bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of white-coat hypertension and white-coat uncontrolled hypertension using machine learning algorithm
Authors: Shih Ling-Chieh , Wang Yu-Ching , Hung Ming-Hui , Cheng Han , Shiao Yu-Chieh , Tseng Yu-Hsuan , Huang Chin-Chou , Lin Shing-Jong , Chen Jaw-Wen
Published: November 2022

Aims

The detection of white-coat hypertension/white-coat uncontrolled hypertension (WCH/WUCH) with out-of-office blood pressure (BP) monitoring is time- and resource-consuming. We aim to develop a machine learning (ML)-derived prediction model based on the characteristics of patients from a single outpatient visit.

Methods and results

Data from two cohorts in Taiwan were used. Cohort one (970 patients) was used for development and internal validation, and cohort two (464 patients) was used for external validation. WCH/WUCH was defined as an office BP of ≥140/90 mmHg and daytime ambulatory BP of <135/85 mmHg in treatment-naïve or treated individuals. Logistic regression, random forest (RF), eXtreme Gradient Boosting, and artificial neural network models were trained using 26 patient parameters. We used SHapley Additive exPlanations values to provide explanations for the risk factors. All models achieved great area under the receiver operating characteristic curve (AUROC), specificity, and negative predictive value in both validations (AUROC = 0.754–0.891; specificity = 0.682–0.910; negative predictive value = 0.831–0.968). The RF model was the best performing (AUROC = 0.884; sensitivity = 0.619; specificity = 0.887; negative predictive value = 0.872; accuracy = 0.819). The five most influential features of the RF model were office diastolic BP, office systolic BP, current smoker, estimated glomerular filtration rate, and fasting glucose level.

Conclusion

Our prediction models achieved good performance, underlining the feasibility of applying ML models to outpatient populations for the diagnosis of WCH and WUCH. Further validation with other prospective data sets should be considered in the future.
Strategic reprogramming of implantable cardiac monitors reduces the false-positive remote alert burden in a nurse-led service
Authors: Maines Massimiliano , Degiampietro Massimo , Tomasi Giancarlo , Poian Luisa , Cont Natascia , Peruzza Francesco , Moggio Paolo , Triglione Francesco , Giacopelli Daniele , Del Greco Maurizio
Published: November 2022

Aims

Implantable cardiac monitors (ICMs) can generate false-positive (FP) alerts. Although these devices have an extended programmability, there are no recommendations on their optimization to reduce not-relevant activations.

We tested a strategic programming optimization guide based on the type of FP and investigated the safety and feasibility of the nurse-led insertion of ICMs with a long-sensing vector.

Methods and results

Consecutive patients implanted by trained nurses with long-sensing vector ICM were enrolled in a 1-month observational stage (Phase A). Patients who had ≥10 FP episodes underwent ICM reprogramming based on the predefined guide and were followed for an additional month (Phase B). A total of 78 patients had successful ICM insertion by nurses with a mean R wave amplitude of 0.96 ± 0.43 mV and an 86% P wave visibility. Only one patient reported a significant device-related issue, and nurse-delivered ICM was generally well accepted by the patients. During Phase A, 11 patients (14%) generated most of FP (3,627/3,849; 94%) and underwent ICM reprogramming. In the following month (Phase B), five patients (45%) were free from FP and six (55%) transmitted 57 FP alerts (98% reduction compared with Phase A). The median number of FP per patient was significantly reduced after reprogramming [195 (interquartile range, 50–311) vs. one (0–10), P = 0.0002].

Conclusion

A strategic reprogramming of ICM in those patients with a high FP alert burden reduces the volume of erroneous activations with potential benefits for the remote monitoring service. No concerns were raised regarding nurse-led insertion of ICMs with a long-sensing vector.
Immunomodulators: still having a role?
Authors: Venner Jeffery M , Bernstein Charles N
Published: November 2022

Immunomodulators, particularly the thiopurines and to a lesser extent methotrexate, were standard of care for inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, for >40 years. While there has been a renaissance in available therapies with the advent of biologics and small molecules, an impetus remains for the ongoing use of thiopurines and methotrexate. This is particularly true for the maintenance of remission and when used in combination therapy with infliximab to suppress anti-biologic antibodies. This article summarizes the data behind immunomodulator use in Crohn’s disease, focusing on the beneficial role these drugs still have while acknowledging their clinical limitations.
Origins and Evolution of Human Tandem Duplicated Exon Substitution Events
Authors: Martinez-Gomez Laura , Cerdán-Vélez Daniel , Abascal Federico , Tress Michael L
Published: November 2022

The mutually exclusive splicing of tandem duplicated exons produces protein isoforms that are identical save for a homologous region that allows for the fine tuning of protein function. Tandem duplicated exon substitution events are rare, yet highly important alternative splicing events. Most events are ancient, their isoforms are highly expressed, and they have significantly more pathogenic mutations than other splice events.

Here, we analyzed the physicochemical properties and functional roles of the homologous polypeptide regions produced by the 236 tandem duplicated exon substitutions annotated in the human gene set. We find that the most important structural and functional residues in these homologous regions are maintained, and that most changes are conservative rather than drastic. Three quarters of the isoforms produced from tandem duplicated exon substitution events are tissue-specific, particularly in nervous and cardiac tissues, and tandem duplicated exon substitution events are enriched in functional terms related to structures in the brain and skeletal muscle.

