bluuebunny/crossref_metadata_2025 huggingface dataset:
General Practitioners perspectives on infant telomere length screening after a pregnancy complication: a qualitative analysis
Authors: Puglisi Carolyn J , McDonough Joshua , Bianco-Miotto Tina , Grieger Jessica A
Published: June 2023

Background

Pregnancy complications can impact the mother and child’s health in the short and longterm resulting in an increased risk of chronic disease later in life. Telomere length is a biomarker of future cardiometabolic diseases and may offer a novel way of identifying offspring most at risk for future chronic diseases.

Objective(s)

To qualitatively explore General Practitioners’ (GPs) perspectives on the feasibility and uptake for recommending a telomere screening test in children who were born after a pregnancy complication.

Methods

Twelve semi-structured interviews were conducted with GPs within metropolitan Adelaide, South Australia. Interviews were audio recorded, transcribed verbatim, and analysed for codes and themes.

Results

Two themes were generated: ethical considerations and practical considerations. Ethically, the GP participants discussed barriers including consenting on behalf of a child, parental guilt, and the impact of health insurance, whereas viewing it for health promotion was a facilitator. For practical considerations, barriers included the difficulty in identifying people eligible for screening, maintaining medical communication between service providers, and time and financial constraints, whereas linking screening for telomere length with existing screening would facilitate uptake.

Conclusions

GPs were generally supportive of potential telomere screening in infants, particularly via a saliva test that could be embedded in current antenatal care. However, several challenges, such as lack of knowledge, ethical considerations, and time and financial constraints, need to be overcome before such a test could be implemented into practice.
Mob4 is essential for spermatogenesis in Drosophila melanogaster
Authors: Santos Inês B , Wainman Alan , Garrido-Maraver Juan , Pires Vanessa , Riparbelli Maria Giovanna , Kovács Levente , Callaini Giuliano , Glover David M , Tavares Álvaro A
Published: June 2023

Gamete formation is essential for sexual reproduction in metazoans. Meiosis in males gives rise to spermatids that must differentiate and individualize into mature sperm. In Drosophila melanogaster, individualization of interconnected spermatids requires the formation of individualization complexes that synchronously move along the sperm bundles. Here, we show that Mob4, a member of the Mps-one binder family, is essential for male fertility but has no detectable role in female fertility. We show that Mob4 is required for proper axonemal structure and its loss leads to male sterility associated with defective spermatid individualization and absence of mature sperm in the seminal vesicles. Transmission electron micrographs of developing spermatids following mob4RNAi revealed expansion of the outer axonemal microtubules such that the 9 doublets no longer remained linked to each other and defective mitochondrial organization. Mob4 is a STRIPAK component, and male fertility is similarly impaired upon depletion of the STRIPAK components, Strip and Cka. Expression of the human Mob4 gene rescues all phenotypes of Drosophila mob4 downregulation, indicating that the gene is evolutionarily and functionally conserved. Together, this suggests that Mob4 contributes to the regulation of the microtubule- and actin-cytoskeleton during spermatogenesis through the conserved STRIPAK complex. Our study advances the understanding of male infertility by uncovering the requirement for Mob4 in sperm individualization.
Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial
Authors: Sojo-Dorado Jesús , López-Hernández Inmaculada , Hernández-Torres Alicia , Retamar-Gentil Pilar , Merino de Lucas Esperanza , Escolà-Vergé Laura , Bereciartua Elena , García-Vázquez Elisa , Pintado Vicente , Boix-Palop Lucía , Natera-Kindelán Clara , Sorlí Luisa , Borrell Nuria , Amador-Prous Concha , Shaw Evelyn , Jover-Saenz Alfredo , Molina Jose , Martínez-Álvarez Rosa M , Dueñas Carlos J , Calvo-Montes Jorge , Lecuona María , Pomar Virginia , Borreguero Irene , Palomo-Jiménez Virginia , Docobo-Pérez Fernando , Pascual Álvaro , Rodríguez-Baño Jesús
Published: June 2023

Background

Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec).

Methods

Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5–7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders.

Results

Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, −2.2; 95% CI: −17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42–3.29, P = 0.75). No relevant differences in adverse events were seen.

Conclusions

Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.
Hidden lymphoma in the appendix: a case of primary appendiceal diffuse large B-cell lymphoma presenting as acute appendicitis
Authors: Solis-Pazmino Paola , Vasques Luana , Maldonado Pedro , Lunardi João Dias , Schneider Mateus , Gorgen Andre
Published: June 2023

The occurrence of diffuse large B-cell lymphoma (DLBCL) of the appendix presenting as acute appendicitis is rare, constituting only a minuscule portion (0.015%) of gastrointestinal lymphoma cases. We present a case of a 55-year-old woman that was admitted to the emergency department with symptoms of acute appendicitis and underwent an interval laparoscopic appendectomy with a right hemicolectomy and lymph node resection. Pathological examination revealed the presence of DLBCL in the appendix. The patient is undergoing chemotherapy.
Prevalence of non-stationarity in quasi-periodic pulsations (QPPs) associated with M- and X-class solar flares
Authors: Mehta T , Broomhall A-M , Hayes L A
Published: June 2023

