bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate sensing and cellular metabolism: role in fine tuning antiviral immune responses
Authors: Ahmed Duale , Al-Daraawi Malak , Cassol Edana
Published: January 2023

Several studies over the last decade have identified intimate links between cellular metabolism and macrophage function. Metabolism has been shown to both drive and regulate macrophage function by producing bioenergetic and biosynthetic precursors as well as metabolites (and other bioactive molecules) that regulate gene expression and signal transduction. Many studies have focused on lipopolysaccharide-induced reprogramming, assuming that it is representative of most inflammatory responses. However, emerging evidence suggests that diverse pathogen-associated molecular patterns (PAMPs) are associated with unique metabolic profiles, which may drive pathogen specific immune responses. Further, these metabolic pathways and processes may act as a rheostat to regulate the magnitude of an inflammatory response based on the biochemical features of the local microenvironment. In this review, we will discuss recent work examining the relationship between cellular metabolism and macrophage responses to viral PAMPs and describe how these processes differ from lipopolysaccharide-associated responses. We will also discuss how an improved understanding of the specificity of these processes may offer new insights to fine-tune macrophage function during viral infections or when using viral PAMPs as therapeutics.
ITGB4 deficiency in airway epithelia enhances HDM-induced airway inflammation through hyperactivation of TLR4 signaling pathway
Authors: Zhou Kai , Yuan Lin , Liu Huijun , Du Xizi , Yao Ye , Qin Ling , Yang Ming , Xu Kun , Wu Xinyu , Wang Leyuan , Xiang Yang , Qu Xiangping , Qin Xiaoqun , Liu Chi
Published: January 2023

Airway epithelial cells (AECs) are the first cell barrier of the respiratory system against external stimuli that play a critical role in the development of asthma. It is known that AECs play a key role in asthma susceptibility and severity. ITGB4 is a downregulated adhesion molecule in the airway epithelia of asthma patients, which was involved in the exaggerated lung inflammation after allergy stimulation. Toll-like receptor 4 (TLR4) in AECs has also been shown to play a crucial role in the development of lung inflammation in asthma patients. However, the specific intrinsic regulatory mechanism of TLR4 in AECs are still obscure. In this article, we demonstrated that ITGB4 deficiency in AECs enhances HDM-induced airway inflammation through hyperactivation of the TLR4 signaling pathway, which is mediated by inhibition of FYN phosphorylation. Moreover, TLR4-antagonist treatment or blockade of FYN can inhibit or exaggerate lung inflammation in HDM-stressed ITGB4-deficient mice, separately. Together, these results demonstrated that ITGB4 deficiency in AECs enhances HDM-induced lung inflammatory response through the ITGB4-FYN-TLR4 axis, which may provide new therapeutic approaches for the management of lung inflammation in asthma.
Changing Epidemiology of COVID-19 in Children and Adolescents Over Four Successive Epidemic Waves in South Africa, 2020–2022
Authors: Chiwandire Nicola , Jassat Waasila , Groome Michelle , Kufa Tendesayi , Walaza Sibongile , Wolter Nicole , von Gottberg Anne , Zar Heather J , Reubenson Gary , Tempia Stefano , Ebonwu Joy , Govender Nevashan , Ntshoe Genevie , Shonhiwa Andronica Moipone , Blumberg Lucille , Cohen Cheryl
Published: January 2023

Background

South Africa experienced four waves of SARS-CoV-2 infection, dominated by Wuhan-Hu, Beta, Delta, and Omicron (BA.1/BA.2). We describe the trends in SARS-CoV-2 testing, cases, admissions, and deaths among children and adolescents in South Africa over successive waves.

Methods

We analyzed national SARS-CoV-2 testing, case, and admissions data from March 2020 to February 2022 and estimated cumulative rates by age group for each endpoint. The severity in the third versus the fourth wave was assessed using multivariable logistic regression.

Results

Individuals ≤18 years comprised 35% (21,008,060/60,142,978) of the population but only 12% (424,394/3,593,644) of cases and 6% (26,176/451,753) of admissions. Among individuals ≤18 years, infants had the highest admission (505/100,000) rates. Testing, case, and admission rates generally increased successively in the second (Beta) and third (Delta) waves among all age groups. In the fourth (Omicron BA.1/BA.2) wave, the case rate dropped among individuals ≥1 year but increased among those <1 year. Weekly admission rates for children <1 year (169/100,000) exceeded rates in adults (124/100,000) in the fourth wave. The odds of severe COVID-19 in all admitted cases were lower in the fourth wave versus the third wave in each age group, but they were twice as high in admitted cases with at least one comorbidity than those without.

