bluuebunny/crossref_metadata_2025 huggingface dataset:
Insurance payment for artificial intelligence technology: Methods used by a stroke artificial intelligence system and strategies to qualify for the new technology add-on payment
Authors: Murray Nick M , Phan Phillip , Hager Greg , Menard Andrew , Chin David , Liu Alvin , Hui Ferdinand K
Published: January 2022

The first ever insurance reimbursement for an artificial intelligence (AI) system, which expedites triage of acute stroke, occurred in 2020 when the Centers for Medicare and Medicaid Services (CMS) granted approval for a New Technology Add-on Payment (NTAP). Key aspects of the AI system that led to its approval by the CMS included its unique mechanism of action, use of robotic process automation, and clear linkage of the system’s output to clinical outcomes. The specific strategies employed encompass a first-case scenario of proving reimbursable value for improved stroke outcomes using AI. Given the rapid change in utilization of AI technology in stroke care, we describe the economic drivers of stroke AI systems in healthcare, focusing on concepts of reimbursement for value added by AI to the stroke care system. This report reviews (1) the successful approach used by the first NTAP-approved AI system, (2) economic variables in insurance reimbursement for AI, and (3) resultant strategies that may be utilized to facilitate qualification for NTAP reimbursement, which may be adopted by other AI systems used in stroke care.
Dynamic mechanical properties of hybrid fiber reinforced concrete
Authors: Zhang Yong , Chen Li , Zhou Dong-lei
Published: January 2022

In this study, the dynamic mechanical properties of hybrid fiber reinforced concrete (HFRC) are analyzed with respect to failure mode, dynamic increase factor (DIF), and peak strain by means of a SHPB testing apparatus. The factors that influence the dynamic mechanical properties include fiber type and fiber content. It is concluded that the best dynamic mechanical properties of fibers are CS-PHFRC at medium and low strain rates and AS-PHFRC at a high strain rate. Within a certain range, the higher the fiber content is, the larger the DIF of the corresponding HFRC and the more obvious the increase in dynamic compressive strength. AS-CSHFRC improves the dynamic compressive deformability of the HFRC. The polypropylene fiber causes plasticity, as shown in the failure mode of concrete. The Ottosen nonlinear elastic model, modified by introducing the damage factor, can better describe the dynamic mechanical properties of HFRC.
Distal ureteral atresia – an embryological dilemma
Authors: Kattepura Subramanya , Shubha Attibele Mahadevaiah , Das Kanishka
Published: January 2022

Introduction:

Distal ureteral atresia is a rare urinary tract anomaly generally associated with ipsilateral renal dysplasia and abnormalities such as multicystic dysplastic kidney, hydronephrosis and megaureter in the contralateral kidney. Despite burgeoning investigation modalities, definitive preoperative diagnosis of this condition is rarely feasible, also the embryological disarray of events that result in the development of this anomaly and the associated malformations is not clearly understood.

Case presentation:

We hereby report two cases of distal ureteral atresia and discuss the diversity in their presentations, diagnosis, atypical associations and management and review the possible embryological mal-development.

Conclusion:

Distal ureteral atresia with urogenital sinus as in Case 1 has not been documented so far and a plausible embryological explanation is deduced regarding its occurrence. The course of the affected kidney following timely and adequate relief of obstruction in Case 2 is depicted, highlighting the eventual management.

Level of evidence:

Not applicable
A single centre service evaluation of the pre-biopsy mpMRI pathway for prostate cancer diagnosis
Authors: Kong Mark , Lee Louise , Mulcahy Kevin , Rajesh Arumugam
Published: January 2022

Aim:

To study the efficacy and impact of the local pre-biopsy multiparametric magnetic resonance imaging (mpMRI) pathway for prostate cancer diagnosis.

Methods:

In this tertiary centre, 570 patients had prostate mpMRI across a 6-month period in 2019. A total of 511 patients met inclusion criteria for retrospective analysis. MRI reporting used the Prostate Imaging-Reporting and Data System (PI-RADS) v2.1. These were assessed alongside histological outcomes and diagnostic times. PI-RADS ⩾ 3 were recommended for biopsy consideration. Gleason scoring ⩾ 3 + 4 and 3 + 3 were used to define clinically and non-clinically significant prostate cancer (csPCa and nsPCa), respectively.