Quasi-periodic pulsations (QPPs) are frequently observed in solar and stellar flare emission, with recent studies suggesting that an increasing instantaneous period is a common characteristic of QPPs. Determining the prevalence of non-stationarity in QPPs contributes to a better understanding of which mechanism(s) is (are) responsible in QPP generation. We obtain the rate of period evolution from QPPs in 98 M- and X-class flares from Solar Cycle 24 with average periods between 8 and 130 s and investigate the prevalence of QPP non-stationarity. We also investigate whether the presence of a coronal mass ejection (CME) impacts the period evolution of QPPs. We analyse soft X-ray light curves obtained from GOES’ X-ray sensor (XRS) and assess the dominant periods in the impulsive and decay phases of the flares using the fast Fourier transform. We relate the rate of period evolution to flare duration, peak flare energy, and average QPP period. We find evidence of non-stationarity in 81 per cent of the flares assessed, with most QPPs exhibiting a period evolution of ≤10 s between the impulsive and decay phases, of which 66 per cent exhibited an apparent period growth and 14 per cent showed an apparent period shrinkage. We find a positive correlation between the absolute magnitude of period evolution and the duration of the flare and no correlation between the period evolution of the QPPs and flare energy or CME presence. Furthermore, we conclude that non-stationarity is common in solar QPPs and must be accounted for in flare analysis.
Nsp14 of SARS-CoV-2 inhibits mRNA processing and nuclear export by targeting the nuclear cap-binding complex
Authors: Katahira Jun , Ohmae Tatsuya , Yasugi Mayo , Sasaki Ryosuke , Itoh Yumi , Kohda Tomoko , Hieda Miki , Yokota Hirai Masami , Okamoto Toru , Miyamoto Yoichi
Published: June 2023

To facilitate selfish replication, viruses halt host gene expression in various ways. The nuclear export of mRNA is one such process targeted by many viruses. SARS-CoV-2, the etiological agent of severe acute respiratory syndrome, also prevents mRNA nuclear export. In this study, Nsp14, a bifunctional viral replicase subunit, was identified as a novel inhibitor of mRNA nuclear export. Nsp14 induces poly(A)+ RNA nuclear accumulation and the dissolution/coalescence of nuclear speckles. Genome-wide gene expression analysis revealed the global dysregulation of splicing and 3′-end processing defects of replication-dependent histone mRNAs by Nsp14. These abnormalities were also observed in SARS-CoV-2-infected cells. A mutation introduced at the guanine-N7-methyltransferase active site of Nsp14 diminished these inhibitory activities. Targeted capillary electrophoresis-mass spectrometry analysis (CE-MS) unveiled the production of N7-methyl-GTP in Nsp14-expressing cells. Association of the nuclear cap-binding complex (NCBC) with the mRNA cap and subsequent recruitment of U1 snRNP and the stem-loop binding protein (SLBP) were impaired by Nsp14. These data suggest that the defects in mRNA processing and export arise from the compromise of NCBC function by N7-methyl-GTP, thus exemplifying a novel viral strategy to block host gene expression.
Common mental disorder and suicidality among doctors: differences by specialty
Authors: Petrie K , Sanatkar S , Shand F , Harvey S B
Published: June 2023

Background

Common mental disorders (CMDs) and suicidal ideation (SI) are prevalent among doctors, yet limited evidence exists investigating the relationship of specialty area to these outcomes.

Aims

This study aimed to determine the prevalence of likely CMD and SI among doctors and to investigate whether likelihood of these outcomes varied by area of medical specialty.

Methods

A secondary analysis of a representative national survey of 12,252 Australian doctors was conducted. Demographic and work-related variables, SI and CMD (GHQ-28), were assessed among doctors (n = 7037; 57%) working in a range of specialty areas. Logistic regression was used to examine the association between specialty and mental health outcomes in unadjusted and adjusted models.

Results

Almost one-quarter of doctors (n = 1560; 23%) reported symptom levels indicating likely CMD whilst 9% (n = 667) reported SI in the last year. Doctors in surgery (adjusted odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.54–0.97, P = 0.03) were at significantly lower risk of CMD than General Practitioners (GPs), whilst doctors in anaesthetics (adjusted OR = 1.45; 95% CI 1.09–1.93, P = 0.01) and paediatrics (adjusted OR = 1.88; 95% CI 1.02–3.47, P = 0.04) were at significantly higher risk of experiencing SI compared to GPs after accounting for confounders.

