bluuebunny/crossref_metadata_2025 huggingface dataset:
EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy
Authors: Elitzur Sarah , Vora Ajay , Burkhardt Birgit , Inaba Hiroto , Attarbaschi Andishe , Baruchel Andre , Escherich Gabriele , Gibson Brenda , Liu Hsi-Che , Loh Mignon , Moorman Anthony V. , Möricke Anja , Pieters Rob , Uyttebroeck Anne , Baird Susan , Bartram Jack , Barzilai-Birenboim Shlomit , Batra Sandeep , Ben-Harosh Miriam , Bertrand Yves , Buitenkamp Trudy , Caldwell Kenneth , Drut Ricardo , Geerlinks Ashley V. , Gilad Gil , Grainger John , Haouy Stephanie , Heaney Nicholas , Huang Mary , Ingham Danielle , Krenova Zdenka , Kuhlen Michaela , Lehrnbecher Thomas , Manabe Atsushi , Niggli Felix , Paris Claudia , Revel-Vilk Shoshana , Rohrlich Pierre , Sinno Mohamad G. , Szczepanski Tomasz , Tamesberger Melanie , Warrier Rajasekharan , Wolfl Matthias , Nirel Ronit , Izraeli Shai , Borkhardt Arndt , Schmiegelow Kjeld
Published: November 2022

The development of a second malignancy after the diagnosis of childhood acute lymphoblastic leukemia (ALL) is a rare event. Certain second malignancies have been linked with specific elements of leukemia therapy, yet the etiology of most second neoplasms remains obscure and their optimal management strategies are unclear. This is a first comprehensive report of non-Hodgkin lymphomas (NHLs) following pediatric ALL therapy, excluding stem-cell transplantation. We analyzed data of patients who developed NHL following ALL diagnosis and were enrolled in 12 collaborative pediatric ALL trials between 1980-2018. Eighty-five patients developed NHL, with mature B-cell lymphoproliferations as the dominant subtype (56 of 85 cases). Forty-six of these 56 cases (82%) occurred during or within 6 months of maintenance therapy. The majority exhibited histopathological characteristics associated with immunodeficiency (65%), predominantly evidence of Epstein-Barr virus–driven lymphoproliferation. We investigated 66 cases of post-ALL immunodeficiency-associated lymphoid neoplasms, 52 from our study and 14 additional cases from a literature search. With a median follow-up of 4.9 years, the 5-year overall survival for the 66 patients with immunodeficiency-associated lymphoid neoplasms was 67.4% (95% confidence interval [CI], 56-81). Five-year cumulative risks of lymphoid neoplasm– and leukemia-related mortality were 20% (95% CI, 10.2-30) and 12.4% (95% CI, 2.7-22), respectively. Concurrent hemophagocytic lymphohistiocytosis was associated with increased mortality (hazard ratio, 7.32; 95% CI, 1.62-32.98; P = .01). A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.
Progressive multifocal leukoencephalopathy in patients treated with chimeric antigen receptor T cells
Authors: Goldman Adam , Raschi Emanuel , Chapman Joab , Santomasso Bianca D. , Pasquini Marcelo C. , Perales Miguel-Angel , Shouval Roni
Published: November 2022

Using 2 global postmarketing surveillance databases, Goldman and colleagues report that progressive multifocal leukoencephalopathy (PML), a viral disease associated with profound immunosuppression, occurs in approximately 0.9 cases per 1000 recipients of CD19-directed CAR T-cell therapy. The risk of PML appears higher with CAR T-cell therapy than other cancer therapies, but its precise role cannot be distinguished from antecedent therapies that these patients receive.
Efficacy of tixagevimab-cilgavimab in preventing SARS-CoV-2 for patients with B-cell malignancies
Authors: Davis James A. , Granger Katelynn , Roubal Kiera , Smith Deidra , Gaffney Kelly J. , McGann Mary , Cendagorta Alyssa , Thurlapati Aswani , Herbst Amanda , Hendrickson Lindsey , Hashmi Hamza , Hess Brian T.
Published: November 2022

COVID-19 still represents a major issue for patients with lymphoid malignancies, especially those on therapy, because of immune suppression and suboptimal responses to vaccination. Davis et al report on their experience with double dose tixagevimab-cilgavimab preexposure prophylaxis in a cohort of 251 patients with chronic lymphocytic leukemia, B-cell lymphomas, multiple myeloma, or B-cell acute lymphoblastic leukemia, 63% of whom had received 3 doses of the SARS-CoV-2 vaccine. Breakthrough infections within 3 months occur despite passive immunization, affecting 11% in this series; however, hospitalization rates are low, and mortality was avoided, suggesting benefit from this strategy.
Hypodiploidy has unfavorable impact on survival in pediatric acute myeloid leukemia: an I-BFM Study Group collaboration
Authors: Hammer Anne Sofie Borg , Juul-Dam Kristian Løvvik , Sandahl Julie Damgaard , Abrahamsson Jonas , Czogala Malgorzata , Delabesse Emmanuelle , Haltrich Iren , Jahnukainen Kirsi , Kolb E. Anders , Kovács Gábor , Leverger Guy , Locatelli Franco , Masetti Riccardo , Noren-Nyström Ulrika , Raimondi Susana C. , Rasche Mareike , Reinhardt Dirk , Taki Tomohiko , Tomizawa Daisuke , Zeller Bernward , Hasle Henrik , Kjeldsen Eigil
Published: November 2022