Results:

Overall prostate cancer prevalence was 40% (204/511, csPCa in 31.1%) with an overall biopsy avoidance of 32.1% (164/511). Around 69.7% (356/511) scored PI-RADS ⩾ 3 and 30.3% (155/511) scored PI-RADS 1–2. About 22.6% (35/155) of PI-RADS 1–2 patients proceeded to biopsy, demonstrating a negative predictive value of 91.43% for csPCa. For PI-RADS ⩾ 3 patients, 63.4% (197/312) of those biopsied had cancer (Gleason ⩾ 3 + 3), with 50% (156/312) demonstrating csPCa. Around 76.7% (102/133) of PI-RADS 5, 35.3% (48/136) of PI-RADS 4, 14.0% (6/43) of PI-RADS 3 and 8.6% (3/35) of PI-RADS 1–2 scores demonstrated csPCa. Overall median prostate-specific antigen (PSA) density was 0.15 ng/mL2 (IQR: 0.10–0.27/mL2). PSA density were significantly different across PI-RADS cohorts ( H = 118.8, p < 0.0001) and across all three biopsy outcomes ( H = 99.72, p < 0.0001). Only 34.3% (119/347) of biopsied patients met the NHS 28-day standard. MRI acquisition and reporting met the 14-day local standard in 96.1% (491/511). The biopsy was the most delayed component with a median of 20 days (IQR: 8–43).

Conclusion:

Pre-biopsy mpMRI with PI-RADS scoring safely avoided biopsy in almost one-third (32.1%) of patients. The use of PSA-density in risk stratifying PI-RADS 3 lesions has informed local practice in the period 2020–2021, with implementation of a PSA-density threshold of 0.12 ng/mL2. Biopsy scheduling issues and anaesthetic requirements need to be overcome to improve diagnostic waiting times.

Level of evidence:

2
MRI-based nomogram for the prediction of prostate cancer diagnosis: A multi-centre validated patient–physician decision tool
Authors: Chau Edwin M , Russell Beth , Santaolalla Aida , Van Hemelrijck Mieke , McCracken Stuart , Page Toby , Liyanage Sidath H , Aning Jonathan , Gnanapragasam Vincent J , Acher Peter
Published: January 2022

Objective:

To update and externally validate a magnetic resonance imaging (MRI)-based nomogram for predicting prostate biopsy outcomes with a multi-centre cohort.

Materials and methods:

Prospective data from five UK-based centres were analysed. All men were biopsy naïve. Those with missing data, no MRI, or prostate-specific antigen (PSA) > 30 ng/mL were excluded. Logistic regression analysis was used to confirm predictors of prostate cancer outcomes including MRI-PIRADS (Prostate Imaging Reporting and Data System) score, PSA density, and age. Clinically significant disease was defined as International Society of Urological Pathology (ISUP) Grade Group ⩾ 2 (Gleason grade ⩾ 7). Biopsy strategy included transrectal and transperineal approaches. Nomograms were produced using logistic regression analysis results.

Results:

A total of 506 men were included in the analysis with median age 66 (interquartile range (IQR) = 60–69). Median PSA was 6.6 ng/mL (IQR = 4.72–9.26). PIRADS ⩾ 3 was reported in 387 (76.4%). Grade Group ⩾ 2 detection was 227 (44.9%) and 318 (62.8%) for any cancer. Performance of the MRI-based nomogram was an area under curve (AUC) of 0.84 (95% confidence interval (CI) = 0.81–0.88) for Grade Group ⩾ 2% and 0.85 (95% CI = 0.82–0.88) for any prostate cancer.

Conclusion:

We present external validation of a novel MRI-based nomogram in a multi-centre UK-based cohort, showing good discrimination in identifying men at high risk of having clinically significant disease. These findings support this risk calculator use in the prostate biopsy decision-making process.