Conclusions

Results demonstrated that doctors in Australia working in certain specialties, specifically anaesthetics and paediatrics, were at significantly greater risk of suicidal ideation compared to GPs after accounting for confounders. Interventions to address CMD and SI among doctors in all specialties remain urgently needed.
Six attitudes to promote personal, patient-centred care in an era of addictive technology
Authors: Schattner Ami
Published: June 2023

In contrast with the rapid advances in medical knowledge and technology, the clinical encounter may often appear as perfunctory, impersonal, and unworthy to both patient and practitioner who is often immersed in the computer screen rather than the patient, stressed by improbable time constraints, and often finds deceptive relief in inappropriate test-ordering, prescriptions, and referrals. We suggest routinely adopting six attitudes to achieve a more balanced, personal, and patient-centred encounter: conducting a curiosity-driven encounter; emphasizing humanistic values; performing a complete physical examination; increasing patients' face time; addressing the patient’s health as a whole; and rational test-ordering and judicious prescribing.
A prospective survey on therapeutic inertia in psoriatic arthritis (OPTI’PsA)
Authors: Lioté Frédéric , Constantin Arnaud , Dahan Étienne , Quiniou Jean-Baptiste , Frazier Aline , Sibilia Jean
Published: June 2023

Objectives

Clinical inertia, or therapeutic inertia (TI), is the medical behaviour of not initiating or intensifying treatment when recommended by clinical recommendations. To our knowledge, our survey is the first to assess TI around psoriatic arthritis (PsA).

Methods

Eight hundred and twenty-five French rheumatologists were contacted via email between January and March 2021 and invited to complete an online questionnaire consisting of seven clinical vignettes: five cases (‘oligoarthritis’, ‘enthesitis’, ‘polyarthritis’, ‘neoplastic history’, ‘cardiovascular risk’) requiring treatment OPTImization, and two ‘control’ cases (distal interphalangeal arthritis, atypical axial involvement) not requiring any change of treatment—according to the most recent PsA recommendations. Rheumatologists were also questioned about their routine practice, continuing medical education and perception of PsA.

Results

One hundred and one rheumatologists completed this OPTI’PsA survey. Almost half the respondents (47%) demonstrated TI on at least one of the five vignettes that warranted treatment optimization. The complex profiles inducing the most TI were ‘oligoarthritis’ and ‘enthesitis’ with 20% and 19% of respondents not modifying treatment, respectively. Conversely, clinical profiles for which there was the least uncertainty (‘polyarthritis in relapse’, ‘neoplastic history’ and ‘cardiovascular risk’) generated less TI with 11%, 8% and 6% of respondents, respectively, choosing not to change the current treatment.

Conclusion

The rate of TI we observed for PsA is similar to published data for other chronic diseases such as diabetes, hypertension, gout or multiple sclerosis. Our study is the first to show marked clinical inertia in PsA, and further research is warranted to ascertain the reasons behind this inertia.
A nomogram based on clinical factors and CT radiomics for predicting anti-MDA5+ DM complicated by RP-ILD
Authors: Li Yanhong , Deng Wen , Zhou Yu , Luo Yubin , Wu Yinlan , Wen Ji , Cheng Lu , Liang Xiuping , Wu Tong , Wang Fang , Huang Zixing , Tan Chunyu , Liu Yi
Published: June 2023

Objectives

Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) DM complicated by rapidly progressive interstitial lung disease (RP-ILD) has a high incidence and poor prognosis. The objective of this study was to establish a model for the prediction and early diagnosis of anti-MDA5+ DM-associated RP-ILD based on clinical manifestations and imaging features.

Methods

A total of 103 patients with anti-MDA5+ DM were included. The patients were randomly split into training and testing sets of 72 and 31 patients, respectively. After image analysis, we collected clinical, imaging and radiomics features from each patient. Feature selection was performed first with the minimum redundancy and maximum relevance algorithm and then with the best subset selection method. The final remaining features comprised the radscore. A clinical model and imaging model were then constructed with the selected independent risk factors for the prediction of non-RP-ILD and RP-ILD. We also combined these models in different ways and compared their predictive abilities. A nomogram was also established. The predictive performances of the models were assessed based on receiver operating characteristics curves, calibration curves, discriminability and clinical utility.

Results

The analyses showed that two clinical factors, dyspnoea (P = 0.000) and duration of illness in months (P = 0.001), and three radiomics features (P = 0.001, 0.044 and 0.008, separately) were independent predictors of non-RP-ILD and RP-ILD. However, no imaging features were significantly different between the two groups. The radiomics model built with the three radiomics features performed worse than the clinical model and showed areas under the curve (AUCs) of 0.805 and 0.754 in the training and test sets, respectively. The clinical model demonstrated a good predictive ability for RP-ILD in MDA5+ DM patients, with an AUC, sensitivity, specificity and accuracy of 0.954, 0.931, 0.837 and 0.847 in the training set and 0.890, 0.875, 0.800 and 0.774 in the testing set, respectively. The combination model built with clinical and radiomics features performed slightly better than the clinical model, with an AUC, sensitivity, specificity and accuracy of 0.994, 0.966, 0.977 and 0.931 in the training set and 0.890, 0.812, 1.000 and 0.839 in the testing set, respectively. The calibration curve and decision curve analyses showed satisfactory consistency and clinical utility of the nomogram.

Conclusion

Our results suggest that the combination model built with clinical and radiomics features could reliably predict the occurrence of RP-ILD in MDA5+ DM patients.
Longitudinal Investigation of Auditory Dynamic Range Deficits in Early Psychosis and its Relationship to Negative Symptoms
Authors: Sklar Alfredo L , Matinrazm Sayna , Ren Xi , Chlpka Lydia , Curtis Mark , Coffman Brian A , Salisbury Dean F
Published: June 2023

Background and Hypothesis

Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4–8 months from baseline testing.