Hypodiploidy, defined as modal numbers (MNs) 45 or lower, has not been independently investigated in pediatric acute myeloid leukemia (AML) but is a well-described high-risk factor in pediatric acute lymphoblastic leukemia. We aimed to characterize and study the prognostic impact of hypodiploidy in pediatric AML. In this retrospective cohort study, we included children below 18 years of age with de novo AML and a hypodiploid karyotype diagnosed from 2000 to 2015 in 14 childhood AML groups from the International Berlin-Frankfurt-Münster (I-BFM) framework. Exclusion criteria comprised constitutional hypodiploidy, monosomy 7, composite karyotype, and t(8;21) with concurring sex chromosome loss. Hypodiploidy occurred in 81 patients (1.3%) with MNs, 45 (n = 66); 44 (n = 10) and 43 (n = 5). The most frequently lost chromosomes were chromosome 9 and sex chromosomes. Five-year event-free survival (EFS) and overall survival (OS) were 34% and 52%, respectively, for the hypodiploid cohort. Children with MN≤44 (n = 15) had inferior EFS (21%) and OS (33%) compared with children with MN = 45 (n = 66; EFS, 37%; OS, 56%). Adjusted hazard ratios (HRs) were 4.9 (P = .001) and 6.1 (P = .003). Monosomal karyotype or monosomy 9 had particular poor OS (43% and 15%, respectively). Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n = 18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5; P = .42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in the patients treated with SCT in CR1.
Waldenström macroglobulinemia whole genome reveals prolonged germinal center activity and late copy number aberrations
Authors: Maclachlan Kylee H. , Bagratuni Tina , Kastritis Efstathios , Ziccheddu Bachisio , Lu Sydney , Yellapantula Venkata , Famulare Chris , Argyropoulos Kimon , Derkach Andriy , Papaemmanuil Elli , Dogan Ahmet , Lesokhin Alexander , Usmani Saad Z. , Landgren C. Ola , Palomba Lia M. , Maura Francesco , Dimopoulos Meletios A.
Published: November 2022

The genomic landscape of Waldenström macroglobulinemia (WM) is characterized by somatic mutations in MYD88, present from the precursor stages. Using the comprehensive resolution of whole genome sequencing (WGS) in 14 CD19-selected primary WM samples; comparing clonal and subclonal mutations revealed that germinal center (GC) mutational signatures SBS9 (poly-eta) and SBS84 (AID) have sustained activity, suggesting that the interaction between WM and the GC continues over time. Expanding our cohort size with 33 targeted sequencing samples, we interrogated the WM copy number aberration (CNA) landscape and chronology. Of interest, CNA prevalence progressively increased in symptomatic WM and relapsed disease when compared with stable precursor stages, with stable precursors lacking genomic complexity. Two MYD88 wild-type WGS contained a clonal gain affecting chromosome 12, which is typically an early event in chronic lymphocytic leukemia. Molecular time analysis demonstrated that both chromosomal 12 gain events occurred early in cancer development whereas other CNA changes tend to occur later in the disease course and are often subclonal. In summary, WGS analysis in WM allows the demonstration of sustained GC activity over time and allows the reconstruction of the temporal evolution of specific genomic features. In addition, our data suggest that, although MYD88-mutations are central to WM clone establishment and can be observed in precursor disease, CNA may contribute to later phases, and may be used as a biomarker for progression risk from precursor conditions to symptomatic disease.
Excessive daytime sleepiness and fatigue in nonapnoeic snorers: improvement after UPPP
Authors: Janson C , Hillerdal G , Larsson L , Hultcrantz E , Lindholm CE , Bengtsson H , Hetta J
Published: November 2022

Even in the absence of sleep apnoea, heavy snoring may be a cause of excessive daytime sleepiness (EDS) and fatigue. The aim of this investigation was to study whether uvulopalatopharyngoplasty (UPPP) is effective in relieving snoring and excessive daytime sleepiness in nonapnoeic snoring patients. UPPP was assessed in 155 nonapnoeic, snoring patients (136 men and 19 women, mean age 45 yrs). Postoperative evaluation was made after 3 months in 105 patients, and after 12 months in 50 patients. Fifty four patients were evaluated after both 3 and 12 months. In 49 patients, a further evaluation was made after 2 yrs. The results were compared with those of 76 conservatively-treated, nonapnoeic, snoring patients, who were reinvestigated 12 months after their initial examination. The proportion of patients with frequent loud snoring had decreased postoperatively from 96 to 18%. A highly significant improvement was reported in EDS and daytime fatigue. The proportion of patients who reported problems staying awake when driving had decreased from 29 to 7%, and the number who felt rested when awakening in the morning had increased from 23 to 78 after the operation. The patients in the UPPP group had somewhat more severe symptoms before treatment than those treated conservatively. One year after treatment the situation had been reversed, with significantly more snoring and excessive daytime sleepiness in the conservatively-treated group. In conclusion, these results indicate that UPPP is effective in relieving snoring and EDS in nonapnoeic snorers.
Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep gas exchange in patients with chronic obstructive pulmonary disease (COPD)
Authors: Vos PJ , Folgering HT , de Boo TM , Lemmens WJ , van Herwaarden CL
Published: November 2022