We find considerable evidence for the convergent evolution of tandem duplicated exon substitution events in vertebrates, arthropods, and nematodes. Twelve human gene families have orthologues with tandem duplicated exon substitution events in both Drosophila melanogaster and Caenorhabditis elegans. Six of these gene families are ion transporters, suggesting that tandem exon duplication in genes that control the flow of ions into the cell has an adaptive benefit. The ancient origins, the strong indications of tissue-specific functions, and the evidence of convergent evolution suggest that these events may have played important roles in the evolution of animal tissues and organs.
A family-based approach examining perceptions of an Australian TRYathlon series on children’s health and development
Authors: Caperchione Cristina M , English Madeleine , Sharp Paul , Stolp Sean , Wallace Lee , Harris David , Ashton John
Published: November 2022

Regular physical activity supports children’s physical and psychological health and wellbeing, and provides opportunities to build social and emotional skills such as resilience, confidence, and self-efficacy. Research has demonstrated that mass participant sporting events can serve as important social and environmental correlates of physical activity. This study sought to explore parents and children’s perceived motivations and perspectives of participation in the Australian Sanitarium Weet-Bix Kids TRYathlon (a non-competitive triathlon series), on children’s health and well-being. An exploratory qualitative design utilizing seven focus groups were conducted with 27 family units including 31 parents and 61 children (age 7–15 years old). Data were recorded, professionally transcribed and then analyzed using thematic analysis. Three overarching themes were identified, including (1) motivations for event and physical activity participation, revealing social interaction, peer support and friendly competition as motivators for participation as well as parents’ interest in supporting the development of healthy habits; (2) Perceived physical activity, fitness, and developmental benefits, detailing changes to the types of physical activity children performed as well as opportunities for children to develop physical skills and competencies; and (3) Perceived psychosocial benefits of participation, highlighting opportunities for children to develop and demonstrate independence and autonomy through event participation. Notably, parents and children identified benefits beyond immediate participation including increased family engagement and social support. Mass participant events hold the potential to elicit a range of benefits for children and their families; however, further efforts may be needed to engage less active or disengaged families.
Log Calabi–Yau Structure of Projective Threefolds Admitting Polarized Endomorphisms
Authors: Meng Sheng
Published: November 2022

Let $X$ be a normal projective variety admitting a polarized endomorphism $f$, that is, $f^*H\sim qH$ for some ample divisor $H$ and integer $q>1$. It was conjectured by Broustet and Gongyo that $X$ is of Calabi–Yau type, that is, $(X,\Delta )$ is lc for some effective ${\mathbb {Q}}$-divisor such that $K_X+\Delta \sim _{{\mathbb {Q}}} 0$. In this paper, we establish a general guideline based on the equivariant minimal model program and the canonical bundle formula. In this way, we prove the conjecture when $X$ is a smooth projective threefold.
Using a patient portal as a recruitment tool to diversify the pool of participants in COVID-19 vaccine clinical trials
Authors: Yuh Tiffany , Srivastava Tuhina , Fiore Danielle , Schmidt Harald , Frank Ian , Metzger David , Momplaisir Florence
Published: November 2022

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected racial/ethnic minorities in the United States, who are underrepresented in clinical trials. We assessed the feasibility of using the University of Pennsylvania Health System electronic health record patient portal to diversify the pool of participants in COVID-19 vaccine clinical trials. The patient portal was used to send invitations to eligible individuals living in zip codes with high rates of racial/ethnic minorities. The 5614 invited consisted of 96.7% black, 1.3% Hispanic/Latinx, and 1.5% white. The overall response rate was 5.4%, with lower response rates among Black (3.8%) and Hispanic/Latinx (9.6%) as compared to white individuals (91.6%). Among respondents, black individuals had lower rates of interest in participating (26.7%), as compared to white (65.8%) and Hispanic/Latinx (71.4%) individuals. Of 115 respondents who expressed interest, 9 enrolled in the clinical trial, which included 6 black, 3 white, and 1 Hispanic/Latinx. During phone outreach to nonresponders and decliners, common reasons for declining included mistrust of the COVID-19 vaccine, underlying health conditions, and logistical barriers to trial participation. Because of low rates of patient portal account activation and use, compounded with vaccine hesitancy, this method yielded a small number of interested individuals.
BRASSINOSTEROID-SIGNALING KINASE1-1, a positive regulator of brassinosteroid signalling, modulates plant architecture and grain size in rice
Authors: Tian Peng , Liu Jiafan , Yan Baohui , Zhou Chunlei , Wang Haiyang , Shen Rongxin
Published: November 2022

Brassinosteroids (BRs) are a crucial class of plant hormones that regulate plant growth and development, thus affecting many important agronomic traits in crops. However, there are still significant gaps in our understanding of the BR signalling pathway in rice. In this study, we provide multiple lines of evidence to indicate that BR-SIGNALING KINASE1-1 (OsBSK1-1) likely represents a missing component in the BR signalling pathway in rice. We showed that knockout mutants of OsBSK1-1 are less sensitive to BR and exhibit a pleiotropic phenotype, including lower plant height, less tiller number and shortened grain length, whereas transgenic plants overexpressing a gain-of-function dominant mutant form of OsBSK1-1 (OsBSK1-1A295V) are hypersensitive to BR, and exhibit some enhanced BR-responsive phenotypes. We found that OsBSK1-1 physically interacts with the BR receptor BRASSINOSTEROID INSENSITIVE1 (OsBRI1), and GLYCOGEN SYNTHASE KINASE2 (OsGSK2), a downstream component crucial for BR signalling. Moreover, we showed that OsBSK1-1 can be phosphorylated by OsBRI1 and can inhibit OsGSK2-mediated phosphorylation of BRASSINOSTEROID RESISTANT1 (OsBZR1). We further demonstrated that OsBSK1-1 genetically acts downstream of OsBRI1, but upstream of OsGSK2. Together, our results suggest that OsBSK1-1 may serve as a scaffold protein directly bridging OsBRI1 and OsGSK2 to positively regulate BR signalling, thus affecting plant architecture and grain size in rice.
Why do immigrants become less happy? Explanations for the decrease in life satisfaction of immigrants in Germany over time
Authors: Yaman Firat , Cubi-Molla Patricia , Plagnol Anke C
Published: November 2022

