bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid implementation of triaging system for assessment of breast referrals from primary care centres during the COVID-19 pandemic
Authors: Shetty G , Datta U , Rea I , Rai S , Hwang M-J , Hoar F , Sintler M , Mirza M , Husain A , Tan M 
Published: May 2023

Objective The aim of this study was to establish a triaging system for assessment of breast referrals from primary care to ensure safe and effective breast services without compromising breast cancer management. Background COVID-19 was officially declared a global pandemic on 11 March 2020, and with no effective treatment available, preventing spread has been paramount. Previously, all referrals from primary care were seen in the rapid-access breast clinic (RABC). Clinic appointments exposed patients and healthcare professionals to risk. Method Initial triage during the lockdown was in line with national governing body guidance, rejected low risk referrals and streamed remaining patients through a telephone consultation to RABC or discharge. A modified triage pathway streamed all patients through virtual triage to RABC, telephone clinic or discharge with advice and guidance categories. Demographics, reasons for referral and outcomes data were collected and presented as median with range and frequency with percentages. Results Initial triage (23 March–23 April 2020) found fewer referrals with a higher percentage of breast cancer diagnoses. Modified triage (22 June–17 July 2020) resulted in a 35.1% (99/282) reduction in RABC attendance. Overall cancer detection rate remained similar at 4.2% of all referrals pre-COVID (18/429) and 4.3% (12/282) during modified triage. After six months follow-up of patients not seen in RABC during the modified triage pathway, 18 patients were re-referred to RABC and none were diagnosed with cancer. Conclusion A modified triage pathway has the potential to improve triage efficiency and prevent unnecessary visits during the COVID-19 pandemic. Further refinement of pathway is feasible in collaboration with primary care.
Laparoscopy uptake for paediatric appendicectomy: a comparison of general surgeons versus specialist paediatric surgeons in England from 1997 to 2015
Authors: Bethell GS , Adams S , Johnson T , Hall NJ , Stanton MP 
Published: May 2023

Introduction Laparoscopy is used in as many as 95% of adult appendicectomies. There is level I evidence showing that it reduces wound infection, postoperative ileus and length of inpatient stay in children compared with the open approach. The aim of this study was to report the uptake of laparoscopy for paediatric appendicectomy in England and to determine whether this was similar for general surgeons (GS) and specialist paediatric surgeons (SPS). Methods Hospital Episode Statistics data were obtained for all children aged <16 years who had an OPCS 4.6 code for emergency appendicectomy from 1997 to 2015 (18 years). Data are analysed to compare rate of laparoscopic vs open procedures for GS and SPS over time and to investigate factors associated with the use of laparoscopy. Results There were 196,987 appendicectomies and where specialty was available, 133,709 (79%) cases were undertaken by GS and 35,141 (21%) by SPS. The rate of cases undertaken with laparoscopy for both specialties combined increased from 0.8% in 1998 to 50% in 2014 (p<0.0001). In 2014, this rate was 41% for GS compared with 71% for SPS (p<0.0001). Female gender (odds ratio (OR)=1.84, 95% confidence interval (CI) 1.80–1.90), increasing age (OR=1.18, 95% CI 1.18–1.19 per year) and treatment by SPS (OR=3.71, 95% CI 3.60–3.82) were all factors positively associated with use of laparoscopy in multivariate analysis. Conclusions There has been a vast increase in the proportion of appendicectomies undertaken laparoscopically in children. Despite adjusting for patient factors, laparoscopy was used significantly less by GS when compared with SPS. This difference is most apparent in younger children.
High incidence of dyspnoea and pulmonary aspiration in giant hiatus hernia: a previously unrecognised cause of dyspnoea
Authors: Mugino M , Little SC , Van der Wall H , Falk GL 
Published: May 2023