Study Design

Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale.

Study Results

Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85–75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = −0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = −0.53) and follow-up (ρ = −0.51).

Conclusion

Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.
Virulence Associations and Global Context of AvrStb6 Genetic Diversity in Iranian Populations of Zymoseptoria tritici
Authors: Rad Sepideh Hatami , Ebrahimi Leila , Croll Daniel
Published: June 2023

Managing pathogen damage in wheat production is important for sustaining yields. Fungal plant pathogen genomes encode many small secreted proteins acting as effectors that play key roles in the successful colonization of host tissue and triggering host defenses. AvrStb6 is the first described Zymoseptoria tritici avirulence effector, which triggers Stb6-mediated immunity in the wheat host in a gene-for-gene manner. Evasion of major resistance factors such as Stb6 challenges deployment decisions on wheat cultivars. In this study, we analyzed the evolution of the AvrStb6 effector in Iranian isolates of Z. tritici. In total, 78 isolates were isolated and purified from 30 infected wheat specimens collected from the East Azerbaijan and Ardabil provinces of Iran. The pathogenicity of all isolates was evaluated on the susceptible wheat cultivar ‘Tajan’. A subset of 40 isolates were also tested for pathogenicity on the resistant cultivar ‘Shafir’ carrying Stb6. Genetic diversity at the AvrStb6 locus was analyzed for 14 isolates covering the breadth of the observed disease severity. The AvrStb6 sequence variation was high, with virulent isolates carrying highly diverse AvrStb6 haplotypes. In an analysis including more than 1,000 additional AvrStb6 sequences from a global set of isolates, we found that virulent isolates carried AvrStb6 haplotypes either clustering with known virulent haplotypes on different continents or constituting previously unknown haplotypes. Furthermore, we found that AvrStb6 variants from avirulent isolates clustered with known avirulent genotypes from Europe. Our study highlights the relevance of AvrStb6 for Z. tritici virulence and the exceptional global diversity patterns of this effector.
Increased Ca2+ signaling through CaV1.2 induces tendon hypertrophy with increased collagen fibrillogenesis and biomechanical properties
Authors: Li Haiyin , Korcari Antonion , Ciufo David , Mendias Christopher L. , Rodeo Scott A. , Buckley Mark R. , Loiselle Alayna E. , Pitt Geoffrey S. , Cao Chike
Published: June 2023

Tendons are tension‐bearing tissues transmitting force from muscle to bone for body movement. This mechanical loading is essential for tendon development, homeostasis, and healing after injury. While Ca2+ signaling has been studied extensively for its roles in mechanotransduction, regulating muscle, bone, and cartilage development and homeostasis, knowledge about Ca2+ signaling and the source of Ca2+ signals in tendon fibroblast biology are largely unknown. Here, we investigated the function of Ca2+ signaling through CaV1.2 voltage‐gated Ca2+ channel in tendon formation. Using a reporter mouse, we found that CaV1.2 is highly expressed in tendon during development and downregulated in adult homeostasis. To assess its function, we generated ScxCre;CaV1.2TS mice that express a gain‐of‐function mutant CaV1.2 in tendon. We found that mutant tendons were hypertrophic, with more tendon fibroblasts but decreased cell density. TEM analyses demonstrated increased collagen fibrillogenesis in the hypertrophic tendons. Biomechanical testing revealed that the hypertrophic tendons display higher peak load and stiffness, with no changes in peak stress and elastic modulus. Proteomic analysis showed no significant difference in the abundance of type I and III collagens, but mutant tendons had about two‐fold increase in other ECM proteins such as tenascin C, tenomodulin, periostin, type XIV and type VIII collagens, around 11‐fold increase in the growth factor myostatin, and significant elevation of matrix remodeling proteins including Mmp14, Mmp2, and cathepsin K. Taken together, these data highlight roles for increased Ca2+ signaling through CaV1.2 on regulating expression of myostatin growth factor and ECM proteins for tendon collagen fibrillogenesis during tendon formation.
Neonatal Outcomes after Medications for Opioid Use Disorder during Pregnancy in a State Women’s Prison Facility, 2016–2019
Authors: Knittel Andrea K. , Swartzwelder Rita A. , Zarnick Samantha , Tsujimoto Tamy Moraes , Horne Timeli , Lin Feng Chang , Edwards James , Amos Elton , Alexander James , Thorp John , Jones Hendree E.
Published: June 2023

Objective

Although medications for opioid use disorder improve both maternal and neonatal outcomes, little is known about opioid-exposed infants born during episodes of incarceration. The study sought to examine birth outcomes for infants born with opioid exposure during perinatal incarceration.

Methods

Participants were identified from clinic rosters in a Southeastern women’s prison (2016–2019). Included infants born to pregnant people with opioid use disorder incarcerated in the study facility at the time of delivery. We abstracted hospital length of stay, neonatal opioid withdrawal syndrome (NOWS) severity, and discharge plan from hospital records and report descriptive statistics, analysis of variance F tests, and chi-square tests to compare outcomes by opioid exposure type.