We investigate the life satisfaction (LS) trajectories of immigrants in Germany. Using data from the German Socio-Economic Panel from 1984 to 2015, we find that recently arrived immigrants are more satisfied with their lives than comparable German natives. However, their LS decreases more over time than that of their German counterparts; that is, we observe a negative years-since-migration (YSM)–LS association. We propose and test five possible explanations for this observation: (1) differential effects of declining health between natives and immigrants, (2) the stability of the YSM–LS association over time and across samples, (3) the effects of non-random sample attrition, (4) immigrants’ integration in German society, and (5) differences in the YSM effect across ethnic backgrounds. We find that the decrease in LS among immigrants over time is mostly explained by a combination of deteriorating health and an increase in the importance of health for LS. The extent to which immigrants’ LS changes over time in the host country partly depends on their country of origin. The results suggest that there is scope for policies targeted towards immigrants’ better utilisation of the healthcare system and their integration in host societies to improve immigrants’ LS.
Exposure to itraconazole influences the susceptibility to antifungals, physiology, and virulence of Trichophyton interdigitale
Authors: Carmo Paulo H F , Costa Marliete C , Leocádio Victor A T , Gouveia-Eufrásio Ludmila , Emídio Elúzia C P , Pimentel Samantha P , Paixão Tatiane A , Peres Nalu T A , Santos Daniel A
Published: November 2022

Dermatophytosis is the most common human skin infection worldwide caused by dermatophytes, such as Trichophyton interdigitale and Trichophyton rubrum. Itraconazole (ITZ) is one of the main antifungals used to treat these infections. However, especially for onychomycosis, the treatment requires long-term regimens, increasing the possibility of drug resistance. We evaluated the effects of ITZ in the physiology, virulence, and interaction of T. interdigitale with phagocytes and mice cutaneous infection. In a screening test, fungal growth in the presence of ITZ led to the spontaneous selection of less susceptible T. interdigitale and T. rubrum strains. Interestingly, this phenotype was permanent for some T. interdigitale strains. Then, we studied three T. interdigitale strains: one susceptible and two ITZ-adapted. The ITZ-adapted strains were also less susceptible to the cell wall and membrane stressors, suggesting a multidrug resistance (MDR) phenotype associated with the increased ERG11 and MDR3 expression. These strains also presented substantial alterations in ergosterol content, lipid peroxidation, biofilm, and extracellular matrix production. During interaction with macrophages, ITZ-adapted strains were less engulfed but increased the intracellular oxidative and nitrosative bursts. In addition, ITZ-adapted strains presented a reduced ability to grow in a murine model of dermatophytosis, although causing the same tissue damage as the parental strain. In conclusion, the T. interdigitale ITZ adaptation increases tolerance to antifungals and alters the interaction with macrophages and a mammalian host. We hypothesized that successive exposure to ITZ may influence the emergence of adapted strains and lead to the recalcitrance of dermatophytosis.
Population study of astrophysical false positive detections in the southern plato field
Authors: Bray J C , Kolb U , Rowden P , Farmer Robert , Börner A , Kozhura O
Published: November 2022

For the upcoming PLAnetary Transits and Oscillation of stars (PLATO) satellite mission, a large number of target stars are required to yield a statistically significant number of planet transits. Locating the centres of the long duration observational phase (LOP) fields closer to the Galactic plane will increase the target star numbers but also the astrophysical false positives (FPs) from blended eclipsing binary systems. We utilize the Binary Stellar Evolution and Population Synthesis code, to create a complete synthetic stellar and planetary population for the proposed southern LOP field (LOPS0), as well as for a representative portion of the northern LOP field (LOPN-sub). For LOPS0, we find an overall low FP rate for planets smaller than Neptunes. The FP rate generally shows little variation with Galactic longitude (l), and a modest increase with decreasing Galactic latitude (|b|). The location of the LOPS field centre within the current allowed region is not strongly constrained by FPs. Analysis of LOPN-sub suggests a markedly increased number of FPs across the full range of planet radii at low |b| resulting in approximately twice the percentage of FP detection rate in the LOPN-sub compared to the corresponding southern field segment in the planet radius range −0.2 < log (R/R⊕) ≤ 0.4. However, only a few per cent of fully eclipsing FPs in LOPS0 in this radius range have periods between 180 and 1000 d so the vast majority of FPs are expected to be outside the period range of interest for PLATO.
A Systematic Review of COVID-19 Vaccine Antibody Responses in People With HIV
Authors: Chun Helen M , Milligan Kyle , Agyemang Elfriede , Ford Nathan , Rangaraj Ajay , Desai Shalini , Wilder-Smith Annelies , Vitoria Marco , Zulu Isaac
Published: November 2022