Introduction Dyspnoea is common in patients with giant paraoesophageal hernia (PEH). Pulmonary aspiration has not previously been recognised as a significant contributory factor. Aspiration pneumonia in association with both gastro-oesophageal reflux disease (GORD) and PEH has a high mortality rate. There is debate about routine anti-reflux measures with surgical repair. Reflux aspiration has been examined in a consecutive cohort using scintigraphic scanning and symptoms. Methods Reflux aspiration scintigraphy (RASP) results and symptoms were evaluated in consecutive patients with PEH managed in our service between January 2012 and March 2017. Results PEH was diagnosed in 96 patients. Preoperative reflux pulmonary scanning was performed in 70 patients: 54 were female (77.1%) and the mean age was 68 years (range 49–85). Dyspnoea was the most common symptom (77.1%), and a symptomatic history of aspiration was seen in 18 patients (25.7%). Clinical aspiration was confirmed by RASP in 13 of these cases. Silent RASP aspiration occurred in a further 27 patients without clinical symptoms. RASP was negative in five patients with clinical symptoms of aspiration. No aspiration by either criterion was present in 27 patients. Dysphagia was negatively related to aspiration on RASP (p<0.01), whereas dyspnoea was not (p=0.857). Conclusion GORD, dyspnoea and silent pulmonary aspiration are frequent occurrences in the presence of giant PEH. Subjective aspiration was the most specific and positive predictor of pulmonary aspiration. Dyspnoea in PEH patients may be caused by pulmonary aspiration, cardiac compression and gas trapping. The high rate of pulmonary aspiration in PEH patients may support anti-reflux repair.
Perioperative administration of tranexamic acid in hip fracture surgery (The PATHS study): national audit of current practice
Authors: Berg AJ , Naylor T , Johnson DS ,   The PATHS Study Collaborators
Published: May 2023

Introduction Neck of femur fractures (NOFF) are associated with significant morbidity and mortality, exacerbated by anaemia. Evidence indicates tranexamic acid (TXA) administration in NOFF surgery reduces blood loss and transfusion requirements, without increasing complications. The aim of this study was to establish current TXA administration practice in patients undergoing surgery for NOFF in the UK. Methods We conducted a multicentre prospective study within the UK over a two-week period in March 2019. Pre-, intra- and postoperative data were collected locally and analysed centrally. Results Data for 917 patients were submitted from 66 institutions. Of those eligible, 48.0% received TXA perioperatively. Administration rates varied from 0 to 100%. Significantly greater numbers undergoing arthroplasty received TXA (57.6%) compared with internal fixation (38.4%, p<0.01). Some 15.2% of institutions had a protocol for TXA use in NOFF. Patients treated in these units were significantly more likely to receive TXA (86.7%) than those who were not (41.2% p<0.01). Of those receiving TXA, 92.3% were given 1g intravenously (IV) at anaesthetic administration. Conclusions Despite supportive evidence for its use, a wide variation in the administration of TXA between hospitals and procedures has been demonstrated. Administration rates were higher for arthroplasty than for fixation procedures. Most centres do not have a protocol guiding TXA administration. We recommend administration of 1g IV TXA perioperatively for patients undergoing NOFF surgery, where not contraindicated, unless future randomised controlled trials support an alternative regimen. We recommend units include their own locally agreed TXA policy within a written protocol for the care of NOFF patients.
Infant mortality and growth failure after oral azithromycin among low birthweight and underweight neonates: A subgroup analysis of a randomized controlled trial
Authors: Bountogo Mamadou , Sié Ali , Zakane Alphonse , Compaoré Guillaume , Ouédraogo Thierry , Brogdon Jessica , Lebas Elodie , Nyatigo Fanice , Medvedev Melissa M. , Arnold Benjamin F. , Lietman Thomas M. , Oldenburg Catherine E. ,   for the NAITRE Study Team
Published: May 2023

Background
Low birthweight (birthweight <2500 grams, g) and underweight (weight-for-age Z-score, WAZ, < -2) infants have higher risk of poor outcomes compared to their well-nourished peers. We evaluated the role of azithromycin for reducing mortality and improving growth outcomes in low birthweight and/or underweight infants.

