bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway goblet cells: responsive and adaptable front-line defenders
Authors: Rogers DF
Published: November 2022

Goblet cells are situated in the epithelium of the conducting airways, often with their apical surfaces protruding into the lumen, a location which fits them for a rapid response to inhaled airway insults. Together with the submucosal glands, goblet cells secrete high molecular weight mucus glycoproteins (mucins), which confer upon the airway surface fluid the requisite biochemical and biophysical properties which determine the efficiency of entrapment and transportation of inhaled irritants, particles and micro-organisms. The diversity of glycosylation of airway mucins may be important in facilitating adherence of micro-organisms to mucus prior to mucociliary clearance. Other secretory products, including lipids and "small" glycoproteins, may also be produced by goblet cells. It is possible that goblet cells have the potential to produce markedly more mucus than do the glands. Mucins are tightly packed in the intracellular granules of the goblet cell. The morphology of these granules varies with fixation technique, and release of mucins may be via a combination of merocrine and apocrine secretion. Discharge of mucus is accomplished remarkably rapidly (tens of milliseconds) and vast quantities of mucus are released (size expansions from the granule of many hundredfold). Depending upon species and preparation, goblet cells discharge mucus in response to a wide variety of stimuli, including proteinases, irritant gases, inflammatory mediators, reactive oxygen species, nerve activation and changes in the biophysical environment. Under normal conditions, goblet cell proliferation and differentiation, particularly to ciliated cells, contributes to maintenance of the airway epithelial cell population. In addition to participating in acute airway defence, goblet cells increase in number in response to chronic airway insult, with a resultant increase in output of mucus. The increase in number of cells is via hyperplastic and metaplastic mechanisms. Early triggers for the development of a hypersecretory epithelium include excessive discharge of mucus and increased expression of airway mucin messenger ribonucleic acid (mRNA). Cessation of chronic airway stress rapidly reverses the increased number of goblet cells. Irritant-induced increases in number of goblet cells can be inhibited by a variety of drugs with anti-inflammatory and mucoregulatory properties, and the reversal to normal numbers after cessation of the irritation is speeded by these drugs. The ability of goblet cells to be progenitors of ciliated cells, to rapidly produce vast quantities of mucus in response to acute airway insult, and to change in number according to variations in chronic insult indicates that these cells are vitally important responsive and adaptable front-line defenders of the airways.
Pseudomonas-induced neutrophil recruitment in the dog airway in vivo is mediated in part by IL-8 and inhibited by a leumedin
Authors: Jorens PG , Richman-Eisenstat JB , Housset BP , Massion PP , Ueki I , Nadel JA
Published: November 2022

A bacteria-free supernatant of Pseudomonas aeruginosa induces the production of neutrophil chemotactic activity in human bronchial epithelial cells in vitro that is due to the potent chemotactic factor, interleukin-8 (IL-8). Because P. aeruginosa supernatant itself is not chemotactic, we hypothesized that intratracheal P. aeruginosa induces the production of neutrophil chemotactic factors, including IL-8, in vivo. Because neutrophils play a key role in cystic fibrosis, inhibition of neutrophil recruitment might be therapeutic. We studied the effect of P. aeruginosa supernatant in the isolated tracheal segment of dogs in vivo, and we measured neutrophil chemotactic activity in vitro in the tracheal fluid. We also determined the local effect of intratracheal administration of leumedin NPC 15669, an inhibitor of neutrophil recruitment, on IL-8- and Pseudomonas-induced neutrophil accumulation. P. aeruginosa supernatant and IL-8 both caused time-dependent accumulation of neutrophils in the tracheal fluid. Tracheal fluid obtained after P. aeruginosa administration had neutrophil chemotactic activity in vitro that was significantly inhibited by the IL-8 antibody. Intratracheal NPC 15669 prevented both IL-8- and Pseudomonas-induced accumulation of neutrophils. We conclude that P. aeruginosa supernatant recruits neutrophils into the airway indirectly by inducing the production of chemotactic factors, including IL-8. Our results suggest a potential therapeutic role for leumedins in chronic airway diseases.
Increased type I procollagen mRNA transcripts in the lungs of mice during the development of bleomycin-induced fibrosis
Authors: Shahzeidi S , Jeffery PK , Laurent GJ , McAnulty RJ
Published: November 2022

In this study, in situ hybridization has been used to investigate the localization of type I procollagen messenger ribonucleic acid (mRNA) in normal lung, and in the lungs of mice during the development of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced by a single intratracheal instillation of bleomycin sulphate (6 mg.kg-1 body weight), and tissues examined at times up to 35 days thereafter. Tissue transcripts of alpha 2(I) procollagen mRNA were visualized after hybridization with 35S-labelled riboprobes. Hybridization signals were associated with alveolar interstitial cells throughout the normal lung, with additional areas of dense hybridization signals observed subpleurally. Three days following administration of bleomycin, there was no apparent change in the pattern of hybridization. By 10 days, foci of intense hybridization signals indicative of gene activation were observed associated with individual cells in the alveolar interstitium. At 21 days, the increase in hybridization signals appeared to be associated with greater numbers of cells rather than highly activated cells. These results demonstrate that procollagen genes are normally expressed in the mouse lung, and that during bleomycin-induced pulmonary fibrosis hybridization signals increase, suggesting that both enhanced gene expression by individual cells and increased numbers of cells expressing the type I procollagen gene are involved in the pathogenetic mechanism.
Platelet-derived growth factor-beta mRNA in human alveolar macrophages in vivo in asthma
Authors: Taylor IK , Sorooshian M , Wangoo A , Haynes AR , Kotecha S , Mitchell DM , Shaw RJ
Published: November 2022