Conclusions

The admission rate for children <5 years was higher in the fourth wave than in previous waves, but the overall outcomes were less severe. However, children with at least one comorbidity had increased odds of severe disease, warranting consideration of prioritizing this group for vaccination.
New perforated radiation shield for anesthesiologists: Monte Carlo simulation of effects
Authors: Yanagawa Ayaka , Takata Takeshi , Onimaru Taichi , Honjo Takahiro , Sajima Takeyuki , Kakinuma Akihito , Kataoka Akihisa , Kotoku Jun’ichi
Published: January 2023

Catheterization for structural heart disease (SHD) requires fluoroscopic guidance, which exposes health care professionals to radiation exposure risk. Nevertheless, existing freestanding radiation shields for anesthesiologists are typically simple, uncomfortable rectangles. Therefore, we devised a new perforated radiation shield that allows anesthesiologists and echocardiographers to access a patient through its apertures during SHD catheterization. No report of the relevant literature has described the degree to which the anesthesiologist’s radiation dose can be reduced by installing radiation shields. For estimating whole-body doses to anesthesiologists and air dose distributions in the operating room, we used a Monte Carlo system for a rapid dose-estimation system used with interventional radiology. The simulations were performed under four conditions: no radiation shield, large apertures, small apertures and without apertures. With small apertures, the doses to the lens, waist and neck surfaces were found to be comparable to those of a protective plate without an aperture, indicating that our new radiation shield copes with radiation protection and work efficiency. To simulate the air-absorbed dose distribution, results indicated that a fan-shaped area of the dose rate decrease was generated in the area behind the shield, as seen from the tube sphere. For the aperture, radiation was found to wrap around the backside of the shield, even at a height that did not match the aperture height. The data presented herein are expected to be of interest to all anesthesiologists who might be involved in SHD catheterization. The data are also expected to enhance their understanding of radiation exposure protection.
Challenging the ‘Youth Gaze’: Building Diversity into Refugee and Asylum Reception and Integration Programmes
Authors: Oliver Caroline , Geuijen Karin , Dekker Rianne
Published: January 2023

Reception and integration programmes have often a dominant socio-economic focus that supports refugees’ swift movement into the labour market. This article examines the assumptions that such programmes make about their core target group and how this corresponds with participants’ diverse needs, drawing on conceptual work around the intersectionalities of age, relationalities, and migrant capital to do so. It employs data from interviews with, and observations of residents of an asylum seeker centre in Utrecht, the Netherlands, participating in an innovative programme that aimed to help them ‘integrate from day one’ through co-education and co-housing. We examine the assumptions of the programme, including its inclusive orientation, but show how it appealed implicitly to younger participants. By exploring experiences of participation for a more marginal group of participants in the mid and later phases of professional lives, we show how the programme worked better for a core, younger group, but in doing so, inevitably supported those already advantaged. We argue that programmes need to be adaptive and responsive to the heterogeneity of participants, who vary by age, relationalities and possession of resources among other intersectionalities, to support all the populations they serve.
Discovering gravitationally lensed gravitational waves: predicted rates, candidate selection, and localization with the Vera Rubin Observatory
Authors: Smith Graham P , Robertson Andrew , Mahler Guillaume , Nicholl Matt , Ryczanowski Dan , Bianconi Matteo , Sharon Keren , Massey Richard , Richard Johan , Jauzac Mathilde
Published: January 2023

Secure confirmation that a gravitational wave (GW) has been gravitationally lensed would bring together these two pillars of General Relativity for the first time. This breakthrough is challenging for many reasons, including: GW sky localization uncertainties dwarf the angular scale of gravitational lensing, the mass and structure of gravitational lenses is diverse, the mass function of stellar remnant compact objects is not yet well constrained, and GW detectors do not operate continuously. We introduce a new approach that is agnostic to the mass and structure of the lenses, compare the efficiency of different methods for lensed GW discovery, and explore detection of lensed kilonova counterparts as a direct method for localizing candidates. Our main conclusions are: (1) lensed neutron star mergers (NS–NS) are magnified into the ‘mass gap’ between NS and black holes, therefore selecting candidates from public GW alerts with high mass gap probability is efficient, (2) the rate of detectable lensed NS–NS will approach one per year in the mid-2020s, (3) the arrival time difference between lensed NS–NS images is $1\, \rm s\lesssim \Delta \mathit{ t}\lesssim 1\, yr$, and thus well-matched to the operations of GW detectors and optical telescopes, (4) lensed kilonova counterparts are faint at peak (e.g. rAB ≃ 24–26 in the mid-2020s), fade quickly ($d\lt 2\, \rm d$), and are detectable with target of opportunity observations with large wide-field telescopes. For example, just ≲ 0.25 per cent of Vera C. Rubin Observatory’s observing time will be sufficient to follow up one well-localized candidate per year. Our predictions also provide a physically well-defined basis for exploring electromagnetically the exciting new ‘mass gap’ discovery space.
Probing the multiwavelength emission scenario of GRB 190114C
Authors: Klinger Marc , Tak Donggeun , Taylor Andrew M , Zhu Sylvia J
Published: January 2023

