bluuebunny/crossref_metadata_2025_split huggingface dataset:
AL amyloidosis: untangling new therapies
Authors: Bal Susan , Landau Heather 
Published: December 2021

Abstract
Systemic light chain (AL) amyloidosis is a protein misfolding disorder characterized by the deposition of abnormal immunoglobulin light chains in fibrillary aggregates, resulting in end-organ damage. Several unique challenges face treating physicians, including delayed diagnosis, advanced vital organ involvement, and morbidity with treatment. Aggressive supportive care and risk-adapted application of plasma cell–directed therapies are the cornerstones of management. The therapeutic revolution in multiple myeloma will likely further expand the arsenal against plasma cells. Careful investigation of these agents will be critical to establish their role in this fragile population. The promise of fibril-directed therapies to restore organ function remains despite early disappointments. In this review, we discuss new therapies to tackle AL amyloidosis using a case-based approach.
Diamond-Blackfan anemia
Authors: Da Costa Lydie M. , Marie Isabelle , Leblanc Thierry M. 
Published: December 2021

AbstractDiamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome, characterized as a rare congenital bone marrow erythroid hypoplasia (OMIM#105650). Erythroid defect in DBA results in erythroblastopenia in bone marrow as a consequence of maturation blockade between the burst forming unit–erythroid and colony forming unit–erythroid developmental stages, leading to moderate to severe usually macrocytic aregenerative (&lt;20 × 109/L of reticulocytes) anemia. Congenital malformations localized mostly in the cephalic area and in the extremities (thumbs), as well as short stature and cardiac and urogenital tract abnormalities, are a feature of 50% of the DBA-affected patients. A significant increased risk for malignancy has been reported. DBA is due to a defect in the ribosomal RNA (rRNA) maturation as a consequence of a heterozygous mutation in 1 of the 20 ribosomal protein genes. Besides classical DBA, some DBA-like diseases have been identified. The relation between the defect in rRNA maturation and the erythroid defect in DBA has yet to be fully defined. However, recent studies have identified a role for GATA1 either due to a specific defect in its translation or due to its defective regulation by its chaperone HSP70. In addition, excess free heme-induced reactive oxygen species and apoptosis have been implicated in the DBA erythroid phenotype. Current treatment options are either regular transfusions with appropriate iron chelation or treatment with corticosteroids starting at 1 year of age. The only curative treatment for the anemia of DBA to date is bone marrow transplantation. Use of gene therapy as a therapeutic strategy is currently being explored.
Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer
Authors: Zheng Yang , Tang Lili , Liu Ziling 
Published: December 2021

Abstract
Background
Inhibitors targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have prolonged survival in small groups of non-small cell lung cancer (NSCLC) patients, but biomarkers predictive of the response to the immune checkpoint inhibitors (ICIs) remain rare.

Methods
The nonnegative matrix factorization (NMF) was performed for TCGA-NSCLC tumor samples based on the LM22 immune signature to construct subgroups. Characterization of NMF subgroups involved the single sample gene set variation analysis (ssGSVA), and mutation/copy number alteration and methylation analyses. Construction of RNA interaction network was based on the identification of differentially expressed RNAs (DERs). The prognostic predictor was constructed by a LASSO-Cox regression model. Four GEO datasets were used for the validation analysis.

Results
Four immune based NMF subgroups among NSCLC patients were identified. Genetic and epigenetic analyses between subgroups revealed an important role of somatic copy number alterations in determining the immune checkpoint expression on specific immune cells. Seven hub genes were recognized in the regulatory network closely related to the immune phenotype, and a three-gene prognosis predictor was constructed.

Conclusions
Our study established an immune-based prognosis predictor, which might have the potential to select subgroups benefiting from the ICI treatment, for NSCLC patients using publicly available databases.
Video display terminal use and other risk factors for abnormal blinking in children: gender differences
Authors: Zhao Hui , Wu Shi-Nan , Zhang Qi , Zhao Chen , Shu Hui-Ye , Ge Qian-Min , Shao Yi 
Published: December 2021

Abstract
Objective
To explore the risk factors for abnormal blinking in children and compare these between boys and girls.