Level of evidence:

2c
Testicular metastasis in prostate cancer: A rare case of testicular metastasis diagnosed with 68Ga-PSMA and review of the literature
Authors: Ozyigit Gokhan , Akdogan Bulent , Yilmaz Melek Tugce , Guner Gunes , Bozkurt Murat Fani
Published: January 2022

Objective:

Testicular metastasis in prostate cancer is a rare entity. We aimed to report the case where this rare condition was diagnosed with Gallium prostate-specific membrane antigen–positron emission tomography/computed tomography (68Ga-PSMA-PET/CT).

Subjects/patients and methods:

A 68-year-old male with a prostate adenocarcinoma presented with testicular metastasis. The patient was diagnosed with 68Ga-PSMA-PET/CT, and bilateral inguinal orchiectomy was performed. Herein, our case is presented, and a short review of the literature is carried out.

Conclusion:

68Ga-PSMA-PET/CT is an effective imaging method for detecting rare metastases.

Level of evidence:

4
Real-world effectiveness of dimethyl fumarate versus fingolimod in a cohort of patients with multiple sclerosis using standardized, quantitative outcome metrics
Authors: Hersh Carrie M , Altincatal Arman , Belviso Nicholas , Kapadia Shivani , de Moor Carl , Rudick Richard , Williams James Rhys , Miller Catherine , Koulinska Irene
Published: January 2022

Background

Prior studies suggest comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapse, Expanded Disability Status Scale (EDSS), and magnetic resonance imaging (MRI) lesion metrics.

Objective

Compare the real-world effectiveness of DMF versus FTY using quantitative, validated neuroperformance tests, MRI, and serum neurofilament light chain (sNfL) outcomes while controlling for between-group differences.

Methods

Patients were eligible if on DMF or FTY when first enrolled in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network and had ≥1-year follow-up in MS PATHS. Sensitivity analysis included a subgroup who started DMF/FTY ≤2 years from enrolment. After propensity score weighting, differences in means and in mean 1-year change of neuroperformance and MRI outcomes were compared. sNfL levels were assessed. This was a non-randomized comparison.

Results

In the overall cohort, no significant differences were observed between DMF ( n = 702) and FTY ( n = 600) in neuroperformance or MRI outcomes including brain volume loss; mean time (SD) since treatment initiation was 1.98 (0.68) years for DMF and 2.02 (0.75) years for FTY. A sensitivity analysis controlling for DMF and FTY treatment duration yielded similar results.

Conclusion

In this study, DMF and FTY demonstrated similar effects on physical and cognitive neuroperformance and MRI outcomes. Direct comparisons to other fumarates and S1P receptor modulators were not conducted.
Talus Visualization in Ankle Fractures: How Much Are We Really Seeing?
Authors: Hinckley Nathaniel B. , Hassebrock Jeffrey D. , Karsen Phillip J. , Deckey David G. , Fernandez Andrea , Kile Todd A. , Drakos Mark C. , Patel Karan A.
Published: January 2022

Background:

Despite appropriate care, a subset of patients with ankle fractures has persistent pain. This condition may be associated with intra-articular pathology, which is present up to 65% of the time.

Purpose:

To quantify how much of the talus is visible through an open approach to a standard supination external rotation bimalleolar ankle fracture as a percentage of the entire weightbearing surface of the talus.

Study Design:

Descriptive laboratory study.

Methods:

Standard ankle approaches to lateral and medial malleolar fractures were performed in 4 cadaveric ankles from 2 cadavers. Osteotomies were made to simulate a supination external rotation bimalleolar ankle fracture based on the Lauge-Hansen classification. The visible segments of talar cartilage were removed. The tali were then exhumed, and the entire weightbearing superior portion of the talus was assessed and compared with the amount of cartilage removed by an open approach. The mean of the data points as well as the 95% confidence interval were calculated.

Results:

Four ankle specimens from 2 cadavers were used for these measurements. The mean surface area of the talus was 14.0 cm2 (95% CI, 13.3-14.7 cm2), while the mean area visible via an open approach was 2.1 cm2 (95% CI, 0.5-3.6 cm2). The mean proportion of the talus visualized via an open approach was 14.8% (95% CI, 3.6-26.1%).