Multiwavelength observation of the gamma-ray burst, GRB 190114C, opens a new window for studying the emission mechanism of GRB afterglows. Its very high energy (VHE; ≳ 100 GeV) detection has motivated an inverse Compton interpretation for the emission, but this has not been tested. Here, we revisit the early afterglow emission from 68 to 180 s and perform the modelling likelihood analysis with the keV to TeV data sets. We compute for the first time the statistical preference in the combined synchrotron (syn) and synchrotron self-Compton (SSC) model over the syn-only model. In agreement with earlier analyses, between 68 and 110 s an unstable preference for the SSC model can be found, which can also be explained by systematic cross-calibration effect between the included instruments. We conclude that there is no stable statistical preference for one of the two models.
Spectroscopic follow-up of statistically selected extremely metal-poor star candidates from GALAH DR3
Authors: Da Costa G S , Bessell M S , Nordlander Thomas , Hughes Arvind C N , Buder Sven , Mackey A D , Spitler Lee R , Zucker D B
Published: January 2023

The advent of large-scale stellar spectroscopic surveys naturally leads to the implementation of machine learning techniques to isolate, for example, small sub-samples of potentially interesting stars from the full data set. A recent example is the application of the t-SNE statistical method to ∼600 000 stellar spectra from the GALAH survey in order to identify a sample of candidate extremely metal-poor (EMP; [Fe/H] ≤ –3) stars. We report the outcome of low-resolution spectroscopic follow-up of 83 GALAH EMP candidates that lack any previous metallicity estimates. Overall, the statistical selection is found to be efficient (∼one-third of the candidates have [Fe/H] ≤ –2.75) with low contamination (<10 per cent have [Fe/H] > –2), and with a metallicity distribution function that is consistent with previous work. Five stars are found to have [Fe/H] ≤ –3.0, one of which is a main sequence turnoff star. Two other stars are revealed as likely carbon-enhanced metal-poor (CEMP) stars of type CEMP-s, and a known carbon star is re-identified. The results indicate that the statistical selection approach employed was successful, and therefore it can be applied to forthcoming even larger stellar spectroscopic surveys with the expectation of similar positive outcomes.
Quantitative determination of minimum spanning tree structures: using the pulsar tree for analysing the appearance of new classes of pulsars
Authors: García C R , Torres Diego F
Published: January 2023

In this work, we introduce a quantitative methodology to define what is the main trunk and what are the significant branches of a minimum spanning tree (MST). We apply it to the pulsar tree, i.e. the MST of the pulsar population constructed upon a Euclidean distance over the pulsar’s intrinsic properties. Our method makes use of the betweenness centrality estimator, as well as of non-parametric tests to establish the distinct character of the defined branches. Armed with these concepts, we study how the pulsar population has evolved throughout history and analyse how to judge whether a new class of pulsars appears in new data, future surveys, or new incarnations of pulsar catalogs.
Probing large-scale ionizing background fluctuation with Lyman α forest and galaxy cross-correlation at z = 2.4
Authors: Long Heyang , Hirata Christopher M
Published: January 2023

The amplitude of the metagalactic ultraviolet background (UVB) at large scales is impacted by two factors. First, it naturally attenuates at scales larger than mean-free path of UVB photons due to the absorption by neutral intergalactic medium. Second, there are discrete and rare ionizing sources distributing in the Universe, emitting the UVB photons, and thus enhancing the local UVB amplitude. Therefore, for cosmological probe that is sensitive to the UVB amplitude and capable of detecting the large scale like Lyman α forest spectrum, the fluctuation due to the clustering of ionizing sources becomes a significant factor for Lyman α flux transmission and leave imprints on Lyman α flux power spectrum at these large scales. In this work, we make use of a radiative transfer model that parametrizes the UVB source distribution by its bias bj and shot noise $\overline{n}_{\rm j}$. We estimate the constraints on this model through the cross-correlation between Lyman α forest survey and galaxy survey, using the DESI Lyman α forest survey and the Roman Space Telescope emission line galaxy survey as an example. We show the detection sensitivity improvement for UVB parameters from disjoint to maximal overlap of DESI + Roman survey strategy. We also show that the degeneracy of two ionizing source parameters can be broken by increasing the overlapping survey area. Our results motivate survey strategies more dedicated to probe the UVB large-scale fluctuations.
The impact of the COVID-19 pandemic and stringent social distancing measures on health-related quality of life and COVID-19 infection rates in patients with rheumatic disease: a longitudinal analysis through the pandemic
Authors: Cox Natasha , Raizada Sabrina R , Barkham Nick , Venkatachalam Srinivasan , Sheeran Tom P , Adizie Tochukwu , Sapkota Hem , Scott Ian C , Muller Sara , Bateman James
Published: January 2023

Objective

The aim was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and stringent social isolation measures on patients with rheumatic disease (RD) from the beginning of the pandemic (April 2020).

Methods

In this UK-based single-centre, prospective, observational cohort study, all RD follow-up patients at our centre were invited by SMS text message in April 2020 to participate in the study. Participants completed questionnaires at four time points between April 2020 and December 2021. We collected demographics, clinically extremely vulnerable (CEV) status, short form 12 mental (MCS) and physical health component scores (PCS) for health-related quality of life, vaccination status, COVID-19 infection rates and incidence of long COVID.