Methods
Children attending the Children's Optometry Clinic between June 2019 and June 2020 were recruited for the study. The time they had spent viewing video displays (VDTt) over the past 6 months was recorded. Incomplete blinking (IB) and blinking rate were measured and all participants were allocated to groups based on their blink rate (<20 times/min = normal blinking group, NBG; ≥20 times/min = abnormal blinking group, ABG). Tear film (TF) stability was also evaluated. The corresponding statistical methods are used to analyze the data.

Results
A total of 87 boys and 80 girls were enrolled in the study. No significant difference in age was found between the 2 groups. There was a significant difference in TF stability between the two groups (P<0.05). According to binary logistic analysis, VDTt and ocular protection index (OPI) are important risk factors for abnormal blinking, with cut-off values of 1.75 hours and 1.014 respectively in boys; and 1.25 hours and 1.770 respectively in girls. The average of lipid layer thickness was an important protective factor for children using VDT for long periods, with a cut-off value of 58.5 nm in boys and 53.5nm in girls.

Conclusion
Risk factors for abnormal blinking in both boys and girls include VDTt and OPI.
RPE disruption and hyper-transmission are early signs of secondary CNV with punctate inner choroidopathy in structure-OCT
Authors: Chen Yanru , Chen Qian , Li Xiaoxin , Li Minghan 
Published: December 2021

Abstract
Purpose
To study whether retinal pigment epithelium (RPE) disruption and choroidal hyper-transmission on spectral-domain optical coherence tomography (SD-OCT) are signs of inflammatory neovascularization (CNV) in punctate inner choroidopathy (PIC).

Methods
This is a prospective cohort study. Seventeen patients (18 eyes) were diagnosed as PIC without CNV at baseline. Changes of morphological characteristics including choroidal hyper-transmission, hypo-transmission, RPE disruption, and ellipsoid zone (EZ) damage on SD-OCT were observed and recorded at baseline, 4, 8 and 12 weeks, respectively. The occurrence of CNV was detected by OCTA at each visit. Fisher’s exact test was used to compare the relationship with each morphological sign and evaluate the predictable capability of secondary CNV in PIC (PIC+CNV) based on the structure changes on OCT.

Results
Among the 18 eyes, a total of 5 eyes (27.8%) developed PIC+CNV subsequently within 4 weeks follow-up. At 4, 8 and 12 weeks of follow-up, RPE disruption and choroidal hyper-transmission were found in all 5 PIC+CNV eyes. The incidence of RPE disruption was significant higher in PIC+CNV eyes compared with PIC eyes (P=0.001). PIC eyes with hyper-transmission had a higher risk for developing CNV compared with those without hyper-transmission (P=1.17×10-3). 2 out of 5 PIC+CNV eyes had a choroidal hypo-transmission component adjacent to hyper-transmission zone at 4 weeks of follow-up, and hypo-transmission could be observed in all 5 PIC+CNV eyes at 8 weeks of follow-up. The incidence of choroidal hypo-transmission was significant higher in PIC+CNV eyes than PIC eyes after 8 weeks. EZ damage began to recover at 4 weeks of follow-up and had no significant difference in the PIC eyes and PIC+CNV eyes (P=0.150, 0.196, 0.353).

Conclusion
The presence of choroidal hyper-transmission and RPE disruption on SD-OCT is associated with the PIC+CNV. SD-OCT imaging facilitates the differentiation and track of the progression of inflammatory lesions and secondary CNV in PIC.
Long-term effectiveness of behavioural intervention in preschool children with attention deficit hyperactivity disorder in Southeast China – a randomized controlled trial
Authors: Huang Xin-xin , Ou Ping , Qian Qin-fang , Huang Yan 
Published: December 2021

Abstract
Background
Attention-deficit hyperactivity disorder (ADHD) is the most common behavioral disorder. Behavioural intervention in preschool children with ADHD is considered effective. This study discussed the long-term effectiveness of behavioural intervention in the context of nondrug therapy.