Collagen deposition and myofibroblast proliferation beneath the epithelial basement membrane in patients with asthma is now increasingly recognized, although the molecular pathogenesis remains obscure. We have evaluated messenger ribonucleic acid (mRNA) expression of the profibrotic cytokine, platelet-derived growth factor-beta (PDGF-beta), in alveolar macrophages obtained following fibreoptic bronchoscopy and bronchoalveolar lavage in patients with asthma. Three subject groups were studied: 1) asthmatics using regular inhaled glucocorticoid medication (ASTST, n = 9), 2) asthmatics using intermittent inhaled beta 2-agonist therapy only (ASTBR, n = 10); 3) nonasthmatic control volunteers (n = 10). Alveolar macrophage mRNA was extracted and PDGF-beta mRNA quantified by reverse-transcriptase polymerase chain reaction (PCR) (RT-PCR) and expressed as the ratio to that of a control gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). There were no significant differences in PDGF-beta mRNA expression between the groups, or between all asthmatic (n = 19) and control subjects. Furthermore, there was no correlation between alveolar macrophage PDGF-beta mRNA expression and airway spirometry, or duration of glucocorticoid usage or dose. Thus, in contrast to other fibrotic lung diseases, we found little evidence of enhanced expression of PDGF-beta mRNA in alveolar macrophages in clinically stable bronchial asthma.
Bronchoprotection by salmeterol: cell stabilization or functional antagonism? Comparative effects on histamine- and AMP-induced bronchoconstriction
Authors: Soler M , Joos L , Bolliger CT , Elsasser S , Perruchoud AP
Published: November 2022

Salmeterol provides bronchoprotection against a number of constrictor stimuli for more than 12 h after a single dose. This effect could be due either to functional antagonism at the level of airway smooth muscle or to cell-stabilizing effects of the compound. In this study, we attempted to clarify this mechanism by comparing the effects of salmeterol (50 micrograms), salbutamol (200 micrograms) and placebo on the airway responsiveness to histamine (to assess functional antagonism), and to adenosine 5'-monophosphate (AMP) (to assess additional cell-stabilizing effects), 14 h after drug treatment. Thirteen patients with mild allergic asthma were studied in a double-blind, randomized protocol on 6 days, at least 48 h apart. Forced expiratory volume in one second (FEV1) was measured before and 15 min after inhalation of the study medication. Then, 14 h later (8 a.m. the following morning), a bronchoprovocation test with histamine or AMP was performed. We found that 14 h after inhalation, salmeterol still had a significant effect on FEV1 in comparison to placebo and salbutamol. The provocative dose producing a 20% fall in FEV1 (PD20histamine) was significantly increased after salmeterol, whilst the increase in PD20AMP did not reach significance. The shift in PD20 (in doubling dose steps) induced by salmeterol pretreatment was not different between histamine and AMP. We conclude that the prolonged protective effect of salmeterol occurs via an extended bronchodilating and functional antagonistic action and not via a cell-stabilizing effect.
Nitrazepam in patients with sleep apnoea: a double-blind placebo-controlled study
Authors: Hoijer U , Hedner J , Ejnell H , Grunstein R , Odelberg E , Elam M
Published: November 2022

We wanted to assess whether benzodiazepines worsen sleep apnoea, since their use in such patients has been controversial. Fourteen male patients with mild to moderate obstructive sleep apnoea were investigated in a placebo-controlled, double-blind study evaluating the influence of nitrazepam (NIT) on apnoea frequency and severity. Each patient was given oral nitrazepam 5 or 10 mg, or corresponding placebo, in a randomized order on three separate nights. Wash-out time was one week. A complete sleep study was undertaken at each study night. Eleven patients completed the study. Although there were individuals with marked variability in apnoea index between the three study nights, there was no significant change in apnoea index or minimum arterial oxygen saturation with any of the two nitrazepam dosages studied. Only 3 out of 11 patients had a higher apnoea index after both nitrazepam doses compared to placebo, and in these patients the increase in sleep-disordered breathing was of marginal clinical significance. Nitrazepam caused a modest increase in total sleep time and a decrease in rapid eye movement (REM) sleep. These results demonstrate that nitrazepam does not worsen sleep apnoea in patients with mild to moderate sleep apnoea. The previously reported sleep apnoea promoting effects of benzodiazepines may be restricted to a small subgroup of patients with sleep-disordered breathing.
Hygroscopic condenser humidifiers in chronically tracheostomized patients who breathe spontaneously
Authors: Vitacca M , Clini E , Foglio K , Scalvini S , Marangoni S , Quadri A , Ambrosino N
Published: November 2022