Results

We enrolled 1605 patients (female, 69.0%; CEV, 46.5%); 906 of 1605 (56.4%) completed linked responses to our final questionnaire. MCS improved (+0.6, P < 0.05), whereas PCS scores deteriorated (−1.4, P < 0.001) between April 2020 and December 2021. CEV patients had worse mental and physical health scores than non-CEV patients at entry (PCS, 36.7 and 39.3, respectively, P < 0.001; MCS, 40.9 and 43.0, respectively, P < 0.001) and at each time point throughout the study; both mental and physical health outcomes were worse in CEV compared with non-CEV patients (P < 0.001 and P = 0.004, respectively). At study close, 148 of 906 (16.3%) reported COVID infection, with no difference in infection, vaccination or long COVID rates between CEV and non-CEV patients.

Conclusions

Mental and physical health in RD patients has changed throughout the pandemic; outcomes for both metrics of health were worse in CEV patients, although there were no differences in infection rates between the groups. These data might assist the understanding and planning of future health-care policy and social restrictions in RD patients.

Trial registration

ClinicalTrials.gov, www.clinicaltrials.gov, NCT04542031.
Factor Momentum
Authors: Arnott Robert D , Kalesnik Vitali , Linnainmaa Juhani T
Published: January 2023

Factors display strong cross-sectional momentum that subsumes momentum in industries and other portfolio characteristics. The profits of all these momentum strategies—based on factors, industries, and other characteristics—significantly correlate with each other and therefore likely emanate from the same source. If factors display momentum, so will any set of portfolios with cross-sectional variation in factor loadings. Consistent with factors being at the root of momentum, we find that momentum in industry-neutral factors explains industry momentum, but industry momentum explains none of the factor momentum. Cross-sectional factor momentum concentrates in the first few highest-eigenvalue factors and is distinct from time-series factor momentum.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Rheumatoid factor recognizes specific domains of the IgG heavy chain complexed with HLA class II molecules
Authors: Zhang Shanshan , Tsuji Hideaki , Jin Hui , Kitagori Koji , Akizuki Shuji , Nakashima Ran , Yoshifuji Hajime , Tanaka Masao , Arase Hisashi , Ohmura Koichiro , Morinobu Akio
Published: January 2023

Objective

We previously reported that RF recognized the IgG heavy chain (IgGH)/RA-susceptible HLA class II molecule complex. In the present study, we investigated the molecular mechanisms underlying HLA binding to and the RF recognition of IgGH.

Methods

We synthesized various types of IgGH segments, including VH, CH1, CH2 and CH3, and transfected them with or without HLA class II molecules into the Human Embryonic Kidney 293T cell line. IgGH single domains linked with the HLA-Cw3 peptide, which binds to the binding groove of the HLA class II molecule, were also synthesized. The expression of IgGH domains on the cell surface and their recognition by RF were examined using flow cytometry.

Results

Flag-tagged IgGH segments containing CH1 (CH1, VH-CH1, CH1-CH2, VH-CH1-CH2, CH1-CH2-CH3 and VH-CH1-CH2-CH3) were clearly presented on the cell surface by HLA-DR4, while segments without the CH1 domain were expressed at a low level, and the CH3 single domain was only weakly detected on the cell surface, even with HLA-DR4. We then transfected IgGH single domains linked to the Cw3 peptide together with HLA-DR4 and showed that RF-containing sera from RA patients only recognized the CH3 domain and none of the other single domains. When various segments without the Cw3 peptide were transfected with HLA-DR4, only the CH1-CH2-CH3 segment and full-length IgGH were detected by the sera of RA patients.

Conclusion

The CH1 domain of IgGH binds to the RA-susceptible HLA-DR molecule and is expressed on the cell surface. RF specifically recognizes the CH3 domain of the IgGH/HLA-DR4 complex.
Does Labetalol Trigger False Positive Drug Testing Results?
Authors: Bithi Nazmin , Merrigan Stephen D. , McMillin Gwendolyn A.
Published: January 2023

Objectives

Labetalol, an α- and β-adrenergic antagonist used to treat hypertension in pregnancy has been blamed for causing false-positive amphetamine and methamphetamine results. In this study, we tested 3 concentrations of labetalol prepared with 4 specimen types (urine, plasma, meconium, and umbilical cord tissue), for amphetamine, methamphetamine, and several other drugs with screen and confirmation tests.

Methods

Residual drug-free specimens were pooled. Labetalol hydrochloride dissolved in methanol was used to prepare spikes in triplicate per specimen type (2.7, 50, and 100 μM), which were tested with 41 previously validated drug tests performed by immunoassay or liquid chromatography tandem mass spectrometry (LC-MS/MS).

Results

Labetalol triggered false-positive amphetamine and methamphetamine results by immunoassay in meconium but did not trigger positive results for any of the targeted drugs or drug metabolites tested by LC-MS/MS. No positive results were generated by any immunoassay or LC-MS/MS test included in the study, when challenged with high concentrations of labetalol in urine, plasma, or umbilical cord tissue.

Conclusions

In summary, false-positive results can be generated by labetalol when tested by immunoassay, but false-positive results are not expected when testing is performed by highly specific analytical approaches such as LC-MS/MS.
HIV and obesity: updates in management strategies
Authors: Parra-Rodriguez Luis , O’Halloran Jane A.
Published: January 2023

Purpose of review

Weight gain has emerged as an important problem in people with HIV (PWH). When dealing with obesity, PWH face additional challenges to those without HIV. Understanding the nature of the problem and the modern evidence is essential to optimize management and identify knowledge gaps.