The purpose of this study was to assess the short-term effects of chlormadinone acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake and asleep blood gas values. The study was conducted according to a randomized, double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic obstructive pulmonary disease. On the first two consecutive nights, all patients received either room air or oxygen, via a nasal cannula, in random order. They then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in identical capsules. On the third study night, after one week of drug treatment, the patients were tested breathing room air. CMA and ACET therapy decreased mean daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively, and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa, respectively. Supplemental oxygen caused increased CO2 retention during the day and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2) increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep oxygen saturation improved most with oxygen supplementation (7%), although ACET also caused significant improvement (4%). CMA administration had virtually no effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved subjective sleep quality. On CMA, minute ventilation increased in association with an augmentation of the hypercapnic ventilatory response. ACET treatment increased both hypercapnic and hypoxic ventilatory responses. We conclude from the group of patients with COPD studied, that the short-term effects of ACET treatment on gas exchange compare favourably with those of CMA. Oxygen therapy improves oxygenation slightly more than ACET, but aggravates CO2 retention.
Extrapolation of methacholine log-dose response curves with a Cumulative Gaussian Distribution function
Authors: Aerts JG , Bogaard JM , Overbeek SE , Verbraak AF , Thio P
Published: November 2022

Methacholine provocation tests are aimed at determining bronchial responsiveness. Recent investigations stress the importance of considering the entire log-dose response curve, yielding not only the provocative dose producing a 20% change in forced expiratory volume in one second (FEV1) (PC20), but also the plateau value and the steepest slope of the curve (reactivity). In three control subjects and seven patients with mild to moderate asthma, we have obtained methacholine log-dose response curves in which a plateau was reached. A new model, the Cumulative Gaussian Distribution (CGD) function was fitted to the whole curve. The upper part of the curve was also analysed with the Hofstee equation, which has been used in a number of other investigations and aimed at plateau estimation. The plateau values obtained by the fits were compared with the values actually measured (average response of last 3 points with a variation coefficient < 5% of the mean value) by using the coefficient of determination (R2) (Applied Statistics. Sachs). If all data points were considered, both fits yielded a plateau which slightly overestimated the measured plateau values. R2 for the CGD fit ranged from 0.93-0.99, indicating a highly significant correlation between actual and fitted data points. If the curves were truncated, such that the last four provocative doses were omitted from the analysis, the CGD fit still yielded plateau values; the mean difference from the measured plateaux, in % of the measured plateau values, was -2.6% (SD 18.2). In only three out of the 10 cases did the Hofstee equation yield plateau values with a deviation from 'measured' < 47% of the measured value.(ABSTRACT TRUNCATED AT 250 WORDS)
Relaxant effects and durations of action of formoterol and salmeterol on the isolated human bronchus
Authors: Naline E , Zhang Y , Qian Y , Mairon N , Anderson GP , Grandordy B , Advenier C
Published: November 2022

The objective of this study was to evaluate the potency and efficacy (intrinsic activity) of formoterol and salmeterol and their duration of action in comparison with other beta-adrenoceptor agonists in isolated human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Potency (-log of the concentration of drug inducing 50% of maximal relaxation (-log EC50)) and efficacy (maximal effect (Emax), % of response to theophylline 3 x 10(-3) mol.l-1) were determined by analysis of cumulative isometric concentration-response curves to beta 2-adrenoceptor agonists in bronchial rings at resting tone or contracted maximally with acetylcholine 10(-3) mol.l-1 to induce functional antagonism. The onset and duration of action of beta-adrenoceptor agonists were measured by assessing the relaxant activity of drugs on the basal tone of isolated bronchi. In terms of potency, the rank order of the substances studied was formoterol > fenoterol > or = salmeterol > or = isoprenaline > or = salbutamol > or = adrenaline > or = terbutaline. Formoterol was 150-200 times more potent than isoprenaline. On preparations contracted with acetylcholine 10(-3) mol.l-1 the intrinsic activity (IA) of salbutamol, terbutaline and salmeterol compared with that of isoprenaline ranged 0.62-0.66. Intrinsic activity was higher with formoterol (0.84) and fenoterol (0.75). The onset of action of formoterol (2.14 +/- 0.55 min, n = 11) was not significantly different from that of salbutamol (1.90 +/- 0.24 min, n = 8) but shorter than that of salmeterol (6.40 +/- 1.40 min, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
Serum eosinophilic cationic protein and lactoferrin related to smoking history and lung function
Authors: Jensen EJ , Pedersen B , Schmidt E , Venge P , Dahl R
Published: November 2022