The aim of this study was to test the usefulness of hygroscopic condenser humidifiers on secretion and on inspired gas temperature in tracheostomized patients. Forty spontaneously breathing chronically tracheostomized patients were divided into two groups: Group 1 received a hygroscopic condenser humidifier connected to the tracheostomy, 24 h daily for 10 days; Group 2, without any protection system, was chosen as the control group. The daily number of tracheal suctions, quantity of aspirate and thickness and colouring of secretions was evaluated. At baseline, and at days 5 and 10, patients were submitted to blood gas analysis, respiratory function tests and sputum analysis. The temperature of gases breathed was measured at rest and during a hyperventilation test, with and without the hygroscopic condenser humidifier. Statistically significant differences were found in thickness and colouring of secretions between the two groups during the period of 10 days. Group 2 showed a significantly greater trend in number of bacteria than Group 1. The group with the hygroscopic condenser humidifier showed respiratory function improvement over time for forced expiratory volume in one second (FEV1) and tidal volume (VT), maximal inspiratory pressure (MIP), and maximal voluntary ventilation (MVV) in comparison to the control group, who did not. Significant differences in the temperature between rest and hyperventilation, with and without a hygroscopic condenser humidifier were also found. In conclusion, a hygroscopic condenser humidifier may be useful in chronically tracheostomized patients who breathe spontaneously, improving viscosity and colouring of secretions, preventing further bacterial colonization, heating inspiratory flow, and helping to improve the functional outcome.
Prevalence of asthma and wheeze in Hong Kong schoolchildren: an international comparative study
Authors: Leung R , Bishop J , Robertson CF
Published: November 2022

Comparison of asthma prevalence between populations is difficult because of lack of uniformity of methodology and agreement on the definition. This study aims to determine and compare the prevalence of wheeze and respiratory symptoms in Hong Kong schoolchildren with that in Melbourne children by using identical questionnaires. Schools were randomly selected in different regions of Hong Kong and three age groups (7, 12 and 15 yrs) were chosen for the study. The Chinese version of the questionnaire used in a recent Melbourne survey was distributed to children for completion by their parents. A total of 1,800 questionnaires was issued and 1,689 returned (response rate = 94%). The prevalence of wheeze in the past 12 months was 7 (5.1-8.0), 5 (3.0-6.7) and 4 (1.7-5.6) % for 7, 12 and 15 year olds, respectively. The prevalence of a history of asthma in the respective age groups was 10 (7.1-12.9), 8 (7.5-9.2) and 7 (5.0-9.6) %, respectively. Whilst a history of wheeze ever was more common in boys than in girls and 12 yr olds (14% vs 5%), wheeze in the past 12 months was more common in boys than in girls aged 7 yrs (9 vs 4%). We conclude that the prevalence of wheeze and asthma in school children was low in Hong Kong compared to Melbourne. Environmental differences between the two regions may be important in the pathogenesis.
Protocols for in vivo measurement of the ion transport defects in cystic fibrosis nasal epithelium
Authors: Middleton PG , Geddes DM , Alton EW
Published: November 2022

New treatments for cystic fibrosis (CF), including gene therapy, are currently being assessed. These aim to correct the basic defects of increased sodium absorption and decreased chloride secretion in airway epithelia. Assessment of these bioelectric parameters, particularly in the nasal epithelium, is likely to be used as a measure of treatment efficacy. However, the optimal in vivo protocol to discriminate cystic fibrosis from non-cystic fibrosis subjects is unclear. We have, therefore, compared three protocols for measurement of the cystic fibrosis ion transport defects in vivo in the nasal epithelium. Sodium absorption was measured using both the baseline potential difference and the response to the sodium channel blocker, amiloride. Chloride secretion was assessed in the presence of amiloride, using perfusion with isoprenaline, or terbutaline, or a low chloride solution followed by isoprenaline. Baseline potential difference (PD) and the absolute response to amiloride clearly differentiated the increased sodium absorption in the cystic fibrosis subjects. The responses both to terbutaline (delta PD: non-CF: -0.8 (SEM 0.7) mV; CF: -3.6 (0.5) mV) and isoprenaline (non-CF: 1.5 (0.6) mV; CF: -2.9 (0.6) mV) differentiated the two groups of subjects, but there was considerable overlap of values. Perfusion with a low chloride solution (non-CF: 12.6 (1.2) mV; CF: 0.6 (0.4) mV), as well as subsequent perfusion with isoprenaline (non-CF: 10.0 (1.1) mV; CF: -1.4 (0.4) mV) allowed clear separation of the two groups, with no overlap of values. Some CF subjects showed a transient hyperpolarization to these stimuli, which could clearly be differentiated from the sustained responses seen in non-cystic fibrosis subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of respiratory muscle strength in the intensive care unit
Authors: Moxham J , Goldstone J
Published: November 2022

The measurement of respiratory muscle strength in the intensive care unit (ICU) is potentially useful for the prediction of weaning outcome. An easy and accurate measure would also allow investigation of respiratory muscle weakness in critically ill patients. At present, there is no satisfactory method of strength measurement in the intensive care unit. Vital capacity is a nonspecific, volitional and relatively insensitive measure of strength. True maximum respiratory pressures are difficult to achieve and, in stable patients, results vary greatly both over time and between observers. For these reasons, there are few good data of respiratory muscle strength in the intensive care unit. Of the new techniques being developed, magnetic stimulation of the phrenic nerves, combined with the measurement of transdiaphragmatic, oesophageal, or endotracheal tube pressure, offers the greatest promise.
Evaluation of three different techniques used to measure chest wall movements in children
Authors: Russell RI , Helms PJ
Published: November 2022