Recent findings

Some PWH treated with antiretroviral therapy (ART) gain unhealthy amounts of weight and develop consequences of obesity. Newer agents have been consistently associated with excessive weight gain. Key studies are underway to inform the optimal use of specific ART in PWH dealing with obesity. For weight management, behavioral interventions fostering a healthier and active lifestyle, coupled with pharmacological therapies such as glucagon-like peptide 1 receptor agonists may be effective strategies in PWH, as recently demonstrated in those without HIV, although data in this regard is pending.

A growing body of research has come to light in recent years regarding weight gain and obesity in PWH. However, much of the knowledge that inform current practices is extrapolated from studies in people without HIV. Modern ART regimens may promote excessive weight gain in some, and more research is needed to optimize ART selection and the use of weight loss medications.
The Illusion of Health Privacy in Obstetrics-gynecology
Authors: Rothstein Mark A.
Published: January 2023

Many health professionals and patients erroneously believe that professional ethics and laws protect the privacy of sensitive records in obstetrics-gynecology. The Health Insurance Portability and Accountability Act Privacy Rule permits disclosure of health records without authorization for public health, law enforcement, and other reasons. Individuals also may be compelled to authorize the release of their records in applying for employment, life insurance, or government benefits. Disclosure of sensitive health information has increased because of comprehensive electronic health records, patient-developed data from mobile devices, consolidation of medical practices, and law enforcement interest in reproductive health records attributable to the change in abortion laws.
CAP and LSM as determined by VCTE are independent predictors of all-cause mortality in the US adult population
Authors: Vilar-Gomez Eduardo , Vuppalanchi Raj , Gawrieh Samer , Samala Niharika , Chalasani Naga
Published: January 2023

Background and Aim:

Data retrospective cohort studies have shown that liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) can predict mortality in patients with NAFLD, however, its ability to predict mortality at a population level is unknown. We investigated the ability of LSM and controlled-attenuation parameter (CAP) by TE to predict mortality in a prospective US cohort.

Approach and Results:

A total of 4192 US adults aged ≥18 years enrolled in the National Health, and Nutrition Examination Survey (NHANES) (2017–2018) with reliable information on CAP and LSM by TE were included in this analysis. All-specific and cause-specific mortality were ascertained by linkage to National Death Index records through December 31, 2019. Cox models were used to estimate HR and 95% CI. During a mean follow-up of 24.4 months, there were 68 deaths (1.6%). CAP (adjusted HR: 1.01, 95% CI: 1.0–1.05), and LSM (adjusted HR: 1.06, 95% CI: 1.02–1.11) were independently associated with overall mortality. NAFLD by CAP ≥285 had a 2.2-fold (95% CI: 1.0–4.7) increased odds of mortality compared with non-NAFLD. Cumulative mortality rates were significantly higher in participants with LSM of 9.7–13.5 (advanced fibrosis) and LSM ≥13.6 (cirrhosis) as compared with LSM <9.7; p value for trend across groups <0.01. LSM ≥13.6 displayed the highest mortality risk (adjusted HR: 3.2, 95% CI: 1.3–7.8). Compared with LSM <10 [absence of advanced chronic liver disease (ACLD)], LSM 10–19.9 (likely ACLD), and ≥20 kPa (likely ACLD with clinically significant portal hypertension) conferred a 3.4-fold (95% CI: 1.0–13.8) and 5.2-fold (95% CI: 1.2–22.3) increase in hazards of mortality.

Conclusions:

Our study findings highlight the importance of liver health as a predictor of overall mortality at a population level.
Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy
Authors: Hellen Dominick J. , Bennett Ashley , Malla Sudarshan , Klindt Caroline , Rao Anuradha , Dawson Paul A. , Karpen Saul J.
Published: January 2023

Background and Aims:

A recent multicenter genetic exploration of the biliary atresia splenic malformation syndrome identified mutations in the ciliary gene PKD1L1 as candidate etiologic contributors. We hypothesized that deletion of Pkd1l1 in developing hepatoblasts would lead to cholangiopathy in mice.

Approach and Results:

CRISPR-based genome editing inserted loxP sites flanking exon 8 of the murine Pkd1l1 gene. Pkd1l1

Fl/Fl
cross-bred with alpha-fetoprotein-Cre expressing mice to generate a liver-specific intrahepatic Pkd1l1-deficient model (LKO). From embryonic day 18 through week 30, control (Fl/Fl) and LKO mice were evaluated with standard serum chemistries and liver histology. At select ages, tissues were analyzed using RNA sequencing, immunofluorescence, and electron microscopy with a focus on biliary structures, peribiliary inflammation, and fibrosis. Bile duct ligation for 5 days of Fl/Fl and LKO mice was followed by standard serum and liver analytics. Histological analyses from perinatal ages revealed delayed biliary maturation and reduced primary cilia, with progressive cholangiocyte proliferation, peribiliary fibroinflammation, and arterial hypertrophy evident in 7- to 16-week-old LKO versus Fl/Fl livers. Following bile duct ligation, cholangiocyte proliferation, peribiliary fibroinflammation, and necrosis were increased in LKO compared with Fl/Fl livers.