Methods
The study was a prospective, randomised controlled trial in which 201 preschoolers diagnosed with ADHD who were not receiving any treatment were assigned to two groups from January 2018 to May 2019, 101 were assigned to the conventional group and 100 to the behavioural intervention group. The behavioural intervention group included parental training, behavioural therapy, attention training, relief therapy and game therapy, in addition to the conventional group offerings. Children were evaluated at a baseline, at the end of the 12-month intervention and six months after the intervention. The primary and secondary outcome variables included attention time, the impulse-hyperactivity and hyperactivity index from Conners parent symptom questionnaire (PSQ), full-scale attention quotient (FAQ) and full-scale response control quotient (FRCQ) from integrated visual and auditory comprehensive continuous performance tests. The attention time was observed and recorded by parents, and others were performe(PSQ)d by physicians in the clinic. All statistical analyses were conducted using SPSS V26.0 (IBM), including the descriptive statistics and mixed-effects models and so on.

Results
The participants’ mean age was (66.17±9.00) months in the behavioural group and (67.54±6.22) months in the conventional group .A total of 190 participants completed a follow-up six months after the intervention. The attention time, Conners parent symptom questionnaire (PSQ), full-scale attention quotient (FAQ) and full-scale response control quotient (FRCQ) increased significantly over time, and the behavioural group improvements were higher than those of conventional group. There was a significant main effect of time (pretest/posttest/follow-up) and group on all outcome measures (t =-12.549-4.069, p<0.05), and a significant interaction of time and group on attention time, impulsivity/hyperactivity, FAQ and FRCQ (t =-3.600-3.313, p<0.05).

Conclusion
Behavioural intervention can effectively improve behaviour management and relieve symptoms in children with ADHD. These effects lasted at least six months. This study provides a promising approach for improving clinical efficacy with preschool children with ADHD.
Rapid identification of pathogens associated with ventilator-associated pneumonia by Nanopore sequencing
Authors: Wu Nan , Ranjan Piyush , Tao Changyu , Liu Chao , Yang Ence , He Bei , Erb-Downward John R. , Bo Shining , Zheng Jiajia , Guo Chenxia , Liu Beibei , Sun Lina , Yan Wei , Wang Meng , Wang Wenting , Wen Jianing , Yang Ping , Yang Lin , Tian Qiaoshan , Dickson Robert P. , Shen Ning 
Published: December 2021

Abstract
Background
Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens.

Methods
The endotracheal aspirate (ETA) of 83 patients with suspected VAP from Peking University Third Hospital (PUTH) was collected, saponins were used to deplete host genomes, and PCR- or non-PCR-amplified library construction methods were used and compared. Sequence was performed with MinION equipment and local data analysis methods were used for sequencing and data analysis.

Results
Saponin depletion effectively removed 11 of 12 human genomes, while most pathogenic bacterial genome results showed no significant difference except for S. pneumoniae. Moreover, the average sequence time decreased from 19.6 h to 3.62 h. The non-PCR amplification method and PCR amplification method for library build has a similar average sensitivity (85.8% vs. 86.35%), but the non-PCR amplification method has a better average specificity (100% VS 91.15%), and required less time. The whole method takes 5–6 h from ETA extraction to pathogen classification. After analysing the 7 pathogens enrolled in our study, the average sensitivity of metagenomic sequencing was approximately 2.4 times higher than that of clinical culture (89.15% vs. 37.77%), and the average specificity was 98.8%.

Conclusions
Using saponins to remove the human genome and a non-PCR amplification method to build libraries can be used for the identification of pathogens in the ETA of VAP patients within 6 h by MinION, which provides a new approach for the rapid identification of pathogens in clinical departments.
Analysis of maturation dynamics and developmental competence of in vitro matured oocytes under time-lapse monitoring
Authors: Yang Qiyu , Zhu Lixia , Wang Meng , Huang Bo , Li Zhou , Hu Juan , Xi Qingsong , Liu Jing , Jin Lei 
Published: December 2021

Abstract
Background
To improve the developmental competence of in vitro cultured oocytes, extensive literature focused on maturation rate improvement with different additives in culture medium, while studies investigating the maturation dynamics of oocytes during in vitro maturation (IVM) and the influencing factors on oocyte viability are scarce.