Results

There were 125 infants born after exposure to methadone (n = 34), buprenorphine (n = 15), oxycodone (n = 22), or no opioid medication (n = 54) during prenatal incarceration. Most infants exposed to methadone or buprenorphine had difficulty with eating, sleeping, or consoling (97% and 80%), and 59% and 47% were treated with medication for NOWS, respectively. The majority with prenatal opioid exposure required intervention for NOWS symptoms after their birthing parent was discharged to the prison. The average hospital length of stay was different for infants with no opioid, methadone, buprenorphine, and oxycodone exposure during incarceration (4, 15, 12, and 9 days, respectively, P < 0.001).

Conclusions

Neonatal hospitalization experiences of infants with perinatal opioid exposures during maternal incarceration mirror those of similarly exposed infants born outside the context of incarceration, except for hospital length of stay. Consideration of avoiding separation of the parent-infant dyad may be needed to improve outcomes for these infants.
FOXM1/NCAPH activates glycolysis to promote colon adenocarcinoma stemness and 5-FU resistance
Authors: Lei Yuehua , Wang Dengchao , Chen Wenxing , Tian Xiaojun , Wei Jian
Published: June 2023

Chemotherapy using 5-fluorouracil (5-FU) is currently considered the most effective treatment for advanced colon adenocarcinoma (COAD). However, drug resistance remains a major obstacle in treating COAD. Non-SMC condensin I complex subunit H (NCAPH) is known to have a certain impact on the development of COAD, but its precise involvement in the mechanism of 5-FU resistance has not been demonstrated. Bioinformatics analysis was utilized to assay the expression of NCAPH and Forkhead box M1 (FOXM1) in COAD tumor tissues, which was then verified in COAD cell lines. The resistance of COAD cells to 5-FU was measured by CCK-8 assay, stemness was tested by cell sphere formation assay, and glycolysis ability was measured by cellular energy analysis metabolism. Chromatin Immunoprecipitation and dual-luciferase reporter assays were done to confirm the specific interaction between FOXM1 and NCAPH. The expression levels of FOXM1 and NCAPH were significantly upregulated in COAD tissues and cells, and they were involved in regulating the glycolytic signaling pathway. Inhibition of the glycolytic pathway could reverse the effect of NCAPH overexpression on COAD stemness and resistance. FOXM1 was identified as a transcription factor of NCAPH, and it regulated COAD glycolysis, cell stemness, and 5-FU resistance by activating NCAPH expression. FOXM1-mediated upregulation of NCAPH expression promoted COAD cell stemness and resistance via the glycolytic pathway. This study provides a possible mechanism for the FOXM1/NCAPH axis in the glycolytic pathway, cell stemness, and resistance in COAD.
Predictive value of estimated pulse wave velocity with all-cause and cause-specific mortality in the hypertensive population: the National Health and Nutrition Examination Surveys 1999–2014
Authors: Cheng Wenke , Xu Wei , Luan Sisi , Wen Grace , Kong Fanliang
Published: June 2023

Background:

Estimated pulse wave velocity (ePWV) has been proposed as a potential approach to assess carotid–femoral pulse wave velocity (cfPWV). However, the potential ability of ePWV to predict all-cause and cause-specific mortality in the population group with hypertension remains unresolved.

Methods:

We conducted a prospective cohort study using the data of 14 044 adults (age ≥18 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014, and followed this cohort until the end of December 2019. ePWV was calculated by using a regression equation for age and mean blood pressure (MBP), derived by the Arterial Stiffness Collaborative Group.

Results:

The weighted mean age of the 14 044 adults included was 54.79 years; 49.42% of all participants were men. During the median follow-up period of 11 years, 3795 deaths were recorded. In the fully adjusted cox regression model, each 1 m/s increase in ePWV was associated with an increased risk of 56% [hazard ratio 1.61; 95% confidence interval (CI) 1.49–1.64] risk for all-cause mortality. Every 1 m/s increase in ePWV resulted in an increased risk of mortality from cardiovascular disease, cerebrovascular disease, respiratory disease, Alzheimer's disease, accidents, cancer, influenza and pneumonia by 60, 70, 47, 118, 73, 41 and 103%, respectively. ePWV has a robust predictive value for 5- and 10-year all-cause mortality in the hypertensive population with AUCs of 0.749 and 0.741, respectively.

Conclusion:

Elevated ePWV is positively correlated with all-cause mortality and most cause-specific mortalities, independent of traditional risk factors. Moreover, ePWV demonstrates high accuracy in predicting 5-year and 10-year all-cause mortality, outperforming Framingham Risk Score.
IFN-γ deficiency in the rostral ventrolateral medulla contributes to stress-induced hypertension by impairing microglial synaptic engulfment
Authors: Tong Lei , Chen Gaojun , Liu Tianfeng , Wang Linping , Zhang Haili , Chen Fuxue , Zhang Shuai , Du Dongshu
Published: June 2023

Background:

Dysfunctional neurons and microglia in the rostral ventrolateral medulla (RVLM) have been implicated in the pathogenesis of stress-induced hypertension (SIH). Functional perturbation of microglial synaptic engulfment can induce aberrant brain circuit activity. IFN-γ is a pleiotropic cytokine that plays a role in regulating neuronal activity. However, existing research on the exploration of the effects of microglia on synapses in the RVLM is lacking, particularly on the function of IFN-γ in microglial synaptic engulfment involved in SIH.