Conclusions:

Bile duct ligation of the Pkd1l1-deficient mouse model mirrors several aspects of the intrahepatic pathophysiology of biliary atresia in humans including bile duct dysmorphogenesis, peribiliary fibroinflammation, hepatic arteriopathy, and ciliopathy. This first genetically linked model of biliary atresia, the Pkd1l1 LKO mouse, may allow researchers a means to develop a deeper understanding of the pathophysiology of this serious and perplexing disorder, including the opportunity to identify rational therapeutic targets.
Improving Outcomes for Bronchiolitis Patients After Implementing a High-Flow Nasal Cannula Holiday and Standardizing Discharge Criteria in a PICU
Authors: Maue Danielle K. , Ealy Aimee , Hobson Michael J. , Peterson Rachel J. , Pike Francis , Nitu Mara E. , Tori Alvaro J. , Abu-Sultaneh Samer
Published: January 2023

OBJECTIVES:

To decrease length of high-flow nasal cannula (HFNC), PICU, and hospital length of stay (LOS).

DESIGN:

Quality improvement project.

SETTING:

A quaternary academic PICU.

PATIENTS:

Patients with bronchiolitis less than 24 months old.

INTERVENTIONS:

After initial implementation of a respiratory therapist (RT)-driven HFNC protocol (Plan-Do-Study-Act [PDSA] 1) in October 2017, additional interventions included adjusting HFNC wean rate (PDSA 2) in July 2020, a HFNC holiday (PDSA 3), and standardized discharge criteria (PDSA 4) in October 2021.

MEASUREMENTS AND MAIN RESULTS:

Duration of HFNC was used as the primary outcome measure. PICU LOS and hospital LOS were used as secondary outcome measures. Noninvasive ventilation use, invasive mechanical ventilation use, and 7-day PICU and hospital readmission rates were used as balancing measures. A total of 1,310 patients were included in this study. Patients in PDSA 2, PDSA 3 and 4 groups were older compared with pre-intervention and PDSA 1 (median of 9 and 10 mo compared with 8 mo; p = 0.01). HFNC duration decreased from 2.5 to 1.8 days after PDSA 1, then to 1.3 days after PDSA 2. PICU LOS decreased from 2.6 to 2.1 days after PDSA 1, 1.8 days after PDSA 2, and 1.5 days after PDSA 3 and 4. Hospital LOS decreased from 5.7 to 4.5 days after PDSA 1, 3.1 days after PDSA 2, and 2.7 days after PDSA 3 and 4. The use of noninvasive ventilation and invasive mechanical ventilation decreased throughout the study from 23.2% in the pre-intervention group, to 6.9% at the end of the project. The 7-day PICU and hospital readmission rates did not increase after implementation. The percentage of patients discharged from the PICU increased from 6.2% to 21.5%.

CONCLUSIONS:

Modifications to an existing RT-driven HFNC protocol and standardization of discharge criteria led to an improvement in outcomes for patients admitted to the PICU with bronchiolitis without an increase in adverse events.
Growth increases but regeneration declines in response to warming and drying at Arctic treeline in white spruce (Picea glauca)
Authors: Jensen Johanna , Boelman Natalie , Eitel Jan , Vierling Lee , Maguire Andrew , Oelkers Rose , Silva Carlos , Andreu-Hayles Laia , D’Arrigo Rosanne , Griffin Kevin L.
Published: January 2023

1.

As a temperature-delineated boundary, the Arctic treeline is predicted to shift northward in response to warming. However, the evidence for northward movement is mixed, with some sections of the treeline advancing while others remain stationary or even retreat. To identify the drivers of this variation, we need a landscape-level understanding of the interactions occurring between climate, tree growth, and population regeneration. In this study, we assessed regeneration alongside annual tree growth and climate during the 20th century. We used an ageheight model combined with tree height from aerial lidar to predict the age structure of 38,652 white spruce trees across 250 ha of Arctic treeline in the central Brooks Range, Alaska, USA. We then used age structure analysis to interpret the trends in regeneration and tree-ring analysis to interpret changes in annual tree growth. The climate became significantly warmer and drier circa 1975, coinciding with divergent responses of regeneration and tree growth. After 1975, regeneration of saplings (trees ≤ 2m tall) decreased compared to previous decades whereas annual growth in mature trees (trees >2m tall) increased by 54% (p<0.0001, Wilcoxon test). Tree-ring width was positively correlated with May-August temperature (p<0.01, Pearson coefficient) during the 20th century. However, after circa 1950, the positive correlation between temperature and growth weakened (i.e., temperature divergence) while the positive correlation with July precipitation strengthened (p<0.01, Pearson coefficient), suggesting that continued drying may limit future growth at this section of Arctic treeline. We conclude that while warmer temperatures appear to benefit annual growth in mature trees, the warmer and drier environmental conditions in spring and summer inhibit regeneration and therefore may be inhibiting the northward advance at this Arctic treeline site. Researchers should consider the interactions between temperature, water availability, and tree age when examining the future of treeline and boreal forest in a changing climate.
A new gene finding tool GeneMark-ETP significantly improves the accuracy of automatic annotation of large eukaryotic genomes
Authors: Bruna Tomas , Lomsadze Alexandre , Borodovsky Mark
Published: January 2023