HIV infection is a significant independent risk factor for severe coronavirus disease 2019 (COVID-19) disease and death. We summarize COVID-19 vaccine responses in people with HIV (PWH). A systematic literature review of studies from January 1, 2020, to March 31, 2022, of COVID-19 vaccine immunogenicity in PWH from multiple databases was performed. Twenty-eight studies from 12 countries were reviewed. While 22 (73%) studies reported high COVID-19 vaccine seroconversion rates in PWH, PWH with lower baseline CD4 counts, CD4/CD8 ratios, or higher baseline viral loads had lower seroconversion rates and immunologic titers. Data on vaccine-induced seroconversion in PWH are reassuring, but more research is needed to evaluate the durability of COVID-19 vaccine responses in PWH.
Respiratory Syncytial Virus Incidence and Severity in a Community-Based Prospective Cohort of Children Aged 0–14 Years
Authors: Smith Matthew , Kubale John , Kuan Guillermina , Ojeda Sergio , Vydiswaran Nivea , Sanchez Nery , Gresh Lionel , Latta Krista , Lopez Roger , Patel May , Balmaseda Angel , Gordon Aubree
Published: November 2022

Background

Respiratory syncytial virus (RSV) is a substantial source of severe illnesses including acute lower respiratory infections (ALRIs) like pneumonia. However, its burden in older children remains less well understood.

Methods

Using a community-based prospective cohort, we assessed the burden of symptomatic reverse-transcription polymerase chain reaction–confirmed RSV among Nicaraguan children aged 0–14 years from 2011 to 2016. ALRI was defined as physician diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyperreactivity.

Results

Between 2011 and 2016, 2575 children participated in the cohort. Of these, 630 (24.5%) had at least 1 episode of symptomatic RSV and 194 (7.5%) had multiple episodes. Subtype was identified in 571 (69.3%) episodes with 408 (71.5%) RSV-A, 157 (27.5%) RSV-B, and 6 (1%) positive for both. Children aged <2 years displayed the highest incidence of symptomatic RSV, with 269.3 cases per 1000 person-years (95% confidence interval [CI], 242.1–299.5). Beyond 2 years, incidence (95% CI) of symptomatic RSV decreased rapidly: 145.6 (129.9–163.1), 37.9 (31.9–45.0), and 19.3 (14.9–25.0) cases per 1000 person-years among children aged 2–4, 5–9, and 10–14 years, respectively. Incidence of RSV-associated ALRI was highest in children aged <2 years (85.95 per 1000 person-years [95% CI, 71.30–103.61]): 2.1, 9.5, and 17.3 times that of participants aged 2–4, 5–9, and 10–14 years, respectively. Children <2 years old were significantly more likely to have an RSV-associated hospitalization (P < .001).

Conclusions

There is a substantial burden of symptomatic and severe RSV in children. While older children did present with RSV, the rates of symptomatic and severe RSV decreased by as much as 95% beyond age 5.
Sleep disparities in the first month of college: implications for academic achievement
Authors: Bermudez Vanessa N , Fearon-Drake Danielle , Wheelis Meaghann , Cohenour Michelle , Suntai Zainab , Scullin Michael K
Published: November 2022

Study Objective

We investigated sleep disparities and academic achievement in college.

Methods

Participants were 6,002 first-year college students attending a midsize private university in the southern United States [62.0% female, 18.8% first-generation, 37.4% Black, Indigenous, or People of Color (BIPOC) students]. During the first 3–5 weeks of college, students reported their typical weekday sleep duration, which we classified as short sleep (<7 hours), normal sleep (7–9 hours), or long sleep (>9 hours).

Results

The odds for short sleep were significantly greater in BIPOC students (95% CI: 1.34–1.66) and female students (95% CI: 1.09–1.35), and the odds for long sleep were greater in BIPOC students (95% CI: 1.38–3.08) and first-generation students (95% CI: 1.04–2.53). In adjusted models, financial burden, employment, stress, STEM academic major, student athlete status, and younger age explained unique variance in sleep duration, fully mediating disparities for females and first-generation students (but only partially mediating disparities for BIPOC students). Short and long sleep predicted worse GPA across students’ first year in college, even after controlling for high school academic index, demographics, and psychosocial variables.

Conclusions

Higher education should address sleep health early in college to help remove barriers to success and reduce disparities.
Effect of benzoic acid with or without a Bacillus-based direct-fed microbial on the performance and carcass merit of grow-finish pigs
Authors: Humphrey D C , Bergstrom J R , Perez-Calvo E , Greiner L L
Published: November 2022