Methods:

A SIH rat model was established by electric foot shocks combined with noise stimulation. The underlying mechanism of IFN-γ on synaptic density and microglial synaptic engulfment was investigated through in-vivo and in-vitro experiments involving gain of function, immunofluorescence, quantitative real-time PCR, western blot, and morphometric analysis. Furthermore, the function of IFN-γ in neuronal activity, renal sympathetic nerve activity (RSNA), and blood pressure (BP) regulation was determined through in-vivo and in-vitro experiments involving Ca2+ imaging, immunofluorescence, platinum–iridium electrode recording, ELISA, the femoral artery cannulation test, and the tail-cuff method.

Results:

The BP, heart rate, RSNA, plasma norepinephrine, and the number of c-Fos-positive neurons in SIH rats increased compared with those in control rats. Pre and postsynaptic densities in the RVLM also increased in SIH rats. IFN-γ and CCL2 expression levels were significantly reduced in the RVLM of the SIH group, whose microglia also exhibited an impaired capacity for synapse engulfment. IFN-γ elevation increased CCL2 expression and microglial synaptic engulfment and decreased synaptic density in vivo and in vitro. However, CCL2 inhibition reversed these effects. Moreover, the reduction of neuronal excitability, RSNA, plasma norepinephrine, and BP by IFN-γ was abrogated through CCL2 expression.

Conclusion:

IFN-γ deficiency in the RVLM impaired the microglial engulfment of synapses by inhibiting CCL2 expression and increasing synaptic density and neuronal excitability, thereby contributing to SIH progression. Targeting IFN-γ may be considered a potential strategy to combat SIH.
Neurogenic hypertension characterizes children with congenital central hypoventilation syndrome and is aggravated by alveolar hypoventilation during sleep
Authors: Dudoignon Benjamin , Bokov Plamen , Couque Nathalie , Denjoy Isabelle , Matrot Boris , Delclaux Christophe
Published: June 2023

Objectives:

Autonomic nervous system (ANS) dysfunction characterizes congenital central hypoventilation syndrome (CCHS). The objectives were to describe ambulatory blood pressure monitoring (ABPM) of children with CCHS, to assess cardiac ANS dysfunction as compared with control participants and to search for relationships between ANS dysfunction and blood pressure (BP) or night-time PCO2 measurements.

Methods:

Retrospective study of ABPM of children with CCHS and case (CCHS)–control (healthy children) study of heart rate variability (HRV) indices obtained during polysomnography (wakefulness, nonrapid eye movement sleep, rapid eye movement sleep, and whole night). The HRV indices analyzed were low, high-frequency powers, low frequency/high frequency, and for the whole night, SD1/SD2.

Results:

Twenty-four children with CCHS (14 girls) who underwent 81 ABPM (2–6/patient, 74 after 4 years) were included in the longitudinal study. Hypertension was evidenced in 29 of 45 (64%) ABPM made between 5 and 9 years of age as compared with 12 of 36 (33%) ABPM made between 10 and 17 years of age (P = 0.005). In the case–control study (12 pairs), as compared with control children, children with CCHS were characterized by a decreased HRV while awake, which was aggravated at night. In children with CCHS, at daytime, SBP percentiles positively correlated with low-frequency power (R = −0.82; P = 0.001), while at night-time, SBP percentiles negatively correlated with SD1/SD2 (R = −0.79; P = 0.010). The SD1/SD2 ratio also negatively correlated with median PCO2 under mechanical ventilation (R = −0.69; P = 0.013).

Conclusion:

Neurogenic hypertension is frequent in CCHS and correlates with ANS dysfunction, which also correlates with alveolar ventilation during mechanical ventilation.
Xpert MTB/RIF Assay for the Diagnosis of Pulmonary Tuberculosis Based on Bronchoalveolar Lavage Fluid: A Systematic Review and Meta-analysis
Authors: Chen Hao-Kai , Lin Chun-Xi , Lv Peng-Li , Li Wen-Feng , Feng Yu-Ying , Deng Xue-Jia , Xiao Jia-Qi , Guo Xu-Guang
Published: June 2023