Large-scale genomic initiatives, such as the Earth BioGenome Project, require efficient methods for eukaryotic genome annotation. Here we present an automatic gene finder, GeneMark-ETP, integrating genomic-, transcriptomic- and protein-derived evidence that has been developed with a focus on large plant and animal genomes. GeneMark-ETP first identifies genomic loci where extrinsic data is sufficient for making gene predictions with ‘high confidence’. The genes situated in the genomic space between the high confidence genes are predicted in the next stage. The set of high confidence genes serves as an initial training set for the statistical model. Further on, the model parameters are iteratively updated in the rounds of gene prediction and parameter re-estimation. Upon reaching convergence, GeneMark-ETP makes the final predictions and delivers the whole complement of predicted genes. GeneMark-ETP outperformed gene finders using a single type of extrinsic evidence. Comparisons with gene finders utilizing both transcript- and protein-derived extrinsic evidence, MAKER2, and TSEBRA, demonstrated that GeneMark-ETP delivered state-of-the-art gene prediction accuracy with the margin of outperforming existing approaches increasing in its applications to larger and more complex eukaryotic genomes.
An analysis of the positive effect of real earnings management on financial performance
Authors: Lim Hyoung Joo , Mali Dafydd
Published: January 2023

Purpose

REM models infer abnormal levels of cashflow from operations (AbCFO), selling, general and admin (AbSGA) and production expenses (AbProd) are opportunistic, based on the supposition that engaging in real activities to meet current earnings targets (t) will negatively influence future performance (t+1). However, from a firm productivity perspective, cost reduction (via AbCFO, AbProd and AbSGA) is interpreted as an efficiency enhancing business strategy. This study therefore differentiates between (1) firms with ineffective management that have engaged in AbCFO, AbProd and AbSGA to achieve an optimal resource-cost mix to generate sales (REMF) and (2) firms with effective management that have not (OEF).

Design/methodology/approach

Using a sample of Korean listed firms over the 2000–2016 sample period, the study utilizes data envelopment analysis to capture the capability of management to generate sales from resources that are directly under their control. The study then compares the incremental effect that managerial decision making can have on real earnings management (REM) and future firm performance (period t+1 to t+5).

Findings

The study makes two important contributions. First, consistent with the efficiency/productivity literature, but contrary to seminal REM studies, empirical results shows that AbCFO, AbProd and AbSGA improve firm performance in period t and t+1 (to t+5), demonstrating “REM” is not opportunistic by default. Second, OEF have higher financial performance compared to REMF, in periods t and t+1.

Originality/value

The study therefore invokes resource-based theory and data envelopment analysis to integrate managerial effectiveness (human capital) into REM modelling. The study therefore extends the basic REM residual model.
The influence of complexity, chance and change on the career crafting strategies of SIEs
Authors: Suarez-Bilbao Blanca , Andresen Maike , Crowley-Henry Marian , O'Connor Edward P.
Published: January 2023

Purpose

Externalities influence the career trajectories of self-initiated expatriates (SIEs) and their respective career crafting. This study aims to explore the international career crafting of SIEs (encompassing their proactive career reflection and construction), taking the combined external influences of complexity, chance and change into consideration.

Design/methodology/approach

The authors employ a qualitative (interpretative) approach, combining career crafting and the chaos theory of careers (CTC) to further understand, from an individual standpoint, the impact of externalities on the career crafting strategies of 24 SIEs who have relocated within the European Union.

Findings

The authors show that SIEs' proactively craft their careers to varying degrees and with varying frequency. The CTC – incorporating complexity, chance and change – allows for a more nuanced understanding of SIEs' career crafting.

Originality/value

This paper applies the concept of career crafting to an international context, exploring the impact of externalities on SIEs' careers. In this way, the authors combine two previously separate theories, extend the application of career crafting to an international career context and emphasise the role of temporality and the whole-life view of career in SIEs’ career crafting approach.
When are trans women treated worse than trans men?
Authors: Rudin Joel , Billing Tejinder , Farro Andrea , Yang Yang
Published: January 2023

Purpose

This paper aims to test penis panic theory, which predicts that trans women will face more discrimination than trans men in some but not all situations.

Design/methodology/approach

Respondents were 262 American college students who were all enrolled in the same undergraduate course. They were presented with a case about coworker resistance to transgender employees' use of the workplace restrooms of their choice. Four versions of a case were randomly distributed as follows: trans woman, restroom with one toilet; trans woman, restroom with three toilets; trans man, restroom with one toilet and trans man, restroom with three toilets.

Findings

The authors observed greater discrimination against trans women compared to trans men when there was one toilet but not when there were three toilets. This supports penis panic theory.