Some smokers have an accelerated loss of lung function, possibly due to a chronic bronchial inflammation in which granulocytes are involved. Eosinophil cationic protein (ECP) and lactoferrin (LF) are granule proteins in the eosinophil and neutrophil granulocyte, respectively. We wanted to investigate the relationship of serum (s) ECP and LF concentrations to smoking history and lung function alteration. This partly cross-sectional and partly prospective study included 98 nonatopic smokers and 31 lifetime nonsmokers. As participants in a smoking cessation programme, 50 of the 98 smokers ceased smoking for > or = 1 year. Smoking history, lung function and blood samples were obtained at the start of the study, and smokers and ex-smokers also gave blood samples 3, 6 and 12 months later. s-ECP and s-LF were elevated in smokers compared to people who had never smoked. s-ECP was linearly associated with daily cigarette consumption and forced expiratory volume in one second (FEV1) residuals. In a multiple linear regression analysis, low s-ECP and high s-LF were associated with decreased FEV1 residuals. s-ECP and s-LF together accounted for 10.2% of the variation in FEV1 residuals. After smoking cessation, s-ECP and s-LF decreased within 6 months. s-ECP and s-LF are raised in smokers, and may serve as indicators of granulocyte activation. We speculate that they might contribute to prediction of accelerated lung function loss in smokers, but this question needs further investigation in a prospective study.
Different bronchodilating effect of salmeterol and formoterol in an adult asthmatic
Authors: Ulrik CS , Kok-Jensen A
Published: November 2022

New long-acting beta 2-adrenoceptor agonists, salmeterol and formoterol, have recently been marketed for treatment of asthma, but studies comparing the clinical efficacy of the two drugs have not been published. We report on an asthmatic patient who had a striking difference in bronchodilating effect of the two drugs, formoterol being more effective than salmeterol both in immediate response and during long-term treatment. Although, both formoterol and salmeterol are highly selective for the beta 2-adrenoceptors (comparable to salbutamol and terbutaline), differences in their chemical structure suggest differences in their mechanisms of action or receptor specificity. The clinical implication of our observation appears to be that a less favourable response in an individual patient to one of the long-acting beta 2-agonists should not preclude a trial with another. Future studies comparing the clinical efficacy of formoterol and salmeterol should probably also address the question of responders and nonresponders to these drugs; and furthermore, seek to explore a possible relationship to inherited variance in beta 2-receptors.
Coexisting subdural and intercostal haemangiomata
Authors: Aguilo R , Montesinos C , Llobera M
Published: November 2022

Haemangioma in the chest wall is a very rare entity, seldom described in the literature. We report the case of a 23 year old woman presenting with independent, cervical subdural and intercostal haemangiomata. She suffered several episodes of recurrent, self-limiting subdural haemorrhage before diagnosis was made by magnetic nuclear resonance, aortography and selective intercostal angiography. Surgical excision was performed in both locations with excellent results.
Respiratory symptoms and airway responsiveness in apparently healthy workers exposed to flour dust
Authors: Bohadana AB , Massin N , Wild P , Kolopp MN , Toamain JP
Published: November 2022

Our aim was to measure the levels of exposure to wheat flour dust in a modern industrial bakery, and to assess the relationship between respiratory symptoms, sensitization to wheat flour antigens and airway responsiveness in the workforce. Forty four flour-exposed male workers and 164 unexposed controls were examined. Inspirable dust concentrations were measured using personal samplers. Respiratory symptoms were assessed by questionnaire, sensitization to wheat flour antigens by skin-prick tests, and methacholine airway challenge (MAC) test using an abbreviated method. Subjects were labelled MAC+ if forced expiratory volume in one second (FEV1) fell by 20% or more. The linear dose-response slope (DRS) was calculated as the percentage fall in FEV1 at last dose divided by the total dose administered. Inspirable dust concentrations were within acceptable limits in all working areas but one. The proportion of subjects with one or more symptoms and with airway hyperresponsiveness was significantly greater among flour-exposed workers than among controls. Using logistic or linear regression analysis, airway responsiveness was found to be strongly related to working at the bakery and to the baseline level of lung function. A positive skin-prick test was found in only 11% of flour-exposed workers and 6% of controls. In conclusion, our data show that despite exposure to relatively low concentration levels of inspirable flour dust, subjects working in the baking industry are at risk of developing both respiratory symptoms and airway hyperresponsiveness.
Autonomic nerve dysfunction in COPD as assessed by the acetylcholine sweat-spot test
Authors: Stewart AG , Marsh F , Waterhouse JC , Howard P
Published: November 2022

Patients with hypoxic chronic obstructive pulmonary disease (COPD) have evidence of a subclinical parasympathetic autonomic neuropathy, with apparent preservation of sympathetic function. However, these cardiovascular-respiratory tests might have been biased by concomitant chest disease, the acetylcholine sweat-spot test avoids this bias. This sweat-spot test assesses sympathetic nerve function, it relies upon the fact that denervated sweat glands do not produce sweat. 35 patients with hypoxaemic COPD and seven age matched normal subjects were studied. Following intradermal injection of 0.1 of 1% acetylcholine into the dorsum of the feet, the number of sweatglands able to respond in a given surface area was recorded. Cardiovascular autonomic nerve function, arterial oxygen and carbon dioxide tensions, lung function and cigarette consumption were also recorded. The acetylcholine sweat-spot test was highly repeatable in eight COPD patients, no person with normal or frankly abnormal function being wrongly assigned. The age matched control subjects had normal acetylcholine sweat-spot scores and cardiovascular autonomic tests. The acetylcholine sweat-spot test was abnormal in 24 patients, borderline in 8 and normal in 3 patients. The abnormal sweat-spot test group had significant worse FEV1, arterial blood gases and autonomic function. The acetylcholine sweat-spot score correlated with the severity of arterial hypoxaemia (r = 0.78, p < 0.001) and with the parasympathetic cardiovascular tests (r = 0.80, p < 0.001). In conclusion, patients with hypoxaemic COPD have a parasympathetic cardiovascular and a peripheral sympathetic autonomic neuropathy. The acetylcholine sweat-spot test is repeatable, easy to perform and a sensitive indicator for autonomic dysfunction in breathless individuals with COPD.
Airways obstruction and two year survival in patients with severe alpha 1-antitrypsin deficiency
Authors: Seersholm N , Dirksen A , Kok-Jensen A
Published: November 2022