Several techniques exist for assessing chest wall movements in children, that incorporate different measurement principles. Although the output from such devices appears very similar, the comparability of data from different devices needs to be evaluated. We have investigated the simultaneous measurement of chest wall movement using three different devices in 12 children recovering from intensive care. The devices used were inductance plethysmography (assessing thoracic cross-sectional area), magnetometers (assessing thoracic diameter), and a Hall device strain guage (assessing thoracic circumference). Measurements of respiratory timing and of phase angle between rib cage and abdomen in these patients showed a close agreement between devices in ventilated patients. However, occasional inconsistencies occurred in patients who were breathing spontaneously. We suggest that it may not always be appropriate to directly compare data on chest wall movements in children recorded using different measurement techniques. The best method of measurement varies with the clinical picture.
Platypnoea syndrome caused by atrial septal aneurysm
Authors: Frans E , Timmermans C , Herregods MC , De Geest H , Daenen W , Delanote M , Decramer M
Published: November 2022

A patient with platypnoea after right pneumonectomy and radiotherapy is described. On transoesophageal contrast echocardiography and cardiac catheterization, an atrial septal aneurysm with interatrial right-to-left shunting was detected. Symptoms disappeared after surgical correction. To the best of our knowledge, this is the first report of a patient with a septal aneurysm and severe platypnoea.
Attenuation of hypoxic ventilatory response after recovery from chronic hypoxaemia in a case of pulmonary A-V fistula
Authors: Kobayashi S , Nishimura M , Miyamoto K , Kawakami Y
Published: November 2022

We studied respiratory chemosensitivity in a patient with pulmonary arterio-venous (AV) fistulae before and after surgical removal of the lesions. The patient had had moderate hypoxaemia with hyperventilation before the operation. When first studied, 21 days following surgery, both hypoxic and hypercapnic ventilatory responses were found to be lower than they were preoperatively. During the next 1-2 months, hypoxic ventilatory response continued to fall significantly to a steady value, whereas hypercapnic response showed no further fall. There has been no previous report of such a phenomenon in humans after recovery from chronic hypoxaemia.
Two-year effectiveness of erenumab in resistant chronic migraine: a prospective real-world analysis
Authors: Andreou Anna P. , Fuccaro Matteo , Hill Bethany , Murphy Madeleine , Caponnetto Valeria , Kilner Rachael , Lambru Giorgio
Published: November 2022

Background

Controlled and real-world evidence have demonstrated the efficacy of calcitonin gene related peptide (CGRP) monoclonal antibodies (MABs) in migraine. However, data on the over-one-year sustained effectiveness of CGRP MABs in resistant chronic migraine (CM) is sparse. 

Methods

This is a two-year real-world prospective analysis of an ongoing single centre audit conducted in patients with resistant CM. Patients received monthly erenumab for six months before assessing its effectiveness. Responders were considered those who achieved at least 30% reduction in monthly migraine days (MMD) by month 6, compared to baseline. Secondary outcomes were also analysed, including changes of the Headache Impact Test version 6 (HIT-6).

Results

One hundred sixty-four patients [135 (82.3%) females; mean age 46 SD 14) years] were included in the audit and 160 patients analysed. Patients had failed a mean of 8.4 preventive treatments at baseline. At month 6, 76 patients (48%) were 30% responders to erenumab, 50 patients (31%) were 50% responders and 25 (15%) were 75% responders. The mean reduction in MMD at month 6 was 7.5 days compared to baseline (P < 0.001). At month 12 and month 18, 61 patients (38%) and 52 patients (33%) remained 30% responders respectively. At month 24, 36 patients (23%) remained 30% responders, 25 patients (16%) and 13 patients (8%) were respectively 50% and 75% responders. Compared to 95% of patients at baseline, at months 6, 12 and 24, 46%, 29% and 16% of responders respectively had severe disability. At least one adverse event at month 6, 12, 18 and 24 was reported by 49%, 19%, 11% and 3% of patients. By month 6, 13% of patients discontinued the treatment because of side effects, often constipation.

Conclusions

Long-term sustained effectiveness of erenumab was reported only by a minority of resistant CM patients. Although more research in resistant migraine is needed, Erenumab can provide long-term meaningful reduction in migraine load and migraine-related disability in some patients.
Morphospecies and molecular diversity of ‘lace corals’: the genus Reteporella (Bryozoa: Cheilostomatida) in the central North Atlantic Azores Archipelago
Authors: Baptista Lara , Berning Björn , Curto Manuel , Waeschenbach Andrea , Meimberg Harald , Santos António M. , Ávila Sérgio P.
Published: November 2022

Background

As in most bryozoans, taxonomy and systematics of species in the genus Reteporella Busk, 1884 (family Phidoloporidae) has hitherto almost exclusively been based on morphological characters. From the central North Atlantic Azores Archipelago, nine Reteporella species have historically been reported, none of which have as yet been revised. Aiming to characterise the diversity and biogeographic distribution of Azorean Reteporella species, phylogenetic reconstructions were conducted on a dataset of 103 Azorean Reteporella specimens, based on the markers cytochrome C oxidase subunit 1, small and large ribosomal RNA subunits. Morphological identification was based on scanning electron microscopy and complemented the molecular inferences.