Currently, tuberculosis (TB) is the second most lethal disease in the world caused by a single infectious pathogen. Rapid diagnosis of TB is of great importance for its treatment and management. Xpert MTB/RIF is a novel rapid diagnostic assay for the diagnosis of pulmonary TB (PTB). Use of the Xpert assay based on bronchoalveolar lavage fluid (BALF) samples is indicated when TB is suspected and sputum smears or cultures are negative. The aim of this meta-analysis was to systematically evaluate the diagnostic performance of the Xpert assay based on BALF samples for the diagnosis of PTB. A systematic review of previously published articles was performed, and relevant data were extracted. Meta-DiSc 1.4 and Stata 12.0 were used to analyze the data. WhenMycobacterium tuberculosiscultures were used as the criterion standard, the combined sensitivity of BALF-based Xpert was 0.89 (95% CI, 0.87–0.91), the specificity was 0.87 (95% CI, 0.85-0.88), the positive likelihood ratio was 8.28 (95% CI, 5.39–12.71), the negative likelihood ratio was 0.14 (95% CI, 0.10–0.19) and the diagnostic ratio was 84.08 (95% CI, 42.00–168.31). When composite reference standard was used as the criterion standard, the above observations were 0.69 (95% CI, 0.67–0.72), 0.98 (95% CI, 0.97–0.98), 41.40 (95% CI, 14.56–117.71), 0.28 (95% CI, 0.21–0.37) and 190.47 (95% CI, 50.56–717.54), respectively. The area under the summary receiver operating characteristic curve was close to 1 for both. Overall, the Xpert MTB/RIF assay based on BALF samples showed high sensitivity and specificity for the diagnosis of PTB and seems to be a reliable rapid detection method.
A case of fever in a returning traveler
Authors: Wrynn Alexander , Bhanot Nitin
Published: June 2023

After the lifting of COVID-19 restrictions, international travel has demonstrated recovery to prepandemic levels. Travel, particularly to tropical regions, can be associated with contracting various infectious diseases. For this reason, collecting a travel history is a necessity when assessing any patient with vague infectious symptoms, most notably fever. Early suspicion, identification, and treatment of tropical illnesses can be lifesaving. This case study concerns a patient who recently traveled to Africa and is under evaluation for fever in the emergency department. The proper approach to the febrile traveler and the pathophysiology, diagnosis, and treatment of malaria are reviewed.
Clinical trajectory of hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders in older adults
Authors: Anderson Linda K. , Lane Kari R.
Published: June 2023

Background:

Research on hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorder (hEDS/HSD) has described its natural history and clinical course in children, adolescents, and young to middle-aged adults. However, more research is needed on the clinical trajectory of hEDS/HSD into older age. Therefore, clinicians, including nurse practitioners, know little about identifying older adults with undiagnosed hEDS/HSD.

Objective:

This review sought to identify studies regarding aging in hEDS/HSD.

Data sources:

This scoping review included PubMed, Cumulative Index to Nursing and Allied Health Literature, and Scopus and found 15 studies that mentioned age or aging on the symptoms and health-related quality of life.

Conclusions:

No study had a stated aim regarding aging in hEDS/HSD, but all studies corroborated earlier natural history studies describing the age-related trajectory of manifestations in younger people. Studies found that symptom progression was heterogeneous, multisystemic, and unpredictable. Studies also noted prolonged diagnosis delays and long symptom duration, but the impact of these factors on outcomes was unclear. The high variability in patient outcomes precludes the prediction of outcomes based on the included studies. The clinical impact of aging on hEDS/HSD remains mostly speculative.

Implications for practice:

Nurse practitioners, especially those in primary care, should consider that older adults presenting with multimorbidity may have undiagnosed hEDS/HSD. More research is needed to identify symptom patterns and clinical history that may suggest an underlying connective tissue disorder.
Changes in chronic disease medications after admission to a Geriatric Health Services Facility: A multi-center prospective cohort study
Authors: Maruoka Hiroshi , Hamada Shota , Hattori Yukari , Arai Katsuaki , Arimitsu Kayoko , Higashihara Kazumi , Saotome Saiko , Kobayashi Asami , Watanabe Noriko , Kurata Naomi , Kishimoto Keiko , Kojima Taro
Published: June 2023

Older adults often receive polypharmacy, including some medications for chronic diseases. Nutritional management after admission to a nursing home may enable to deprescribe some chronic disease medications. This study aimed to investigate the status of deprescribing of chronic disease medications among nursing home residents, and to assess the appropriateness based on changes of laboratory test values and nutritional status. A multi-center prospective cohort study was conducted in 6 Geriatric Health Services Facilities, a major type of nursing homes in Japan. Newly admitted residents aged ≥ 65 years who took ≥1 medication for hypertension, diabetes, or dyslipidemia at admission were recruited. Participants who stayed for 3 months were included in the analysis. Medications at admission and 3 months after admission and situations for deprescribing were investigated. Changes in body mass index, blood pressure, laboratory tests (e.g., cholesterol and hemoglobin A1c levels), energy intake, and International Classification of Functioning, Disability and Health staging were evaluated. Sixty-nine participants (68% female, 62% aged ≥ 85 years) were included. At admission, 60 participants had medications for hypertension, 29 for dyslipidemia, and 13 for diabetes. Those receiving lipid-modifying drugs (mainly statins) decreased from 29 to 21 (72%; P = .008), since their cholesterol levels was within the normal range or was low at admission, and they had no history of cardiovascular events. However, there were no statistically significant changes in the frequencies of antihypertensive drugs (60 to 55; 92%; P = .063) or antidiabetic drugs (13 to 12; 92%; P = 1.000). During the 3-month observation, body mass index and diastolic blood pressure decreased, while energy intake and serum albumin level increased. Nutritional management after admission to a ROKEN may facilitate appropriate deprescribing of lipid-modifying drugs, by offseting the effects of discontinuation of these drugs.
Hsa_circ_0007401 regulates gemcitabine resistance of pancreatic cancer through the hsa-miR-6509-3p/fli1 axis
Authors: Han Chenchen , Zheng Huilin , Hu Die , Wang Maiqiu , Wang Hongpeng , Zhang Lei
Published: June 2023