Because of the limited number of donor organs available, the selection of patients for lung transplantation is crucial. One important issue in setting priorities is the life expectancy without transplantation. The purpose of this study was to estimate survival based on lung function, in alpha 1-antitrypsin deficient patients. Data from the Danish alpha 1-antitrypsin deficiency registry were analysed. The basic element of the analysis was two year intervals, characterized by date of spirometry and known mortality status 2 yrs later. We found a simple exponential relationship between lung function (forced expiratory volume one second (FEV1)) and two year survival on conservative treatment. The formula implies an almost 100% two year survival until FEV1 falls below one third of predicted normal; at this level two year mortality increases and will reach 50% at a FEV1 of 15% predicted. In conclusion, the two year mortality of emphysema patients due to alpha 1-antitrypsin deficiency increases exponentially with decreasing FEV1 and the results imply that only a few patients who underwent lung transplantation would have had a better two year prognosis without this procedure.
Salmeterol-induced vertigo
Authors: Lopez-Guillen A , Marques L , Lopez-Llorente MT , Pastor E , Figueras A
Published: November 2022

Dizziness, together with hypotension and faintness, are well-known adverse drug reactions of salbutamol that have been related to its cardiovascular effects. However, we could find no published reference to vertigo in patients taking salmeterol, in the absence of cardiovascular alterations. We present the case of a woman who experienced four independent episodes of vertigo lasting 36 h each, following four inhalations of salmeterol several months apart. The close temporal relationship between the inhalation of salmeterol and the onset of symptoms, as well as the positive re-exposures, reinforce this alleged association.
TADMaster: a comprehensive web-based tool for the analysis of topologically associated domains
Authors: Higgins Sean , Akpokiro Victor , Westcott Allen , Oluwadare Oluwatosin
Published: November 2022

Background

Chromosome conformation capture and its derivatives have provided substantial genetic data for understanding how chromatin self-organizes. These techniques have identified regions of high intrasequence interactions called topologically associated domains (TADs). TADs are structural and functional units that shape chromosomes and influence genomic expression. Many of these domains differ across cell development and can be impacted by diseases. Thus, analysis of the identified domains can provide insight into genome regulation. Hence, there are many approaches to identifying such domains across many cell lines. Despite the availability of multiple tools for TAD detection, TAD callers' speed, flexibility, result inconsistency, and reproducibility remain challenges in this research area.

Results

In this work, we developed a computational webserver called TADMaster that provides an analysis suite to directly evaluate the concordance level and robustness of two or more TAD data on any given genome region. The suite provides multiple visual and quantitative metrics to compare the identified domains' number, size, and various comparisons of shared domains, domain boundaries, and domain overlap.

Conclusions

TADMaster is an efficient and easy-to-use web application that provides a set of consensus and unique TADs to inform the choice of TADs. It can be accessed at http://tadmaster.io and is also available as a containerized application that can be deployed and run locally on any platform or operating system.
Effect of grazing disturbance on floral display, pollen limitation and plant pollination efficiency in the desert steppe
Authors: Chen Min , Zhao Xue-Yong , Yue Ping , Guo Xin-Xin , Qiao Jing-Juan , Li Xiang-Yun
Published: November 2022

Background

Grazing disturbance usually affects floral display and pollination efficiency in the desert steppe, which may cause pollen limitation in insect-pollinated plants. Effective pollination is essential for the reproductive success of insect-pollinated plants and insufficient pollen transfer may result in pollen limitation. Caragana microphylla Lam is an arid region shrub with ecological importance. Few studies have been conducted on how grazing disturbance influences pollen limitation and pollination efficiency of C. microphylla. Here, we quantify the effect of different grazing intensities on floral display, pollinator visitation frequency and seed production in the Urat desert steppe.

Results

In C. microphylla, supplemental hand pollination increased the seed set, and pollen limitation was the predominant limiting factor. As the heavy grazing significantly reduced the seed set in plants that underwent open-pollination, but there was no significant difference in the seed set between plants in the control plots and plants in the moderate grazing plots. Furthermore, there was a higher pollinator visitation frequency in plants in the control plots than in plants in the heavy grazing plots.

Conclusions

We found that pollinator visitation frequency was significantly associated with the number of open flowers. Our findings also demonstrated that seed production is associated with pollinator visitation frequency, as indicated by increased seed production in flowers with higher pollinator visitation frequency. Therefore, this study provides insight into the effect of different grazing intensities on floral display that are important for influencing pollinator visitation frequency and pollination efficiency in desert steppes.
Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda
Authors: Baluku Joseph Baruch , Nabwana Martin , Nalunjogi Joanitah , Muttamba Winters , Mubangizi Ivan , Nakiyingi Lydia , Ssengooba Willy , Olum Ronald , Bongomin Felix , Andia-Biraro Irene , Worodria William
Published: November 2022

Background

Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda.