Conclusion:

These findings indicate that the true area of weightbearing talar surface visible during an open exposure may be less than what many surgeons postulate.

Clinical Relevance:

Only a small fracture of the talus is visible via an open approach to the talus during fracture fixation. This could warrant arthroscopic evaluation of these injuries to evaluate and treat osteocondral lesions resulting from ankle fractures.
Tenecteplase versus alteplase for large vessel occlusion recanalization (T-FLAVOR): Trial protocol
Authors: Kawano Hiroyuki , Hirano Teruyuki , Inoue Manabu , Fukuda-Doi Mayumi , Iwasaki Koji , Omae Katsuhiro , Tanaka Kanta , Yamamoto Haruko , Koga Masatoshi , Sakai Nobuyuki , Nagao Takehiko , Sasaki Makoto , Hayakawa Naoki , Toyoda Kazunori
Published: January 2022

Background

Tenecteplase has higher fibrin specificity with a longer half-life and the potential to achieve higher rates of recanalization than alteplase. A critical limitation of tenecteplase is no commercial use in Japan and no experience with its administration to Japanese patients.

Hypothesis

Tenecteplase is superior to alteplase in achieving recanalization on the initial angiogram when administered ≤4.5-hour of stroke onset in patients planned for mechanical thrombectomy (MT) in Japan where alteplase at the unique dose of 0.6mg/kg is officially used.

Methods

The Tenecteplase versus alteplase For LArge Vessel Occlusion Recanalization (T-FLAVOR) trial is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, masked-endpoint, superiority study. Eligibility criteria include acute ischemic stroke with pre-stroke modified Rankin Scale score ≤3 and large vessel occlusion (internal carotid artery, middle cerebral artery, or basilar artery) eligible for intravenous thrombolysis ≤4.5-hour and MT ≤6-hour of stroke onset. After completing the safety confirmation phase involving three patients who received non-masked tenecteplase (0.25 mg/kg), 220 patients will be randomized to two groups (1:1), intravenous alteplase (0.6mg/kg, n = 110) or tenecteplase (0.25mg/kg, n = 110), prior to MT.

Outcomes

In the safety confirmation phase, the primary outcome is symptomatic intracranial hemorrhage (sICH) ≤24-36-hour. In the randomized, comparative phase, the primary efficacy outcome is substantial angiographic reperfusion (mTICI grade 2b/2c/3) or absence of retrievable thrombus on the initial angiogram. The primary safety outcome is sICH ≤24-36-hour and 90-day mortality.

Discussion

T-FLAVOR may help determine if tenecteplase should be recommended as a routine clinical strategy before MT for Japanese stroke patients.

Trial registration

jRCTs051210055
Provenance analysis of sediments in the south-east Aegean during the Upper Quaternary: a composite approach based on bulk and clay mineralogy and geochemistry
Authors: Leontopoulou Georgia , Christidis Georgios E. , Rousakis Grigorios , Müller Noémi S. , Papatheodorou George , Geraga Maria
Published: January 2022