Methods
The study involved a retrospective observation by time-lapse monitoring of the IVM process of 157 donated GV oocytes from 59 infertile couples receiving ICSI in 2019, in Tongji Hospital, Wuhan, China. The GV oocytes derived from controlled ovarian hyperstimulation (COH) cycles underwent rescue IVM (R-IVM), and the maturation dynamics, including GVBD time (GV-MI), time from GVBD to maturation (MI-MII), maturation time (GV-MII), and MII arrest duration (MII-ICSI), were recorded by time-lapse monitoring. The matured oocytes were inseminated at different MII arrest points and subsequent embryo developments were assessed. The effects of baseline clinical characteristics, oocyte diameters, and maturation dynamics on the developmental competence of the oocytes were also analyzed.

Results
Totally, 157 GV oocytes were collected. GVBD happened in 111 oocytes, with a median GV-MI duration of 3.7 h. The median MI-MII duration was 15.6 h and the median GV-MII duration was 19.5 h. The maturation rate reached 56.7% at 24 h and 66.9% at 48 h, and the clinical factors, including patient age, FSH level, AMH level, ovarian stimulation protocol, and serum estradiol and progesterone levels on hCG trigger day, showed no effects on the 24-h maturation rate. The normal fertilization rate of oocytes resuming meiosis within 8 h and matured within 24 h was significantly higher than that of oocytes resuming meiosis after 8 h and matured after 24 h. Furthermore, among those oocytes matured within 24 h, the high-quality embryo formation rate of oocytes resuming meiosis within 4.5 h and matured within 19 h was significantly higher. All stated time was measured from the start point of IVM. Additionally, for oocytes from patients with serum progesterone levels less than 1 ng/ml on hCG trigger day, the high-quality embryo formation rate was significantly increased.

Conclusion
R-IVM technology could increase the available embryos for patients in routine COH cycles, but excessive culture beyond 24 h is not recommended. GV-MI duration of the oocyte, recorded by time-lapse system, and serum progesterone levels of patients on hCG trigger day can significantly affect the developmental potential of the IVM oocytes.
RE: [No Subject]—On Nonbinary Gender
Authors: Bey Marquis 
Published: December 2021

Abstract
This essay attempts to imagine what nonbinary gender might be through an autotheoretical and imaginative email exchange between the author, as “X,” and the author’s gender as nonbinary. Indeed, theorized conversationally throughout are the difficulties and potentialities of nonbinary gender, or nonbinariness as a refusal of gender.
The use of digital magnification to reduce radiation dose in the cardiac catheter laboratory
Authors: Dalvi Shailesh , Roberts Hywel Mortimer , Bellamy Christopher , Rees Michael 
Published: December 2021

Objectives:
To audit whether using magnification of images by use of a large viewing screen using digital matrix magnification which enlarges the image by 33% without using the X-ray machine zoom magnification protocols on a Siemens Artis Zee X-ray machine in a cardiac catheter laboratory results in a reduction of kerma–area product (KAP) for both diagnostic and interventional procedures. This reduction was predicted in an in vitro study in our laboratory, which has previously shown a 20.4% reduction in KAP.

Methods:
A retrospective analysis was conducted of the radiation exposure to compare the measured KAP recorded during the period when conventional magnification with automatic brightness and dose control was used on a Siemens Artis Zee X-ray machine with a flat panel detector and when magnification settings were avoided by using a large screen to enlarge and project a non-magnified image by digital magnification. The analysis was carried out for patients having a diagnostic coronary angiogram and those having an interventional coronary procedure.

Results:
For diagnostic coronary angiograms the median KAP per procedure in the period using conventional magnification was 2124.5 µGy.m2 compared to 1401 µGy.m2 when image matrix magnification was used, a 34% reduction (p &lt; 0.0001). For interventional coronary procedures, the median KAP per procedure in the period using conventional magnification was 3791 µGy.m2 compared to 2568.5 µGy.m2 when image matrix magnification was used, a 32% reduction (p &lt; 0.0001).