Research limitations/implications

The chief limitation was the use of American college students as respondents. The results may not generalize to practicing managers especially in other countries. Future researchers should develop a scale to measure situational discrimination against trans women. This study should be replicated in other contexts to deepen the understanding of discrimination against trans men and trans women with disabilities, as well as discrimination against nonbinary individuals who identify as neither trans men nor trans women.

Practical implications

Employers need to search for situations in which trans women face greater discrimination than trans men, because they can be resolved in ways that protect the rights of transgender employees no matter how transphobic their coworkers may be. Also, employers need a nuanced approach to combat discrimination that recognizes the unique perspectives of trans men, trans women and other members of the transgender community.

Originality/value

This is the first quantitative study of penis panic theory, and it illuminates the understanding of discrimination against transgender individuals.
Front- and back-end employee satisfaction during service transition
Authors: Karatzas Antonios , Papadopoulos Georgios , Stamolampros Panagiotis , Raja Jawwad Z. , Korfiatis Nikolaos
Published: January 2023

Purpose

Scholars studying servitization argue that manufacturers moving into services need to develop new job roles or modify existing ones, which must be enacted by employees with the right mentality, skill sets, attitudes and capabilities. However, there is a paucity of empirical research on how such changes affect employee-level outcomes.

Design/methodology/approach

The authors theorize that job enrichment and role stress act as countervailing forces during the manufacturer's service transition, with implications for employee satisfaction. The authors test the hypotheses using a sample of 21,869 employees from 201 American manufacturers that declared revenues from services over a 10-year period.

Findings

The authors find an inverted U-shaped relationship between the firm's level of service infusion and individual employee satisfaction, which is flatter for front-end staff. This relationship differs in shape and/or magnitude between firms, highlighting the role of unobserved firm-level idiosyncratic factors.

Practical implications

Servitized manufacturers, especially those in the later stage of their transition (i.e. when services start to account for more than 50% of annual revenues), should try to ameliorate their employees' role-induced stress to counter a drop in satisfaction.

Originality/value

This is one of the first studies to examine systematically the relationship between servitization and individual employee satisfaction. It shows that back-end employees in manufacturing firms are considerably affected by an increasing emphasis on services, while past literature has almost exclusively been concerned with front-end staff.
Economic–statistical design of Bayesian X‾ control chart based on the predictive distribution
Authors: Seirani Razieh , Torabian Mohsen , Behzadi Mohammad Hassan , Seif Asghar
Published: January 2023

Purpose

The purpose of this paper is to present an economic–statistical design (ESD) for the Bayesian X‾ control chart based on predictive distribution with two types of informative and noninformative prior distributions.

Design/methodology/approach

The design used in this study is based on determining the control chart of the predictive distribution and then its ESD. The new proposed cost model is presented by considering the conjugate and Jeffrey's prior distribution in calculating the expected total cycle time and expected cost per cycle, and finally, the optimal design parameters and related costs are compared with the fixed ratio sampling (FRS) mode.

Findings

Numerical results show decreases in costs in this Bayesian approach with both Jeffrey's and conjugate prior distribution compared to the FRS mode. This result shows that the Bayesian approach which is based on predictive density works better than the classical approach. Also, for the Bayesian approach, however, there is no significant difference between the results of using Jeffrey's and conjugate prior distributions. Using sensitivity analysis, the effect of cost parameters and shock model parameters and deviation from the mean on the optimal values of design parameters and related costs have been investigated and discussed.

Practical implications

This research adds to the body of knowledge related to quality control of process monitoring systems. This paper may be of particular interest to quality system practitioners for whom the effect of the prior distribution of parameters on the quality characteristic distribution is important.

Originality/value

economic statistical design (ESD) of Bayesian control charts based on predictive distribution is presented for the first time.
Case study reflections of an internet child abuse material offender informing the development of a proposed assessment instrument
Authors: Garrington Catherine , Kelty Sally , Rickwood Debra , Boer Douglas Pieter
Published: January 2023

Purpose

Internet child abuse material (I/CAM) offences negatively affect children in our own communities and in the wider virtual world. This study aims to understand the differentiation between online (internet) and offline (contact) offenders. The development of the Estimated Risk for Internet Child Sexual Offending (ERICSO), a proposed instrument for I/CAM offenders, incorporated a case study component to test on a known offender before the tool is applied to a wider sample.

Design/methodology/approach

The case study approach provides a unique opportunity for researchers to consider reflections from an I/CAM offender. These insights provide unique perspectives on areas for further exploration, including suggestions for consideration in the assessment and treatment of I/CAM offenders.

Findings

Mr A is a male convicted of possessing I/CAM with previous convictions for contact child sexual offending. During the development of the ERICSO, Mr A provided commentary on proposed questions based on his experiences as an offender and his communications with other offenders. Mr A’s feedback was generally consistent with current research findings, with notable suggestions in recognising the importance of differentiating between fantasy/reality, violence/voyeurism and the role technology plays in I/CAM offences. These reflections will be considered in conjunction with ongoing development and validity studies of the ERICSO to contribute to the targeted assessment and risk-relevant treatment for I/CAM offenders.

Originality/value

The use of a case study in the development of a proposed assessment instrument provides a unique perspective to improve ecological validity.