Two hundred and forty barrows and gilts (DNA 600 X 241, DNA Genetics, Columbus, NE) with an initial body weight (BW) of 35.5 ± 4.2 kg were sorted into split-sex pens, blocked by initial body weight, and randomly allocated to one of three dietary treatments with eight pigs per pen and ten pens per treatment. Dietary treatments included a standard diet (CON), CON plus 0.3% benzoic acid (BA; VevoVitall, DSM Nutritional Products, Parsippany, NJ), and CON plus 0.3% BA and 0.025% Bacillus-based direct-fed microbial (BA+DFM; PureGro, DSM Nutritional Products, Parsippany, NJ). The experimental diets were fed in four feeding phases. Pigs were weighed and feed intake measured at the beginning and end of each phase for the calculation of average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Additionally, ultra-sound was utilized at the conclusion of the trial on day 81 for measurements of backfat and loin eye area. Data were analyzed as repeated measures in SAS 9.4 (SAS Institute, Cary, NC) with fixed effects of treatment, phase, sex, and block included in the model. Pen was the experimental unit, and results were considered significant if P ≤ 0.05 and a tendency if 0.05 < P ≤ 0.10. Overall, pigs fed BA had increased ADFI compared to pigs fed CON (2.88 vs. 2.75 kg, P = 0.015), while pigs fed BA+DFM had similar ADFI compared to pigs fed CON or BA (P ≥ 0.279). There was a tendency for an effect of dietary treatment on ADG (P = 0.063), where pigs fed BA tended to grow faster than pigs fed CON (1.11 vs. 1.08 kg, P = 0.051); however, there were no differences in feed efficiency between treatments (P = 0.450). Additionally, there was no evidence for an effect of dietary treatment on pig BF or LEA (P ≥ 0.334). In conclusion, supplementing 0.3% benzoic acid to grow-finish pigs stimulated feed intake, but did not affect efficiency, or carcass merit.
Radiographic Parameters in Cervical Myelopathy
Authors: Waddell William H. , Vaughan Wilson E. , Abtahi Amir M.
Published: November 2022

Study Design:

This was a narrative review.

Objectives:

Provide a comprehensive review of radiographic alignment parameters and their effect on procedure selection, surgical decision-making, and clinical outcomes for the treatment of cervical spondylotic myelopathy (CSM).

Summary of Background Data:

The use of radiographic parameters to predict prognosis and surgical outcomes in patients with CSM is an evolving field given the complex presentation of patients with this condition.

Methods:

A literature search was conducted using PubMed for surgical treatment of CSM, with an emphasis on cervical radiographic parameters and clinical outcomes.

Results:

The principal goals of spine surgery can be broken down into decompression, stabilization, and restoration of alignment. The principle of restoring balance takes careful preoperative planning and attention to radiographic parameters including cervical lordosis, C2–C7 sagittal vertical axis, neck tilt, thoracic inlet angle, T1 slope, K-line, and modified K-line. Surgical interventions for CSM include anterior cervical discectomy and fusion, posterior cervical fusion, or laminoplasty and careful consideration of radiographic measures guide surgical decision-making is essential to ensure optimal outcomes.

Conclusion:

Utilization of key radiographic parameters in surgical planning and decision-making allows surgeons to optimize clinical outcomes for CSM.

Level of Evidence:

Level V.
Proliferating Pilar Tumors Are Characterized by Recurrent 15q, 6q, and 6p22.2 Alterations
Authors: Fischer Grant M. , Lindeman Neal I. , Ligon Azra H. , Russell-Goldman Eleanor
Published: November 2022

Proliferating pilar tumors (PPTs) are rare neoplasms of external root sheath derivation, which most commonly occur on the scalp of elderly women. Although typically showing classic histologic features such as trichilemmal type keratinization, a lobular architecture and peripheral palisading, squamous cell carcinoma (SCC) remains a common diagnostic pitfall. Therefore, we sought to explore the molecular pathogenesis of PPTs and compare it with that of cutaneous squamous cell carcinoma (cSCC). Herein, we describe the use of a next-generation DNA sequencing platform to provide the most comprehensive molecular genetic analysis to date of a cohort of 5 PPTs and compare them to 5 head and neck cutaneous SCCs. Recurrent broad arm-level gains of 15q and concurrent single-copy losses of 6q and 6p22.2 were observed in 4 of 5 (80%) PPT cases. Other recurrent mutations or alterations of significance were not found in PPTs. Notably, these chromosomal changes were not identified in any of the 5 cutaneous SCCs, which instead showed recurrent alterations in the known SCC driver genes TP53, CDKN2A, and NOTCH1. Here, we show for the first time that PPTs are molecularly distinct from cutaneous SCC and provide evidence that recurrent alterations in chromosome 15 and chromosome 6 are central to the pathogenesis of PPTs.
Machine Learning Analysis of the Cerebrovascular Thrombi Lipidome in Acute Ischemic Stroke
Authors: Martha Sarah R. , Levy Samuel H. , Federico Emma , Levitt Michael R. , Walker Melanie
Published: November 2022

OBJECTIVE: The aim of this study was to identify a signature lipid profile from cerebral thrombi in acute ischemic stroke (AIS) patients at the time of ictus. METHODS: We performed untargeted lipidomics analysis using liquid chromatography-mass spectrometry on cerebral thrombi taken from a nonprobability, convenience sampling of adult subjects (≥18 years old, n = 5) who underwent thrombectomy for acute cerebrovascular occlusion. The data were classified using random forest, a machine learning algorithm. RESULTS: The top 10 metabolites identified from the random forest analysis were of the glycerophospholipid species and fatty acids. CONCLUSION: Preliminary analysis demonstrates feasibility of identification of lipid metabolomic profiling in cerebral thrombi retrieved from AIS patients. Recent advances in omic methodologies enable lipidomic profiling, which may provide insight into the cellular metabolic pathophysiology caused by AIS. Understanding of lipidomic changes in AIS may illuminate specific metabolite and lipid pathways involved and further the potential to develop personalized preventive strategies.
Herpes Zoster in Hospitalized Patients With Inflammatory Bowel Disease
Authors: Guerrero Vinsard Daniela , Wakefield Dorothy , Karagozian Raffi , Farraye Francis A.
Published: November 2022

Background:

Studies have demonstrated an increased risk of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD). Most recently, the Advisory Committee on Immunization Practices recommended HZ vaccination for adults aged 19 years and older who are at increased risk of shingles due to their disease or drug-related immunosuppression. We aimed to assess the burden of HZ in IBD inpatients and contribute with scientific evidence for an appropriate age cut-off vaccination recommendation.