Conclusion:
Avoiding using conventional magnification in the cardiac catheter laboratory and using a large screen to magnify images was associated with a statistically significant greater than 30% reduction in KAP.

Advances in knowledge:
This paper is the proof in clinical practice of a theoretical conclusion that radiation dose (KAP) is reduced by use of Image matrix magnification using a large viewing screen without the need to use X-ray tube magnification without significant loss of image resolution in interventional cardiology. The same approach will be useful in interventional radiology.
Multisystem inflammatory syndrome in children associated with SARS-CoV-2: extracardiac radiological findings
Authors: Ucan Berna , Kaynak Sahap Seda , Cinar Hasibe Gokce , Tasci Yildiz Yasemin , Uner Cigdem , Polat Meltem , Derinkuyu Betul Emine 
Published: December 2021

Objective:
Multisystem inflammatory syndrome in children (MIS-C) is seen as a serious delayed complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this study was to describe the most common imaging features of MIS-C associated with SARS-CoV-2.

Methods:
A retrospective review was made of the medical records and radiological imaging studies of 47 children (26 male, 21 female) in the age range of 25 months–15 years who were diagnosed with MIS-C between August 2020 and March 2021. Chest radiographs were available for all 47 patients, thorax ultrasound for 6, chest CT for 4, abdominal ultrasound for 42, abdomen CT for 9, neck ultrasound for 4, neck CT for 2, brain CT for 1, and brain MRI for 3.

Results:
The most common finding on chest radiographs was perihilar–peribronchial thickening (46%). The most common findings on abdominal ultrasonography were mesenteric inflammation (42%), and hepatosplenomegaly (38%, 28%). Lymphadenopathy was determined in four patients who underwent neck ultrasound, one of whom had deep neck infection on CT. One patient had restricted diffusion and T2 hyperintensity involving the corpus callosum splenium on brain MRI, and one patient had epididymitis related with MIS-C.

Conclusion:
Pulmonary manifestations are uncommon in MIS-C. In the abdominal imaging, mesenteric inflammation, hepatosplenomegaly, periportal edema, ascites and bowel wall thickening are the most common findings.

Advances in knowledge:
The imaging findings of MIS-C are non-specific and can mimic many other pathologies. Radiologists should be aware that these findings may indicate the correct diagnosis of MIS-C.
Tarsal tunnel syndrome: current rationale, indications and results
Authors: Rodríguez-Merchán E. Carlos , Moracia-Ochagavía Inmaculada 
Published: December 2021

Tarsal tunnel syndrome (TTS) is a neuropathy due to compression of the posterior tibial nerve and its branches.It is usually underdiagnosed and its aetiology is very diverse. In 20% of cases it is idiopathic.There is no test that diagnoses it with certainty. The diagnosis is usually made by correlating clinical history, imaging tests, nerve conduction studies (NCSs) and electromyography (EMG).A differential diagnosis should be made with plantar fasciitis, lumbosacral radiculopathy (especially S1 radiculopathy), rheumatologic diseases, metatarsal stress fractures and Morton’s neuroma.Conservative management usually gives good results. It includes activity modification, administration of pain relief drugs, physical and rehabilitation medicine, and corticosteroid injections into the tarsal tunnel (to reduce oedema).Abnormally slow nerve conduction through the posterior tibial nerve usually predicts failure of conservative treatment.Indications for surgical treatment are failure of conservative treatment and clear identification of the cause of the entrapment. In these circumstances, the results are usually satisfactory. Surgical success rates vary from 44% to 96%.Surgical treatment involves releasing the flexor retinaculum from its proximal attachment near the medial malleolus down to the sustentaculum tali. Ultrasound-guided tarsal tunnel release is possible.A positive Tinel’s sign before surgery is a strong predictor of surgical relief after decompression.Surgical treatment achieves the best results in young patients, those with a clear aetiology, a positive Tinel’s sign prior to surgery, a short history of symptoms, an early diagnosis and no previous ankle pathology.Cite this article:EFORT Open Rev2021;6:1140-1147. DOI: 10.1302/2058-5241.6.210031