Results

Our results reveal two genetically distinct Azorean Reteporella clades, paraphyletic to eastern Atlantic and Mediterranean taxa. Moreover, an overall concordance between morphological and molecular species can be shown, and the actual bryozoan diversity in the Azores is greater than previously acknowledged as the dataset comprises three historically reported species and four putative new taxa, all of which are likely to be endemic. The inclusion of Mediterranean Reteporella specimens also revealed new species in the Adriatic and Ligurian Sea, whilst the inclusion of additional phidoloporid taxa hints at the non-monophyly of the genus Reteporella.

Conclusion

Being the first detailed genetic study on the genus Reteporella, the high divergence levels inferred within the genus Reteporella and family Phidoloporidae calls for the need of further revision. Nevertheless, the overall concordance between morphospecies and COI data suggest the potential adequacy of a 3% cut-off to distinguish Reteporella species. The discovery of new species in the remote Azores Archipelago as well as in the well-studied Mediterranean Sea indicates a general underestimation of bryozoan diversity. This study constitutes yet another example of the importance of integrative taxonomical approaches on understudied taxa, contributing to cataloguing genetic and morphological diversity.
iTRAQ-based proteomic analysis of Deinococcus radiodurans in response to 12C6+ heavy ion irradiation
Authors: Gao Yuan , Li Naikang , Zhou Yanxia , Zhang Zhenpeng , Zhang Yao , Fan Pengcheng , Zhou Hangfan , Zhang Tao , Chang Lei , Gao Huiying , Li Yanchang , Kang Xianjiang , Xie Qiong , Lyu Zhitang , Xu Ping
Published: November 2022

Background

Deinococcus radiodurans (D. radiodurans) is best known for its extreme resistance to diverse environmental stress factors, including ionizing radiation (IR), ultraviolet (UV) irradiation, oxidative stress, and high temperatures. Robust DNA repair system and antioxidant system have been demonstrated to contribute to extreme resistance in D. radiodurans. However, practically all studies on the mechanism underlying D. radiodurans’s extraordinary resistance relied on the treated strain during the post-treatment recovery lag phase to identify the key elements involved. The direct gene or protein changes of D. radiodurans after stress have not yet been characterized.

Results

In this study, we performed a proteomics profiling on D. radiodurans right after the heavy ion irradiation treatment, to discover the altered proteins that were quickly responsive to IR in D. radiodurans. Our study found that D. radiodurans shown exceptional resistance to 12C6+ heavy ion irradiation, in contrast to Escherichia coli (E.coli) strains. By using iTRAQ (Isobaric Tags for Relative and Absolute Quantitation)-based quantitative mass spectrometry analysis, the kinetics of proteome changes induced by various dosages of 12C6+ heavy ion irradiation were mapped. The results revealed that 452 proteins were differentially expressed under heavy ion irradiation, with the majority of proteins being upregulated, indicating the upregulation of functional categories of translation, TCA cycle (Tricarboxylic Acid cycle), and antioxidation regulation under heavy ion irradiation.

Conclusions

This study shows how D. radiodurans reacts to exposure to 12C6+ heavy ion irradiation in terms of its overall protein expression profile. Most importantly, comparing the proteome profiling of D. radiodurans directly after heavy ion irradiation with research on the post-irradiation recovery phase would potentially provide a better understanding of mechanisms underlying the extreme radioresistance in D. radiodurans.
Rescaling pain intensity measures for meta-analyses of analgesic medicines for low back pain appears justified: an empirical examination from randomised trials
Authors: Wewege Michael A. , Jones Matthew D. , Williams Sam A. , Kamper Steven J. , McAuley James H.
Published: November 2022

Objective

Meta-analyses of analgesic medicines for low back pain often rescale measures of pain intensity to use mean difference (MD) instead of standardised mean difference for pooled estimates. Although this improves clinical interpretability, it is not clear whether this method is justified. Our study evaluated the justification for this method.

Methods

We identified randomised clinical trials of analgesic medicines for adults with low back pain that used two scales with different ranges to measure the same construct of pain intensity. We transformed all data to a 0–100 scale, then compared between-group estimates across pairs of scales with different ranges.

Results

Twelve trials were included. Overall, differences in means between pain intensity measures that were rescaled to a common 0–100 scale appeared to be small and randomly distributed. For one study that measured pain intensity on a 0–100 scale and a 0–10 scale; when rescaled to 0–100, the difference in MD between the scales was 0.8 points out of 100. For three studies that measured pain intensity on a 0–10 scale and 0–3 scale; when rescaled to 0–100, the average difference in MD between the scales was 0.2 points out of 100 (range 5.5 points lower to 2.7 points higher). For two studies that measured pain intensity on a 0–100 scale and a 0–3 scale; when rescaled to 0–100, the average difference in MD between the scales was 0.7 points out of 100 (range 6.2 points lower to 12.1 points higher). Finally, for six studies that measured pain intensity on a 0–100 scale and a 0–4 scale; when rescaled to 0–100, the average difference in MD between the scales was 0.7 points (range 5.4 points lower to 8.3 points higher).