Methods
Infants aged 8–27 days of age weighing ≥2500 g at enrollment in Burkina Faso were randomized 1:1 to a single, oral dose of azithromycin (20 mg/kg) or matching placebo. We evaluated mortality and anthropometric outcomes in four subgroups: 1) both low birthweight and underweight at enrollment; 2) low birthweight-only; 3) underweight-only; 4) neither low birthweight nor underweight.

Findings
Of 21,832 enrolled infants, 21,320 (98%) had birthweight measurements and included in this analysis. Of these, 747 (3%) were both low birthweight and underweight, 972 (5%) were low birthweight-only, 825 (4%) were underweight-only, and 18,776 (88%) were neither low birthweight nor underweight. Infants who were both low birthweight and underweight receiving azithromycin had lower odds of underweight at 6 months compared to placebo (OR 0.65, 95% CI 0.44 to 0.95), but the treatment group by subgroup interaction was not statistically significant (P = 0.06). We did not find evidence of a difference between groups for other outcomes in any subgroup.

Interpretation
Azithromycin may have some growth-promoting benefits for the highest risk infants, but we were unable to demonstrate a difference in most outcomes in low birthweight and underweight infants. As a secondary analysis of a trial, this study was underpowered for rare outcomes such as mortality.

Trial registration
ClinicalTrials.gov NCT03682653.
Multi-omic modeling of antidepressant response implicates dynamic immune and inflammatory changes in individuals who respond to treatment
Authors: Fuh Shih-Chieh , Fiori Laura M. , Turecki Gustavo , Nagy Corina , Li Yue 
Published: May 2023

Background
Major depressive disorder (MDD) is a leading cause of disability worldwide, and is commonly treated with antidepressant drugs (AD). Although effective, many patients fail to respond to AD treatment, and accordingly identifying factors that can predict AD response would greatly improve treatment outcomes. In this study, we developed a machine learning tool to integrate multi-omic datasets (gene expression, DNA methylation, and genotyping) to identify biomarker profiles associated with AD response in a cohort of individuals with MDD.

Materials and methods
Individuals with MDD (N = 111) were treated for 8 weeks with antidepressants and were separated into responders and non-responders based on the Montgomery–Åsberg Depression Rating Scale (MADRS). Using peripheral blood samples, we performed RNA-sequencing, assessed DNA methylation using the Illumina EPIC array, and performed genotyping using the Illumina PsychArray. To address this rich multi-omic dataset with high dimensional features, we developed integrative Geneset-Embedded non-negative Matrix factorization (iGEM), a non-negative matrix factorization (NMF) based model, supplemented with auxiliary information regarding gene sets and gene-methylation relationships. In particular, we factorize the subjects by features (i.e., gene expression or DNA methylation) into subjects-by-factors and factors-by-features. We define the factors as the meta-phenotypes as they represent integrated composite scores of the molecular measurements for each subject.

Results
Using our model, we identified a number of meta-phenotypes which were related to AD response. By integrating geneset information into the model, we were able to relate these meta-phenotypes to biological processes, including a meta-phenotype related to immune and inflammatory functions as well as other genes related to depression or AD response. The meta-phenotype identified several genes including immune interleukin 1 receptor like 1 (IL1RL1) and interleukin 5 receptor (IL5) subunit alpha (IL5RA), AKT/PIK3 pathway related phosphoinositide-3-kinase regulatory subunit 6 (PIK3R6), and sphingomyelin phosphodiesterase 3 (SMPD3), which has been identified as a target of AD treatment.