Materials and Methods:

Population-based cross-sectional analysis using the 2014 US National Inpatient Sample (NIS). We measured the frequencies and demographics of adult patients with IBD admitted to the hospital with an HZ diagnosis. Age-stratification analysis was performed, and age groups were compared with non-IBD inpatients with an HZ diagnosis.

Results:

From 307,260 IBD discharges, 1110 (0.35%) patients were found to have HZ as follows: shingles 63%; post-herpetic neuralgia 26%; HZ with ophthalmic involvement 7%; HZ with neurological involvement 4%. Women with IBD were more likely to have shingles (P=0.002) and post-herpetic neuralgia (P=0.001) than men with IBD. The shingles distribution by age in IBD inpatients was 18 to 39 (13%), 40 to 49 (19%), 50 to 59 (18%), 60 to 99 (50%) compared with 18 to 39 (8%), 40 to 49 (6%), 50 to 59 years (14%), 60 to 99 (72%) in non-IBD inpatients (P=0.0004).

Conclusions:

Hospitalized patients with IBD were found to have a higher frequency of shingles at younger ages when compared with hospitalized patients without IBD. Shingles is more frequent in women, and their prevalence steadily increases with aging though 32% of cases were seen in patients younger than age 50.
Clinical evidence supporting cefiderocol for serious Acinetobacter baumannii infections
Authors: Bassetti Matteo , Vena Antonio , Castaldo Nadia , Giacobbe Daniele Roberto , Peghin Maddalena , Grossi Paolo Antonio
Published: November 2022

Purpose of review

Nosocomial infections caused by Acinetobacter baumannii currently represent a serious challenge for clinicians because treatment options are limited and frequently associated with significant toxicity. Cefiderocol is a first-in-class siderophore cephalosporin that has a proven efficacy for the treatment of multidrug-resistant Gram-negative infections, including carbapenem-resistant A. baumannii. The aim of this review is to evaluate the current evidence for the role of cefiderocol in the management of A. baumannii infections.

Recent findings

In this review, we briefly summarize the available data on the efficacy (from randomized controlled trials) and on effectiveness and cure rates (from observational studies), pertaining to the use of cefiderocol for treatment of serious A. baumannii infections.

Cefiderocol represents a promising and safe antibiotic option for treating patients with carbapenem-resistant A. baumannii infections. Due to conflicting mortality data from available experience, well-designed future randomized controlled trials and real-life studies are needed.
Treatment of left ventricular dysfunction in dilated cardiomyopathy with a myeloperoxidase inhibitor
Authors: Geissen Simon , Braumann Simon , Adler Joana , Nettersheim Felix Sebastian , Mehrkens Dennis , Hof Alexander , Guthoff Henning , Stein Philipp von , Witkowski Sven , Gerdes Norbert , Isermann Lea , Trifunovic Aleksandra , Bunck Alexander C. , Mollenhauer Martin , Winkels Holger , Adam Matti , Klinke Anna , Hellmich Martin , Kelm Malte , Rudolph Volker , Rosenkranz Stephan , Baldus Stephan
Published: November 2022

Dilated cardiomyopathy (DCM), an incurable disease of the cardiomyocyte terminating in systolic heart failure (HFrEF), is prevalent, causes hospitalization and is associated with increased mortality. Despite evidence of immune activation in DCM, anti-inflammatory interventions so far did not prove to alter the course of this disease. Here we show that myeloperoxidase (MPO), the principal heme peroxidase expressed by polymorphonuclear neutrophils (PMN) and monocytes, critically contributes to HFrEF in DCM.

Muscle LIM protein (MLP) deficient mice, which spontaneously develop DCM, display increased circulating PMN counts and augmented levels of vessel-immobilized MPO. Genetic ablation and pharmacological inhibition of MPO resulted in enhanced nitric oxide (NO) bioavailability of systemic conductance and resistance vessels, and subsequently restoration of systolic left ventricular (LV) function, whereas infusion of MPO worsened systolic LV function. When patients diagnosed for DCM were treated with an orally available MPO inhibitor, systolic LV function increased, natriuretic peptides declined, and functional status improved.

Impairment of endothelial NO bioavailability by release of leukocyte-derived MPO evolves as a disease-aggravating mechanism in DCM. MPO inhibition profoundly improved ventricular function by lowering systemic vascular resistance and thus holds promise as a novel and complementary treatment strategy for patients with DCM.
A ten-year microbiological study ofPseudomonas aeruginosastrains revealed diffusion of carbapenems and quaternary ammonium compounds resistant populations
Authors: Pottier Marine , Gravey François , Castagnet Sophie , Auzou Michel , Bénédicte Langlois , Guérin François , Giard Jean-Christophe , Léon Albertine , Hello Simon Le
Published: November 2022