Conclusion

Rescaling pain intensity measures may be justified in meta-analyses of analgesic medicines for low back pain. Systematic reviewers may consider this method to improve clinical interpretability and enable more data to be included.

Study registration/data availability

Open Science Framework (osf.io/8rq7f).
AutoScore-Ordinal: an interpretable machine learning framework for generating scoring models for ordinal outcomes
Authors: Saffari Seyed Ehsan , Ning Yilin , Xie Feng , Chakraborty Bibhas , Volovici Victor , Vaughan Roger , Ong Marcus Eng Hock , Liu Nan
Published: November 2022

Background

Risk prediction models are useful tools in clinical decision-making which help with risk stratification and resource allocations and may lead to a better health care for patients. AutoScore is a machine learning–based automatic clinical score generator for binary outcomes. This study aims to expand the AutoScore framework to provide a tool for interpretable risk prediction for ordinal outcomes.

Methods

The AutoScore-Ordinal framework is generated using the same 6 modules of the original AutoScore algorithm including variable ranking, variable transformation, score derivation (from proportional odds models), model selection, score fine-tuning, and model evaluation. To illustrate the AutoScore-Ordinal performance, the method was conducted on electronic health records data from the emergency department at Singapore General Hospital over 2008 to 2017. The model was trained on 70% of the data, validated on 10% and tested on the remaining 20%.

Results

This study included 445,989 inpatient cases, where the distribution of the ordinal outcome was 80.7% alive without 30-day readmission, 12.5% alive with 30-day readmission, and 6.8% died inpatient or by day 30 post discharge. Two point-based risk prediction models were developed using two sets of 8 predictor variables identified by the flexible variable selection procedure. The two models indicated reasonably good performance measured by mean area under the receiver operating characteristic curve (0.758 and 0.793) and generalized c-index (0.737 and 0.760), which were comparable to alternative models.

Conclusion

AutoScore-Ordinal provides an automated and easy-to-use framework for development and validation of risk prediction models for ordinal outcomes, which can systematically identify potential predictors from high-dimensional data.
Identifying complex patients in family medicine for potential benefit from a case manager: a short questionnaire derived from the INTERMED Self-Assessment (IMSA) questionnaire
Authors: Cohidon Christine , Gallay Emilie , Wild Pascal , Stiefel Friedrich , Bourquin Céline , Senn Nicolas
Published: November 2022

Purpose

To investigate how useful the Intermed-Self Assessment (IMSA) questionnaire and its components were for identifying which patient candidates would benefit most from case management (CM) in general practice.

Methods

The study was carried out in a group family medicine practice in Lausanne comprising seven GPs and four medical assistants, from February to April 2019. All the patients attending the practice between February and April 2019 were invited to complete the IMSA questionnaire. Additionally, their GPs were asked for their opinions on the potential benefits of each patient being assigned a case manager. Each IMSA item’s value has been assessed as a predictor of GPs’ opinions by using multivariate logistic models. A score including items retained as predictor was built.

Results

Three hundred and thirty one patients participated in the study (participation rate: 62%). Three items from the 20 item IMSA were sufficient to predict GPs’ opinions about whether their patients could be expected to benefit if assigned a case manager. Those items addressed the patient’s existing chronic diseases (item1), quality of life in relation to existing diseases (item 3), and their social situation (item 9). Using these three items as a score, a cut-off at 4 gave a sensitivity of 70% (ability to correctly identify patients who could benefit from a CM) and specificity of 73% (ability to correctly identify patients who should not benefit from a CM) and concerned about one patient in two.

Conclusion

Identifying complex patients suitable for case management remains a challenge for primary care professionals. This paper describes a novel approach using a structured process of combining the results of standardized tools such as the one defined in this study, and the experience of the primary care team.
Serum zinc values, ankle brachial index and mortality in hemodialysis patients
Authors: Knehtl Maša , Piko Nejc , Ekart Robert , Hojs Radovan , Bevc Sebastjan
Published: November 2022

Introduction

The atherosclerotic state of haemodialysis (HD) patients may be influenced by heavy metals. The purpose of our study was to assess the relationship between serum zinc (Zn) ankle brachial index (ABI) as a non-invasive diagnostic tool for atherosclerosis, and mortality in chronic haemodialysis (HD) patients.

Methods

Sixty one HD patients were included (mean age 61.2 ± 13.8 years). The ABI was measured with an automated measuring device (ABPI MD, MESI®, Slovenia). Two groups of patients were formed based on the median value of Zn (14.1 mcmol/l). The average observation time was 2.8 years. Comorbidities (arterial hypertension (AH), diabetes mellitus (DM), dyslipidaemia), smoking and oral nutritional supplements (ONS) consumption were noted. Survival rates were analysed by Kaplan–Meier and Cox regression was used to determine the influence of Zn, ABI, AH, DM, dyslipidaemia, smoking and ONS.