Conclusions
The derived meta-phenotypes and associated biological functions represent both biomarkers to predict response, as well as potential new treatment targets. Our method is applicable to other diseases with multi-omic data, and the software is open source and available on Github (https://github.com/li-lab-mcgill/iGEM).
Validation and the associated factors of the Malay version of systemic lupus erythematosus-specific health-related quality of life questionnaires (SLEQoL and LupusQoL)
Authors: Ahmad Pouzi Nur Aqeelah , Shaharir Syahrul Sazliyana , Mohd Tamil Azmi , Mustafar Ruslinda , Ahmad Maulana Suhaida , Mageswaren Eashwary , Wan Ghazali Wan Syamimee 
Published: May 2023

ObjectivesTo assess the reliability and validity of two disease-specific questionnaires that assess the quality of life (QoL) among patients with Systemic Lupus Erythematosus (SLE); SLEQoL and LupusQoL in Malay language. This study also identified the factors affecting each domain of the questionnaires.MethodsThis cross-sectional study was conducted from June 2021 until April 2022, and SLE patients were recruited to complete the SLEQoL, LupusQoL and Short Form Health Survey (SF-36) in Malay language. Disease activity were recorded using the modified SLE Disease Activity Index (M- SLEDAI) and British Isles Lupus Assessment Group 2004 (BILAG-2004) index. Presence of organ damage was determined using the SLICC Damage index. Cronbach’s alpha was calculated to determine internal consistency while exploratory factor analysis was done to determine the construct validity. Concurrent validity was evaluated using correlation with SF-36. Multiple linear regression analysis was deployed to determine the factors affecting each domain of SLEQoL and LupusQoL.ResultsA total of 125 subjects were recruited. The Cronbach’s α value for the Malay-SLEQoL (M-SLEQoL) and Malay-LupusQOL (M-LupusQoL) was 0.890 and 0.944 respectively. Exploratory factor analysis found formation of similar number of components with the original version of questionnaires and all items have good factor loading of >0.4. Both instruments also had good concurrent validity with SF-36. M-SLEQoL had good correlations with BILAG-2004 and M-SLEDAI scores. Musculoskeletal (MSK) involvement was independently associated with lower M-SLEQoL in physical function, activity and symptom domains. Meanwhile, MSK and NPSLE were associated with fatigue in M-LupusQoL.ConclusionBoth M-SLEQoL and M-LupusQoL are reliable and valid as disease -specific QoL instruments for Malaysian patients. The M-Lupus QoL has better discriminative validity compared to the M-SLEQoL. SLE patients with MSK involvement are at risk of poor QoL in multiple domains including physical function, activity, symptoms and fatigue.
Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data
Authors: Vatazin A. V. , Parshina E. V. , Kantaria R. O. , Stepanov V. A. , Zulkarnaev A. B. 
Published: May 2023

BACKGROUND: There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia.AIM: to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy.METHOD: This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured.RESULTS: Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018).CONCLUSION: The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.
Gonadotropin-dependent precocious puberty: genetic and clinical characteristics
Authors: Khabibullina D. A. , Kolodkina A. A. , Vizerov T. V. , Zubkova N. A. , Bezlepkina O. B. 
Published: May 2023