Pseudomonas aeruginosais one of the leading causes of healthcare-associated infections. For this study, the susceptibility profiles to antipseudomonal antibiotics and a quaternary ammonium compound, didecyldimethylammonium chloride (DDAC), widely used as a disinfectant, were established for 180 selected human and environmental hospital strains isolated between 2011 and 2020. Furthermore, a genomic study was performed to determine their resistome and clonal putative relatedness. During the ten-year study period, it was estimated that 9.5% of clinicalP. aeruginosawere resistant to carbapenem, 11.9% presented an MDR profile, and 0.7% an XDR. Decreased susceptibility (DS) to DDAC was observed for 28.0% of strains that was significantly more associated with MDR and XDR profiles and from hospital environmental samples (p <0.0001). According to genomic analyses, theP. aeruginosapopulation unsusceptible to carbapenems and/or to DDAC was diverse but mainly belonged to top ten high-risk clones described worldwide. The carbapenem resistance appeared mainly due to the production of the VIM-2 carbapenemase (39.3%) and DS to DDAC mediated by MexAB-OprM pump efflux overexpression. This study highlights the diversity of MDR/XDR populations ofP. aeruginosawhich are unsusceptible to molecules that are widely used in medicine and hospital disinfection and are probably distributed in hospitals worldwide.
Exploiting Embryonic Niche Conditions to Grow Wilms Tumor Blastema in Culture
Authors: Wojcik Heather M. , Lovvorn Harold N. , Hollingshead Melinda , Pierce Janene , Stotler Howard , Murphy Andrew J. , Borgel Suzanne , Phelps Hannah M. , Correa Hernan , Perantoni Alan O.
Published: November 2022

Wilms Tumor (WT), or nephroblastoma, is the most common pediatric kidney cancer. Most WTs display a “favorable” triphasic histology, in which the tumor is comprised of blastemal, stromal, and epithelial cell types. Blastemal predominance after neoadjuvant chemotherapy or diffuse anaplasia (“unfavorable” histology; 5-8%) portend a worse prognosis. Blastema likely provide the putative cancer stem cells (CSCs), which retain molecular and histologic features characteristic of nephron progenitor cells (NPCs), within WTs. NPCs arise in the metanephric mesenchyme (MM) and populate the cap mesenchyme (CM) in the developing kidney. WT blastemal cells, like NPCs, similarly express markers, SIX2 and CITED1. Tumor xenotransplantation is currently the only dependable method to propagate tumor tissue for research or therapeutic screening, since efforts to culture tumorsin vitroas monolayers have invariably failed. Therefore, a critical need exists to propagate WT stem cells rapidly and efficiently for high-throughput, real-time drug screening. Previously, our lab developed niche conditions that support the propagation of murine NPCs in culture. By applying similar conditions to WTs, we have successfully expanded and passaged WT cells from five distinct untreated patient tumors and maintained key NPC “stemness” markers, SIX2, NCAM and YAP1, and CSC marker ALDH1. These findings suggest that our culture conditions sustain the WT blastemal population, as previously shown for normal NPCs. As a result, we have developed new WT cell lines and a multi-passagein vitromodel for studying the blastemal lineage/CSCs in WTs. Furthermore, this system supports growth of heterogeneous WT cells, upon which potential drug therapies could be tested for efficacy and resistance.
Discovery of benzo[c]phenanthridine derivatives with potent activity against multidrug resistantMycobacterium tuberculosis
Authors: Sun Zhiqi , Liang Yi Chu , Lu Chen , Lupien Andréanne , Xu Zhongliang , Berton Stefania , Behr Marcel A. , Yang Weibo , Sun Jim
Published: November 2022

Mycobacterium tuberculosis(Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug-resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug resistant (MDR) Mtb strains. Herein, we design and synthesize 35 novelbenzo[c]phenanthridinederivatives (BPD). The two most potent compounds, BPD-6 and BPD-9, accumulated within the bacterial cell and exhibited strong inhibitory activity (MIC90∼ 2-10 μM) against multipleMycobacteriumstrains, while remaining inactive against a range of other Gram-negative and Gram-positive bacteria. BPD-6 and BPD-9 were also effective in reducing Mtb viability within infected macrophages. The two BPD compounds displayed comparable efficacy to rifampicin, a critical frontline antibiotic used for the prevention and treatment of TB. Importantly, BPD-6 and BPD-9 inhibited the growth of multiple MDR Mtb clinical isolates, suggesting a completely novel mechanism of action compared to existing frontline TB dugs. The discovery of BPDs provides novel chemical scaffolds for anti-TB drug discovery.

TOC/GRAPHICAL ABSTRACT
Transcutaneous Vagus Nerve Stimulation in the Treatment of Long Covid-Chronic Fatigue Syndrome
Authors: Natelson Benjamin H , Blate Michelle , Soto Tiffany
Published: November 2022

Many patients do not recover following Covid infection. The resulting illness is called Long Covid. Because there is no agreed upon treatment for this ailment, we decided to do an open label pilot study using non-invasive, transcutaneous stimulation of the auricular branch of the vagus nerve. Inclusion criteria required the patient to fulfill criteria for having chronic fatigue syndrome. Fourteen patients provided evaluable data. Eight of these fulfilled our requirements for treatment success. Since our criterion for a successful study was that at least a third of patients had to show a positive response to treatment, this was a successful pilot that warrants a follow up study that is appropriately sham controlled.

All authors have read and approved this manuscript for submission.

There are no competing interests and support for doing this study was via patient donations to support Dr Natelson’s research activities.