Methods

In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity.

Results

Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4–69.1), hypertension (40.6%; 33.8–47.9), central obesity (39.3%; 32.9–46.1), smoking (36.3%; 30.1–43.1), high BMI (8.0%; 5.0–12.8) and DM (6.5%; 3.7–11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06–1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14–3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21–0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00–1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00–1.06).

Conclusion

There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.
Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis
Authors: Itagaki Yuki , Hayakawa Mineji , Maekawa Kunihiko , Kodate Akira , Moriki Koyo , Takahashi Yuki , Sageshima Hisako
Published: November 2022

Background

A shortage of donor organs amid high demand for transplantable organs is a worldwide problem, and an increase in organ donation would be welcomed by the global healthcare system. Patients with brain death (BD) are potential organ donors, and early prediction of patients with BD may facilitate the process of organ procurement. Therefore, we developed a model for the early prediction of BD in patients who survived the initial phase of out-of-hospital cardiac arrest (OHCA).

Methods

We retrospectively analyzed data of patients aged < 80 years who experienced OHCA with a return of spontaneous circulation (ROSC) and were admitted to our hospital between 2006 and 2018. We categorized patients into either a non-BD or BD group. Demographic and laboratory data on ED admission were used for stepwise logistic regression analysis. Prediction scores of BD after OHCA were based on β-coefficients of prognostic factors identified in the multivariable logistic model.

Results

Overall, 419 OHCA patients with ROSC were admitted to our hospital during the study period. Seventy-seven patients showed BD (18.3%). Age and etiology of OHCA were significantly different between the groups. Logistic regression analysis confirmed that age, low-flow time, pH, and etiology were independent predictors of BD. The area under the receiver operating characteristic curve for this model was 0.831 (95% confidence interval, 0.786–0.876).

Conclusions

We developed and internally validated a new prediction model for BD after OHCA, which could aid in the early identification of potential organ donors for early donor organ procurement.
Association of renal function screening frequency with renal function decline in patients with type 2 diabetes: a real-world study in primary health care
Authors: Sundqvist Henry , Heikkala Eveliina , Jokelainen Jari , Russo Giuseppina , Mikkola Ilona , Hagnäs Maria
Published: November 2022

Aims

To examine the association of the screening frequency of estimated glomerular filtration rate (eGFR) with the substantial reduction in eGFR (≥ 25%) among type 2 diabetes (T2D) patients with normal (eGFR≥60 ml/min/1.73 m2) and impaired kidney function (eGFR< 60 ml/min/1.73 m2).

Methods

A longitudinal study involving 5104 T2D patients with follow-up period of 6.8 years (1.9 SD) were treated at the Rovaniemi Health Center, Rovaniemi, Finland during 2011–2019. The association between the screening frequency of eGFR (yearly vs. non-yearly) and the substantial reduction in eGFR was studied with logistical models and adjusted with biochemical variables and preventive medications.

Results

Among the T2D patients with normal kidney function, non-yearly eGFR screening was significantly associated with substantial eGFR reduction in both unadjusted (odds ratio [OR] 3.29, 95% confidence interval [CI] 2.54–4.33) and adjusted models (OR 2.06, 95% CI 1.21–3.73) compared with yearly screening frequency. In the group of patients with impaired kidney function in the unadjusted model, non-yearly eGFR screening was significantly associated with substantial eGFR reduction (OR 2.38, 95% CI 1.30–4.73), but became non-significant after adjustments (OR 1.89, 95% CI 0.61–7.21).

Conclusions

This study underscores the role of regular eGFR screening in the prevention of kidney function decline.
Spontaneous ischemic neuropathy of the sciatic nerve due to arterial occlusion – a rare cause of acute neuropathy not to be missed, a report of two cases
Authors: Dietmann Anelia , von Martial Rascha , Scheidegger Olivier
Published: November 2022

Background

Ischemic neuropathy of the sciatic nerve without preceding vascular surgical procedures is a rare condition and may be due to arterial occlusion in one limb.

Case presentations

We present two cases with acute onset of pain and sensory symptoms such as pins and needles and numbness in the foot with no or mild motor symptoms. In the neurological work-up, electrophysiological signs of axonal neuropathy of both peroneal and tibial nerves were demonstrated and T2 hyperintensity was seen in the distal sciatic nerves on MR neurography as well as signs indicating arterial thrombosis in the corresponding vessels. Recanalization was obtained in both patients angiographically with significant improvement in one patient.

Conclusions

Spontaneous arterial occlusion of major or peripheral arteries is a rare but important cause of acute onset of single or multiple axonal mononeuropathies of one extremity. Recognition of this infrequent cause is essential since it requires immediate and specific therapeutic options.
Application of chromosome microarray analysis and karyotyping in diagnostic assessment of abnormal Down syndrome screening results
Authors: Kang Han , Wang Lingxi , Li Xingyu , Gao Chonglan , Xie Yamei , Hu Yu
Published: November 2022

Background

Down syndrome (DS) is the most common congenital cause of intellectual disability and also leads to numerous metabolic and structural problems. This study aims to explore the application value of chromosomal microarray analysis (CMA) and karyotyping in prenatal diagnosis for pregnant women with abnormal DS screening results.