BACKGROUND: In 90% cases of girls and 25–60% cases of boys the cause of gonadotropin-dependent precocious puberty (PP) is unclear. Up to 25–27.5% of gonadotropin-dependent PP cases are monogenic and suggest autosomal-dominant inheritance with incomplete sex-dependent penetrance. To date, mutations in genes KISS1, KISS1R, MKRN3, DLK1 have been described as causal variants leading to precocious hypothalamic-pituitary axis activation in childhood. Genetic testing in patients with hereditary forms of PP can expand our knowledge of underlying molecular mechanisms of the disease and it is also necessary for genetic counselling.AIM: To study clinical features and genetic characteristics of patients with idiopathic gonadotropin-dependent precocious puberty.MATERIALS AND METHODS: A group of patients with idiopathic gonadotropin-dependent precocious puberty and positive family history (early or precocious puberty) was examined. Laboratory and instrumental diagnostic tests, full-exome sequencing (NGS, next-generation sequencing) were provided for all patients.RESULTS: The study included 30 patients (29 girls, 1 boy) with idiopathic gonadotropin-dependent precocious puberty. The median of patients age at the time of the examination was 7,2 years [6,5; 7,7]. Positive family history presented in all cases: in 40% of patients on father’s side, in 37% — on mother’s side, in 23% of patients PP was diagnosed in siblings. The fullexome sequencing was conducted to 21 patients: in 61,9% of cases (95% CI [40;79]) nucleotide variants were identified in genes, associated with gonadotropin-dependent precocious puberty. MKRN3 gene defect was detected in most cases (77% cases (95% CI [49; 92]), which consistent with international data on its highest prevalence in the monogenic forms of PP. In 23% of cases (95% CI [7; 50]) nucleotide variants were identified in other candidate genes associated with neuroontogenesis and neuroendocrine regulation mechanisms of hypothalamic-pituitary axis.CONCLUSION: Our study confirms that detailed family history data in children with PP provides a rational approach to molecular-genetic testing. Data of inheritance pattern and clinical manifestations will simplify the diagnosis of hereditary forms of disease and enhance genetic counselling of families, followed by timely examination and administration of pathogenetic therapy.
Olfactory function and olfactory bulbs in patients with Kallmann syndrome
Authors: Kokoreva K. D. , Chugunov I. S. , Vladimirova V. P. , Ivannikova T. E. , Bogdanov V. P. , Bezlepkina O. B. 
Published: May 2023

BACKGROUND: The majority of Kallmann patients have anosmia or hyposmia. This is how the disease is diagnosed. Some of them don’t have such complaints but olfactory dysfunction is diagnosed via olfactometry. Nowadays there is the lack of information about correlation between olfactometry results and subjective complaints. Correlation between olfactory bulbs size and olfactory dysfunction has been little studied.AIM: To explore olfactory bulb size and olfactory function in patients with congenital isolated hypogonadotropic hypogonadism. To correlate olfactory bulb sizes and smell test scores.MATERIALS AND METHODS: Single-centre comparative study. 34 patients were included. The main group consisted of 19 patients with hypogonadotropic (15 –with Kallmann syndrome, 4 — with normosmic hypogonadism). Olfactory bulbs MRI were provided to all the patients, olfactory test (Sniffin’ Sticks Test) and molecular-genetic studies were provided in all patients with hypogonadism. Control group consisted of 15 patients who were provided with orbits MRI. Olfactory bulbs were evaluated additionally in them.RESULTS: Normal size of olfactory bulbs were only in 1 patient with hypogonadism. Olfactory bulbs height and width were significantly smaller in patients with hypogonadism in comparison with control group (p<0.01). Height median of right bulb was 1.0 mm [0.2; 1.8] in patients from the main group vs. 3.0 [2.5; 3.2] in controls, width median of right bulb was 1.0 mm [0.2; 1.9] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Height median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 3.0 [2.7; 3.2] in controls, width median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Correlation has been established between left bulb height (r=0.59) and width (r=0.67) and olfactometry results (p<0.05). 4 patients had no anosmia complaints but had olfactory dysfunction according to Sniffin’ Sticks Tests.CONCLUSION: Olfactometry was able to diagnose olfactory dysfunction in 78.5% (i.e. in 15 out of 19 patients with congenital isolated hypogonadotropic hypogonadism. However, anosmia complaints had only 11 out of 19 patients. It is the first results of olfactory bulb sizes in patients with hypogonadotropic hypogonadism in Russia. Uni — or bilateral hypoor aplasia were diagnosed in 94.7% patients with hypogonadism regardless of olfactory dysfunction. Bilateral olfactory bulbs hypoplasia were the most common MRI-finding (36.8%). Unilateral hypoor aplasia was diagnosed in 31.6% patients.