theoretical and previous research findings. Therefore, total accruals, including discretionary accruals and non-discretionary accruals, have the most correspondence with (1) property, machinery and equipment; (2) the change in cash flow from operating activities; and (3) the difference of change in revenue (ΔREV) and change in net receivable accounts (ΔREC).

Originality/value

This is the first investigation in the Iranian Islamic banking system. The research contributes to the Iranian Islamic banking system literature on the implements of EM, which could be appealed to in the context of developing countries like Iran. Finally, this study highlights the different EM capabilities in Islamic banking systems similar to the Iranian banking arrangement.
The impact of supply chain social capital on supply chain performance: a longitudinal analysis
Authors: Ye Yuxiao , Yang Lu , Huo Baofeng , Zhao Xiande
Published: August 2022

Purpose

Drawing on the resource-based view (RBV), this study aims to investigate the impact of social capital, namely, structural (information sharing), cognitive (shared value) and relational (relationship commitment) capital in the supplier and the customer side on supply chain performance in a longitudinal design. It further aims to examine the moderating effect of change in competition intensity.

Design/methodology/approach

Based on two-wave data collected from 203 manufacturers in China, this study uses the ordinary least square and first-difference regression methods to test the proposed relationships.

Findings

The results show the effect of social capital on supply chain performance and the dynamic nature of supply chain social capital. The causal analysis further reveals the significance of supplier-side structural and relational capital in improving supply chain performance. Moreover, competitive intensity plays an important moderating role.

Originality/value

This study, to the best of the authors’ knowledge, is one of the first to demonstrate the longitudinal effect of supply chain social capital on supply chain performance.
Integrated optimization of design and production for personalized products
Authors: Cheng Bayi , Shi Xinyan , Gao Junwei , Zhu Huijun
Published: August 2022

Purpose

The purpose of this paper is to study the profit optimization of manufacturers who provide personalized products to customers, thus avoiding additional operational costs and response times in the production process of personalized product design.

Design/methodology/approach

First, the authors present an integrated model for optimizing profit where the design and production of personalized products are both considered. The authors propose the concept of personalization level and four cases of personalization level are considered including top, high, medium and low levels. Polynomial-time optimal rules are provided for each level by analyzing 17 subcases where all possible personalized products are considered. Then, the authors compare the obtained profit of personalized products with the optimal profit of standardized products.

Findings

At low and high levels of personalization, personalized manufacturing is more profitable for specific products with specific characteristics. At the top and middle level of individuation, assuming that the product has certain characteristics, whether the best choice to produce personalized products depends on the level of individuation chosen by customers.

Originality/value

An important decision issue for manufacturers is whether to produce personalized or standardized products. In this study, the authors consider this decision problem and analyze the operational functions of personalized products. The authors hope to provide theoretical support in the operational management of manufacturers offering personalized products.
Decision-making biases in women entrepreneurs: the novices vs the habitual
Authors: Nouri Pouria
Published: August 2022

Purpose

Decision-making biases play substantial roles in entrepreneurs' decisions and the fate of entrepreneurial enterprises, as well. Previous studies have assumed all entrepreneurs are homogeneous in their proneness to biases, therefore inadvertently creating a crucial research gap by ignoring the role of business experience in the genesis of biases. Furthermore, there is a lack of research on women entrepreneurs' decision-making biases. Thus, this paper's main objective is to explore two influential biases of overconfidence and over-optimism in novice and habitual women entrepreneurs.

Design/methodology/approach

The data for this study were collected by conducting semi-structured interviews with 21 Iranian novice and habitual women entrepreneurs active in four high-tech sectors of biotech, nanotech, aerospace and advanced medicine. The gathered data were analyzed by thematic analysis.

Findings

According to the findings, while habitual entrepreneurs are prone to all three types of overconfidence (overestimation, overplacement and overprecision) and over-optimism, novice entrepreneurs do not show any signs of overplacement or overprecision.

Practical implications

There are certain valuable implications resulting from this study that could be of use for not only future researchers in the field of entrepreneurial decision-making and women entrepreneurship but also for women entrepreneurs running entrepreneurial enterprises, especially small businesses.

Originality/value

This paper offers certain novel contributions to the field of entrepreneurship by not only exploring biases in women entrepreneurs exclusively but also scrutinizing biases in novice (first-time) and habitual (experienced) entrepreneurs comparatively.
Conceptualizing industrial workplace learning: an information systems perspective
Authors: Shahlaei Charlotte A. , Lundh Snis Ulrika
Published: August 2022

Purpose

The purpose of this paper is to identify the constituent parts of learning in the manufacturing work context and understand why these parts are key in the learning of the employees.

Design/methodology/approach

The data was collected from two sources: a literature review of the Information Systems literature to establish an initial picture of what learning in relation to digital technologies entails and in-depth interviews with engineers in the automotive industry whose knowledge-intensive work is exposed to substantial digital transformation.

Findings

The authors first identified three constituent parts for learning: change, reflection and deliberation. When the authors cross-checked the initial findings through in-depth interviews with the engineers, it was found that these three themes trigger learning through three different mechanisms, that is, balancing newness, finding point of reference and organizing actively. Thus, the findings of this paper extend beyond a categorical identification of what constitutes learning to also illustrate why learning entails these constituent parts.

Research limitations/implications

This paper implies that progressive learning requires active organizing of learning stages. The data is limited to the review of the Information Systems field. The authors have also only focused on the automotive industry as the representative sector in the manufacturing industry.

Practical implications

Applying the model of progressive learning can be a primary way to actively plan and organize learning opportunities for employees. This is key for supporting learning culture in organizations that are exposed to continuous and disruptive changes.

Social implications

A significant part of social sustainability is based on sustainable employability and feelings of contentment at work. This paper is an attempt to highlight how sustainable employability can be achieved by providing effective learning opportunities at work.

Originality/value

The originality of this paper emerges from two sources. First, the authors conducted the literature review and in-depth interviews by devising innovative methods because of the challenges of identifying when (informal) learning has occurred at work. Second, the authors owe the in-depth interviews to the first author’s extensive familiarity with the automotive industry and the knowledge and rapport acquired through her prior longitudinal research on the engineers’ work. It was this background that allowed the authors to find out when these engineers were about to leave the firm because of discontent about their competence development.