Methods

The study recruited 1452 pregnant women with abnormal DS screening results including 493 with an enlarged nuchal translucency thickness (NT ≥ 2.5 mm) and 959 with an abnormal second-trimester maternal serum biomarker screening results. They underwent amniocentesis to obtain amniotic fluid for CMA and karyotyping.

Results

CMA identified 74/1452 abnormal results, which was more efficient than karyotyping (51/1452, P < 0.05.) CMA is equivalent to traditional karyotyping for identifying aneuploidies. Compared to karyotyping CMA identified 1.90% more copy number variants (CNVs) ranging from 159Kb to 6496Kb. However, 34.4% of them were recurrent pathogenic CNVs associated with risk of neurodevelopmental disorders. CMA identified 13 variants of uncertain significance (VUS) results and 1 maternal uniparental disomy (UPD) of chromosome 7. Karyotyping identified 3 mosaic sex chromosome aneuploidy and 4 balanced translocation which could not be identified by CMA. In enlarged NT group, karyotyping identified 80.9% abnormal results while in serum screening group karyotyping identified 35.7%. However, the incidence of pathogenic/likely pathogenic (P/LP) CNVs was nearly the same in both groups. That was because aneuploidies and gross duplication/deletion were previously screened out by NT scan.

Conclusions

CMA and karyotyping have both advantages and disadvantages in prenatal diagnosis of pregnant women with abnormal DS screening results. However, there was not enough evidence to support routine CMA in pregnant women with abnormal DS screening results.
Micturition in the toilet compared with bedpan in laboring Nulliparas: a randomized controlled trial
Authors: Kamarudin Maherah , Chong Wen Kiat , Hamdan Mukhri , Adlan Aizura Syafinaz , Saaid Rahmah , Tan Peng Chiong
Published: November 2022

Background

Bladder overdistension in labor may lead to prolonged postpartum urinary retention. We hypothesized that nulliparas mobilizing to toilet is more likely to achieve satisfactory micturition.

Methods

One hundred sixteen (58 in each arm) term nulliparas in labor with filled bladders were randomized to mobilizing to the toilet or using bedpan to micturate. Primary outcome was satisfactory micturition defined as ultrasound derived post-void bladder volume < 150 ml. Following unsatisfactory micturition, participants crossover to the opposed intervention. Participants were catheterized if after crossover, residual bladder volume was ≥250 ml.

Results

Satisfactory micturition rates were 55/58 (95%) vs. 43/58 (74%) RR 1.28 95%CI 1.08–1.51 NNTb 4.8 95%CI 3.0–12.4 P = 0.008, failure to micturate 1/58 (2%) vs. 8/58 (14%) RR 0.13 95%CI 0.02–0.97 NNTb 8.3 95%CI 4.6–38.7 P = 0.047. After cross over following unsatisfactory bladder voiding, satisfactory micturition rates were 0/3 (0%) vs 13/15 (87%) P = 0.024, bladder catheterization rates were 3/58 (5%) vs. 2/58 (4%) RR 95%CI 1.5 (0.26–8.65) P = 0.648, maternal satisfaction with allocated intervention 55/58 (95%) vs. 9/58 (16%) RR 95%CI 6.1 (3.3–11.2) NNTb 95%CI 1.3 (1.1–1.5) P <  0.0001 and preference for mobilizing to the toilet if micturition was needed again during labor 55/58 (95%) vs. 53/58 (92%) for mobilizing to the toilet compared to bedpan use arms respectively. Labor and neonatal outcomes were similar.

Conclusion

Satisfactory micturition was more frequently achieved with mobilization to the toilet than bedpan use. Women in both arms overwhelmingly prefer to mobilize to the toilet to urinate.

Trial registration

This study was registered with ISRCTN on 17/07/2019 with trial identification number: ISRCTN17787339. First participant was recruited on 31/07/2019. The last patient was recruited on 18/12/2019.
M7G-Related lncRNAs predict prognosis and regulate the immune microenvironment in lung squamous cell carcinoma
Authors: Pan Junfan , Huang Zhidong , Lin Hancui , Cheng Wenfang , Lai Jinhuo , Li Jiancheng
Published: November 2022

Background

N7-Methylguanosine (m7G) and long non-coding RNAs (lncRNAs) have been widely studied in cancer and have been found to be useful for assessing tumor progression. However, the role of m7G-related lncRNAs in lung squamous cell carcinoma (LUSC) remains unclear. Thus, it is crucial to identify m7G-associated lncRNAs with definitive prognostic value. This study aimed to investigate the prognostic value, correlation with tumor mutation burden, and impact on the tumor immune microenvironment of m7G-related lncRNAs in LUSC. 

Methods

LUSC transcriptome data and clinical data were downloaded from The Cancer Genome Atlas, and an m7G-related lncRNA-mRNA co-expression network was constructed using Pearson’s correlation analysis. Cox regression analyses were used to determine a risk model for m7G-associated lncRNAs with prognostic value. The risk signature was verified using the Kaplan–Meier method, receiver operating characteristic curve analysis, and principal component analysis. A nomogram based on risk scores and clinical characteristics was then developed. Gene set enrichment analysis was used for functional annotation to analyze the risk signature. The association among the risk signature, tumor mutational burden, and tumor-infiltrating immune cells was then analyzed. RT-qPCR was used to investigate the expression of 6 m7G-related lncRNAs in LUSC cells. The cytological function of SRP14-AS1 was verified by wound-healing assay and transwell assay.