Results

Zn values were between 9.2 and 23.5 mcmol/l (14.4 ± 2.34), ABI values ranged from 0.8 to 1.4 (1.14 ± 0.12). Patients with lower Zn values had lower ABI (p = 0.036). Mean survival time of patients with higher Zn values was 985 days ± 277 days and with lower Zn values 1055 ± 143 days. Six (19.4%) patients with lower Zn and five (16.7%) patients with higher Zn died. We found statistically insignificant lower survival in patients with higher Zn. We failed to find any predictor of all-cause mortality, except for ONS consumption (95% CI 1.6–33.3; p = 0.012).

Conclusions

Lower Zn is associated with lower ABI in HD patients, but we found no impact of Zn on patient survival.
Prediction model of gonadotropin starting dose and its clinical application in controlled ovarian stimulation
Authors: Hua Liang , Zhe Yang , Jing Yang , Fujin Shen , Jiao Chen , Liu Liu
Published: November 2022

Background

Selecting an appropriate and personalized Gn starting dose (GSD) is an essential procedure for determining the quality and quantity of oocytes in the controlled ovarian stimulation (COS) process of the in-vitro fertilization (IVF) treatment cycle. The current approach for determining the GSD is mainly based on the experience of a clinician, lacking unified and scientific standards. This study aims to establish a prediction model of GSD, based on which good COS outcomes can be achieved with the influencing factors comprehensively evaluated quantitatively.

Material and methods

We collected a total of 1555 patients undergoing the first oocytes retrieving cycle and conducted correlation analysis to find the significant factors related to the GSD. Two GSD models are built based on two popular machine learning approaches, and the one with better model performance is selected as the final model. Finally, clinical application and validation were conducted to verify the effectiveness of the proposed model.

Results

(1) Age, duration of infertility, type of infertility, body mass index (BMI), antral follicle count (AFC), basal follicle stimulating hormone (bFSH), estradiol (E2), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and COS treatment regimen were closely related to the GSD (P < 0.05). (2) The selected model has good modeling performance in terms of both root mean square error (RMSE) (29.87 ~ 34.21) and regression coefficient R (0.947 ~ 0.953). (3) A comprehensive evaluation of influencing factors for GSD is conducted and shows that the top four most significant factors are age, AMH, AFC, and BMI. (4) The proposed GSD can approximate the actual value well in the clinical application, with the mean absolute error of only 11.26 units, and the recommended results can prompt the number of oocytes retrieved (NOR) close to the optimal number.

Conclusion

Modeling the GSD value with machine learning approaches is feasible and effective, and the proposed model has good clinical application for determining the GSD in the IVF treatment cycle.
Weight gain trajectories patterns from pregnancy to early postpartum: identifying women at risk and timing to prevent weight regain
Authors: Muñoz-Manrique Cinthya , Trejo-Valdivia Belem , Hernández-Cordero Sonia , Cantoral Alejandra , Deierlein Andrea L. , Colicino Elena , Niedzwiecki Megan M. , Wright Robert O. , Baccarelli Andrea A. , Téllez-Rojo Martha María
Published: November 2022

Background

Woman's weight changes during pregnancy and postpartum contribute to obesity and health outcomes later in life. This study aimed to identify and characterize weight change trajectories from pregnancy to one year postpartum among adult women.

Methods

We used data from an ongoing cohort of healthy adult women (n = 819) with singleton pregnancies from 2007 – 2011. Sociodemographic data, pre-pregnancy body weight, and sedentary and breastfeeding practices were collected using questionaries applied by trained professionals. We applied a group-based trajectory modeling to distinguish weight change measured in the second and third trimesters of pregnancy and at one month, six, and 12 months postpartum. Multinomial regression models were run to characterize each trajectory.

Results

We identified six weight change trajectories with the main difference in the patterns followed after one month of delivery. One in three women (36.7%) was classified in some of the three postpartum weight gain trajectories and regained weight from the second trimester of the first year postpartum. Women who followed some of these trajectories were more likely to have higher age, obesity before pregnancy, < 10 years of schooling, and partner, compared with women (10.7%,n = 87) in a postpartum sustained-fast-lost-weight trajectory (p < 0.05).

Conclusions

Women with obesity before pregnancy have higher odds of regaining gestational weight after delivery without reaching their pre-pregnancy weight. The first six months postpartum are crucial to establishing obesity prevention strategies. Further research is needed to evaluate the effect of the interventions that prevent substantial weight gain through reproductive years in high-risk women.
Community social capital and the health-related quality of life among empty-nest elderly in western China: moderating effect of living arrangements
Authors: Zhu Huan , He Lei , Peng Jiayi , LI Xingyue , Gao Bo , Zhou Huan , Wan Yang
Published: November 2022

Background:

At present, the empty nest phenomenon is becoming more and more serious in the world, especially in China, and its health problems deserve attention. Therefore, the purpose of this study is to explore the impact of community social capital on the health-related quality of life of empty-nest elderly.

Methods:

The study used data collected from a survey study conducted between 2018 and 2019 in Sichuan province, China, with 638 empty-nest elderly meeting our criteria. SF-12 scale and self-made social capital scale were used to evaluate the health-related quality of life and community social capital of empty-nest elderly. Through descriptive statistical analysis, bivariate analysis and hierarchical multiple regression model, this study analyzes the relationship between community social capital and health-related quality of life of empty-nest elderly. Considering the role of living arrangements, this study further uses the simple effect analysis method to explore the moderating role of living arrangements.