Pancreatic cancer is a highly malignant cancer with a poor prognosis. Owing to the strong drug resistance of pancreatic cancer, adjuvant chemotherapy has failed to achieve good results in clinical practice. The expression profile data of circular RNA (circRNA) (GSE110580), microRNA (miRNA) (GSE79234), and messenger RNA (mRNA) (GSE140077, GES35141) were obtained from the gene expression omnibus database. The Cancer-Specific circRNA Database identified the structural pattern of circRNA, and the starBase and circBank databases together predicted the miRNA of circRNA. The mirDIP database predicts the target mRNAs of miRNAs and identifies the ceRNA network of circRNA-miRNA-mRNA via negative regulatory mechanisms. The final validation was performed using clinical data from the cancer treatment response gene signature database of patients treated with gemcitabine for pancreatic cancer of the cancer genome atlas. By differential expression analysis, 22 differential circRNAs (8 upregulated and 14 downregulated), 70 differential microRNAs (37 upregulated and 33 downregulated), and 256 differential messenger RNA (DEmRNA) (161 upregulated and 95 downregulated) were obtained. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses showed that DEmRNAs were associated with drug response, exogenous cellular stimulation, and the tumor necrosis factor signaling pathway. The screened downregulated differential circular RNA (hsa_circ_0007401), upregulated differential microRNA (hsa-miR-6509-3p), and downregulated DEmRNA (FLI1) were consistent with the negative regulation mechanism of the ceRNA network, and FLI1 was significantly downregulated in the data of gemcitabine-resistant pancreatic cancer patients in the cancer genome atlas (n = 26).
Mapping current status and emerging trends in NETosis: A bibliometric study
Authors: Wang Hongqin , Liu Xiaolin , Jia Zijun , Liu Li , Qi Yifei , Zhou Qingbing , Xu Fengqin , Zhang Ying
Published: June 2023

Background:

NETosis is a critical innate immune mechanism of neutrophils that contributes to the accelerated progression of autoimmune diseases, thrombosis, cancer, and coronavirus disease 2019 (COVID-19). This study qualitatively and quantitatively analyzed the relevant literature by bibliometric methods in order to provide a more comprehensive and objective view of the knowledge dynamics in the field.

Methods:

The literature on NETosis was downloaded from the Web of Science Core Collection, analyzed with VOSviewer, CiteSpace, and Microsoft for co-authorship, co-occurrence, and co-citation analysis.

Results:

In the field of NETosis, the United States was the most influential countries. Harvard University was the most active institutions. Mariana J. Kaplan and Brinkmann V were, respectively, the most prolific and most co-cited authors. Frontiers in Immunology, Journal of Immunology, Plos One, Blood, Science, Journal of Cell Biology, and Nature Medicine were the most influential journals. The top 15 keywords are associated with immunological and NETosis formation mechanisms. The keywords with the strongest burst detection were mainly related to COVID-19 (coronavirus, ACE2, SARS coronavirus, cytokine storm, pneumonia, neutrophil to lymphocyte ratio), and cancer (circulating tumor cell).

Conclusion:

Research on NETosis is currently booming. The mechanism of NETosis and its role in innate immunity, autoimmune diseases, especially systemic lupus erythematosus and rheumatoid arthritis, and thrombosis are the focus of research in the field of NETosis. A future study will concentrate on the function of NETosis in COVID-19 and recurrent metastasis of cancer.
Evaluation of dietary supplementation and/or herbal food consumption habits and common beliefs on their effectiveness during the COVID-19 pandemic
Authors: Kalkuz Şeyma , Göktaş Zeynep
Published: June 2023

Since 2020, COVID-19 has affected the entire world. Various dietary supplements/herbal foods are recommended to protect against and/or treat COVID-19 through social media and conventional media platforms, although their effects are unproven. Hence, this study aimed to investigate dietary supplementation and/or herbal food consumption habits intended to protect against and/or treat COVID-19, as well as common thoughts and beliefs about these products during the COVID-19 pandemic. This cross-sectional study was conducted as an online survey via the “SurveyMonkey” platform between June and December 2021. Participants were invited to participate in the study via social media (Instagram, Twitter, Facebook, WhatsApp) and the questionnaire was administered online. A total of 1767 participants were confirmed to be eligible. Overall, 35.3% used dietary supplements/herbal foods for protection against COVID-19 and 67.1% used them for treatment. Most believed that certain dietary supplements/herbal foods have an effect on the prevention and treatment of COVID-19. According to the COVID-19 infection status, participants differed in their opinions regarding the protective effects of vitamin D supplementation against COVID-19 (P = .02). It is important to raise public awareness of this issue and to avoid the unnecessary use of dietary supplements before sufficient evidence has been presented.