Results

A total of 293 m7G-related lncRNAs were identifed, 27 candidate m7G-related lncRNAs were signifcantly associated with overall survival (OS). Six of these lncRNAs (CYP4F26P, LINC02178, MIR22HG, SRP14-AS1, TMEM99, PTCSC2) were selected for establishment of the risk model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p < 0.001). Multivariate cox regression analysis indicated that the model could be an independent prognostic factor for LUSC (HR = 1.859; 95% CI 1.452–2.380, p < 0.001). The ROC curve analysis revealed that the AUCs for OS in the 3-, and 5-year were 0.682, 0.657, respectively. GSEA analysis revealed that the risk model was closely related to immune-related pathways. Compared with normal lung epithelial cells, four m7G-related lncRNAs were higher expressed in cancer cells and two were lower expressed, among which knockdown of SRP14-AS1 promoted the proliferation and migration of LUSC cells.

Conclusion

A risk model based on six m7G-related lncRNAs with prognostic value may be a promising prognostic tool in LUSC and guide individualized patient treatment.
Point-of-care C-reactive protein test results in acute infections in children in primary care: an observational study
Authors: De Rop Liselore , De Burghgraeve Tine , De Sutter An , Buntinx Frank , Verbakel Jan Y
Published: November 2022

Background

Acute infections are a common reason for children to consult primary care. Serious infections are rare but differentiating them from self-limiting illnesses remains challenging. This can lead to inappropriate antibiotic prescribing. Point-of-care C-reactive protein testing is used to guide antibiotic prescribing in adults. However, in children its use remains unclear. The purpose of this study was to assess point-of-care CRP test levels with respect to patients’ characteristics, care setting, preliminary diagnosis, and management.

Methods

A prospective observational study was performed in children with an acute infection presenting to ambulatory care in Belgium.

Results

In this study 8280 cases were analysed, of which 6552 had a point-of-care CRP value available. A total of 276 physicians participated. The median patient age was 1.98 years (IQR 0.97 to 4.17), 37% of children presented to a general practitioner, 33% to a paediatric out-patient clinic, and 30% to the emergency department. A total of 131 different preliminary diagnoses were found, with acute upper airway infection as the most frequent. In 6% (n = 513) patients were diagnosed with a serious infection. The most common serious infection was pneumonia. Antibiotics were prescribed in 28% (n = 2030) of all episodes. The median CRP over all infectious episodes was 10 mg/L (IQR < 5–29). Children below 5 years of age and those presenting to a paediatrician had a higher median CRP. Median CRP in patients with serious infections was 21 mg/L (IQR 6 to 63.5). Pneumonia had a median CRP of 48 mg/L (IQR 13–113). In the episodes with antibiotics prescription, median CRP level was 29 mg/L (IQR 10–58) compared to 7 mg/L (IQR < 5–19) when they were not prescribed.

Conclusion

A low POC CRP as a standalone tool did not seem to be sufficient to rule out serious infections, but its potential in assessing serious infections could increase when integrated in a clinical decision rule.

Trial registration

ClinicalTrials.gov Identifier: NCT02024282 (registered on 31/12/2013).
Association between serum vitamin D levels and visceral adipose tissue among adolescents: a cross-sectional observational study in NHANES 2011–2015
Authors: Li Yan-feng , Zheng Xiao , Gao Wen-lan , Tao Feng , Chen Yi
Published: November 2022

Background

In recent years, obesity and vitamin D deficiency are more prevalent among adolescents. Improving our knowledge of the link between vitamin D and visceral adipose tissue (VAT) is essential for the health of adolescents. This study aimed to examine the connection between serum vitamin D levels and VAT mass among adolescents participating in the United States.

Methods

This is a cross-sectional study that used data from the 2011 to 2015 National Health and Nutrition Examination Survey (NHANES). The connection between serum vitamin D levels and VAT was investigated using weighted multiple linear regression models. Potential nonlinear relationships were explored using smooth curve fitting.

Results

The analysis included 3171 adolescents aged 12–19 years. Vitamin D levels were shown to be inversely linked with VAT in the full-adjusted model (β = − 0.34, 95% CI: − 0.49 to − 0.19). When stratified analyses by gender, this negative relationship persisted in the girls’ group (β = − 0.39, 95% CI: − 0.60 to − 0.19), but not in the boys’ group (β = − 0.06, 95% CI: − 0.25 to 0.13). When stratified analysis by race, this negative relationship persisted in the Mexican American group (β = − 0.61, 95% CI: − 1.03 to − 0.19), and the non-Hispanic White group (β = − 0.27, 95% CI: − 0.54 to − 0.01), but not in the other groups.

Conclusions

Our findings confirmed that serum vitamin D levels negatively correlated with VAT among adolescents in the United State, especially in girls, the Mexican American and non-Hispanic White. Further research is needed to determine whether increasing serum vitamin D levels decrease VAT among adolescents.