Results:

After controlling the relevant variables, the cognitive social capital (CSC) of empty-nest elderly had a positive relationship with the physical health summary (PCS) (β = 0.188, p＜0.001) and mental health summary (MCS) (β = 0.205, p＜0.001). No effect of structural social capital on quality of life was found as a result. Living arrangements played a moderation effect on the relationship between CSC and MCS (β=-2.018, p＜0.05). The MCS score of high CSC group (55.516 ± 0.757) was significantly higher than that of low CSC group (49.383 ± 0.722).

Conclusion:

The results suggest empty-nest elderly has poorer physical health and weaker structural social capital, while the cognitive social capital has a greater positive impact on their quality of life. Targeted interventions to enhance community social capital may be beneficial to improve health status of this vulnerable population.
Childhood maltreatment and suicidal ideation in Chinese children and adolescents: the mediating role of mindfulness
Authors: Liang Xuemeng , Chang Wei , Ran Hailiang , Fang Die , Che Yusan , Wang Sifan , Chen Lin , Sun Hao , Lu Jin , Xiao Yuanyuan
Published: November 2022

Background

Childhood maltreatment (CM) has been associated with suicidal ideation (SI) in children and adolescents, yet the mediating role of mindfulness in this association remains unclear. This study aims to test the mediation of mindfulness in CM-SI association among a large sample of Chinese children and adolescents.

Methods

A population-based cross-sectional study of 3455 children and adolescents aged 10–17 years from southwest China Yunnan province was conducted. Information from the participants was collected by using a comprehensive self-administered questionnaire. The Chinese version of the Childhood Trauma Questionnaire (CTQ), Five Facet Mindfulness Questionnaire (FFMQ), and the Beck Scale for Suicidal Ideation (BSSI) were used to measure CM, mindfulness and SI. Univariate and multivariate binary logistic regression models were used to estimate the crude and adjusted associations between CM, mindfulness and SI (one-week, one-year, lifetime). Pathway analysis was subsequently performed to test the mediation of mindfulness in CM-SI association.

Results

The findings showed that mindfulness, CM and SI were significantly correlated with each other (p < 0.05). Mindfulness is a significant mediator in CM-SI association, accounted for 7.5, 11.4, and 17.6% of the total associations for one-week SI, one-year SI, and lifetime SI, respectively. For the five types of CM, the highest level of mediation via mindfulness had been found for physical neglect (PN) and one-year SI (34.3%), followed by emotional neglect (EN) and one-year SI (30.2%), sexual abuse (SA) and one-year SI (25.4%).

Conclusions

Our study findings highlight the intervention potential of mindfulness in preventing CM associated suicidal risk. Future longitudinal studies are warranted to corroborate the effectiveness of mindfulness-based intervention for Chinese children and adolescents.
Application of logistic differential equation models for early warning of infectious diseases in Jilin Province
Authors: Yang Tianlong , Wang Yao , Yao Laishun , Guo Xiaohao , Hannah Mikah Ngwanguong , Liu Chan , Rui Jia , Zhao Zeyu , Huang Jiefeng , Liu Weikang , Deng Bin , Luo Li , Li Zhuoyang , Li Peihua , Zhu Yuanzhao , Liu Xingchun , Xu Jingwen , Yang Meng , Zhao Qinglong , Su Yanhua , Chen Tianmu
Published: November 2022

Background

There is still a relatively serious disease burden of infectious diseases and the warning time for different infectious diseases before implementation of interventions is important. The logistic differential equation models can be used for predicting early warning of infectious diseases. The aim of this study is to compare the disease fitting effects of the logistic differential equation (LDE) model and the generalized logistic differential equation (GLDE) model for the first time using data on multiple infectious diseases in Jilin Province and to calculate the early warning signals for different types of infectious diseases using these two models in Jilin Province to solve the disease early warning schedule for Jilin Province throughout the year.

Methods

Collecting the incidence of 22 infectious diseases in Jilin Province, China. The LDE and GLDE models were used to calculate the recommended warning week (RWW), the epidemic acceleration week (EAW) and warning removed week (WRW) for acute infectious diseases with seasonality, respectively.

Results

Five diseases were selected for analysis based on screening principles: hemorrhagic fever with renal syndrome (HFRS), shigellosis, mumps, Hand, foot and mouth disease (HFMD), and scarlet fever. The GLDE model fitted the above diseases better (0.80 ≤ R2 ≤ 0.94, P <  0. 005) than the LDE model. The estimated warning durations (per year) of the LDE model for the above diseases were: weeks 12–23 and 40–50; weeks 20–36; weeks 15–24 and 43–52; weeks 26–34; and weeks 16–25 and 41–50. While the durations of early warning (per year) estimated by the GLDE model were: weeks 7–24 and 36–51; weeks 13–37; weeks 11–26 and 39–54; weeks 23–35; and weeks 12–26 and 40–50.

Conclusions

Compared to the LDE model, the GLDE model provides a better fit to the actual disease incidence data. The RWW appeared to be earlier when estimated with the GLDE model than the LDE model. In addition, the WRW estimated with the GLDE model were more lagged and had a longer warning time.