The actual data summarized in Table 1 are available upon request
Crystal structure of a heterotrimetallic 12-metallacrown-4 with 2-propylvalerate anion bridges
Authors: Aziz Ozha A. , Zeller Matthias , Zaleski Curtis M.
Published: November 2022

The synthesis and single-crystal X-ray structure for tetraaquatetrakis(μ-2-propylvalerato)tetrakis(μ4-salicylhydroximato)dysprosiumtetramanganesesodium dimethylformamide tetrasolvate, [DyMn4Na(C7H4NO3)4(C8H15O2)4(H2O)4]·4C3H7NO or DyNa(2-PV)4[12-MCMnIII
Nshi-4](H2O)4·4DMF, 1, where MC is metallacrown, shi3− is salicylhydroximate, 2-PV is 2-propylvalerate, and DMF is N,N-dimethylformamide, is reported. The slightly domed metallamacrocycle contains four ring MnIII ions and four shi3− ligands that generate an [MnIII—N—O] repeat unit that recurs four times. The ring MnIII ions are five-coordinate with a square-pyramidal shape. Furthermore, the metallacrown binds both a DyIII ion and a Na+ ion in the central cavity. The central ions are located on opposite faces of the cavity with the DyIII ion located on the convex side of the MC and the Na+ ion located on the concave side. Each central ion is eight-coordinate although they possess different geometries. The DyIII ion has a square-antiprismatic shape, while the Na+ ion has an extremely distorted biaugmented trigonal–prismatic shape. The four 2-propylvalerate anions help to tether the DyIII to the MC cavity by forming bridges between the DyIII ion and each ring MnIII ion. Moreover, the interstitial DMF molecules are hydrogen bonded to the water molecules that complete the coordination environment of the Na+ ion. The metallacrown framework (excluding the DyIII and Na+ ions), the bridging 2-propylvalerate, and the interstitial DMF molecule experience whole-molecule disorder due to the rotational orientation of the metallamacrocycle. Additionally, the main moiety alkyl chain of the 2-propylvalerate is disordered over two additional orientations, and the main moiety interstitial DMF molecule is disordered over one additional orientation. The main moiety of the metallacrown framework refined to 0.9030 (14), while the minor B-moiety refined to 0.0971 (14). The main moiety alkyl chain of the 2-propylvalerate refined to 0.287 (3): 0.309 (3): 0.307 (3), and the minor B-moiety alkyl chain refined to 0.0971 (14). Lastly, the main moiety interstitial DMF refined to 0.549 (3): 0.354 (3), and the minor B-moiety DMF refined to 0.0971 (14).
Structural characterization and antimycobacterial evaluation of a benzimidazole analogue of the antituberculosis clinical drug candidate TBA-7371
Authors: Richter Adrian , Goddard Richard , Schönefeld Roy , Imming Peter , Seidel Rüdiger W.
Published: November 2022

The crystal structure and in vitro antimycobacterial properties of N-(2-fluoroethyl)-1-[(6-methoxy-5-methylpyrimidin-4-yl)methyl]-1H-benzo[d]imidazole-4-carboxamide (C17H18FN5O2, 1), a previously reported benzimidazole analogue of the 1,4-azaindole-based antituberculosis drug candidate TBA-7371, are reported. The structure determination was achieved using Hirshfeld atom refinement. Compound 1 crystallizes in the triclinic system (space group P\overline{1}) with two molecules in the asymmetric unit (Z′ = 2). The two crystallographically distinct molecules exhibit a similar conformation with the amide groups in a Z conformation, forming an intramolecular Namide—H...Nbenzimidazole hydrogen bond. The most significant supramolecular feature in the solid-state is a relatively short Cbenzimidazole—H...Npyrimidine hydrogen bond. Antimycobacterial testing confirmed in vitro activity against Mycobacterium smegmatis, but no growth inhibtion of Mycobacterium abscessus was found.
Firm age and Chinese firms’ OFDI in developing and developed countries: the moderating roles of industry munificence and state ownership
Authors: Xie Qunyong
Published: November 2022

Purpose

Applying the internationalization process model (IPM) and the strategic fit perspective, this research aims to test the effects of firm age on Chinese firms’ outward foreign direct investment (OFDI) in developing and developed countries.

Design/methodology/approach

Using data on some Chinese firms, this study applied the zero-inflated negative binomial model and Heckman two-stage model to do the analyses.

Findings

This research found that firm age has different effects on Chinese firms’ OFDI in developed and developing countries. State ownership and industry munificence independently and jointly can moderate these effects.

Originality/value

This study contributes to the IPM and solves the theoretical conflict about the firm age–OFDI relationship.
Flexible human resource management systems and employee innovation performance in China – based on the moderated mediation effect
Authors: Xu Yan , Qian Han , Zhang Min , Tian Feng , Zhou Lulu , Zhao Shuming
Published: November 2022

Purpose

This paper aims to explore the impact of flexible human resource management system (FHRMS) on employee innovation performance in Chinese context. The boundary conditions of employability and organizational identity are also discussed.

Design/methodology/approach

This study is based on 322 questionnaire survey from employees in China. The questionnaires were collected at two time points. This study used the method of multi-level linear model analysis for empirical test.

Findings

This study has three conclusions. First, FHRMS have a significant positive impact on employee innovation performance, with employability playing a mediating role. Second, organizational identity plays a moderating role between employability and employee innovation performance. Third, organizational identity moderates the mediating effect of a human source management systems on employee innovation performance through employability.

Originality/value

The results are helpful to open the “black box” of the influence of FHRMS on employees’ individual innovation performance. This study provides a reference for enterprises to establish flexible human source management system to improve employee innovation performance.