Sediments from the ST5 deep-sea bottom core collected from the south-east Aegean Sea between Symi and Tilos islands, Greece, were examined by quantitative mineralogical analysis and geochemical analysis to infer provenance and palaeoenvironmental control over sediment deposition. The mineralogical composition comprises carbonates (mainly calcite and Mg-calcite), quartz, feldspars, serpentine, amphibole and clay minerals. Chlorite is the most abundant clay mineral, whereas smectite and illite are less abundant than in the sediments in the south-west Aegean and the Cretan Sea. Semi-quantitative analysis of clay minerals from oriented clay fractions overestimates significantly the smectite content and underestimates the abundances of illite, chlorite and kaolinite. The studied sediments are enriched in MgO, Ni and Cr, which decrease in abundance with decreasing depth, following the distribution of serpentine. By contrast, the abundances of SiO2, Al2O3, Fe2O3, Na2O and K2O increase upcore. The regional S1 sapropel horizon is enriched in V and Co and has considerably greater Ba/Al ratios than the remaining sequence. The mineralogical and geochemical relationships indicate a strong ultrabasic influence, probably from the Marmaris ophiolite in the Lycian nappes. The clay mineral distribution suggests that the smectite was mainly of volcanogenic origin, the illite was supplied by the nearby landmasses of west Anatolia and the islands of Rhodes, Tilos and Symi and the contribution from the south-east Mediterranean was limited or totally lacking. The combined use of the mineralogical and geochemical analysis of bulk sediments rather than the clay fractions is not only extremely useful in tracing sediment provenance in relatively closed basins, but it also enables a more realistic assessment of the importance of water circulation patterns on sedimentation processes in such environments.
Hydrogen diffusion mechanisms in quartz: insights from H–Li,2H–H and2H–H–Li exchange experiments
Authors: Jollands Michael C. , Tollan Peter M. E. , Baumgartner Lukas P. , Müntener Othmar
Published: January 2022

The diffusivity and diffusion mechanisms of hydrogen together with with deuterium and lithium, parallel to thecaxis of quartz, were investigated experimentally at 800°C, 0.1 GPa with the activity of H2O or2H2O ≈ 1 [2H is used throughout this work to describe deuterium rather than D, to avoid confusion with the diffusion coefficient,D]. The pH was set using mixtures of H2O (or2H2O) and HCl. Three types of experiment were conducted: (1) H-in/Li-out; (2)2H-in/H-out; and (3)2H-in/H + Li out, using three different natural quartz crystals as starting materials. Profiles of H,2H and Li were measured using Fourier-transform infrared (FTIR) spectroscopy and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). H,2H and Li are charge-compensated by Al3+replacing Si4+, or by excess O2–. The total atomic concentration of monovalent cations appears to remain constant over the duration of the experiments. The resulting diffusion profiles are different for the three experimental designs and three starting materials, and some show complex shapes inconsistent with simple diffusion. A multi-site diffusion–reaction model is developed, with the theory based on previous models that have been derived mainly on the basis of conductivity measurements. In these models, the monovalent cations move away from their charge-balancing ion then diffuse rapidly to another site. The mobility of the monovalent cations is described by both a diffusion coefficient and an equilibrium constant that enables dissociation of the immobile charge-balanced defects. This model can describe complex step-shaped profiles formed in H-in/Li-out experiments, profiles with local maxima ('humped’ profiles) in2H-in/H + Li out experiments, and error function-shaped profiles in2H-in/H-out and previously published Li-in/H-out experiments. Our data provide support for models previously proposed for quartz. Studies of the lengths and forms of diffusion profiles from such experiments provide a useful complement to assertions from conductivity experiments.
Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status
Authors: Roboz Gail J. , Ravandi Farhad , Wei Andrew H. , Dombret Hervé , Thol Felicitas , Voso Maria Teresa , Schuh Andre C. , Porkka Kimmo , La Torre Ignazia , Skikne Barry , Zhong Jianhua , Beach C. L. , Risueño Alberto , Menezes Daniel L. , Ossenkoppele Gert , Döhner Hartmut
Published: January 2022

Measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Postremission maintenance therapy that prolongs MRD negativity or converts MRD+ patients to MRD− status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged ≥55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (≥0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed oral-AZA significantly improved OS and RFS vs placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs placebo and resulted in a higher rate of conversion from MRD+ at baseline to MRD− during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negativity >6 months after treatment initiation. Although presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with oral-AZA maintenance therapy compared with placebo, independent of patients’ MRD status at baseline. Registered at clinicaltrials.gov as #NCT01757535.
Echocardiographic probability of pulmonary hypertension: a validation study
Authors: D'Alto Michele , Di Maio Marco , Romeo Emanuele , Argiento Paola , Blasi Ettore , Di Vilio Alessandro , Rea Gaetano , D'Andrea Antonello , Golino Paolo , Naeije Robert
Published: January 2022

Background

According to current guidelines, the diagnosis of pulmonary hypertension (PH) relies on echocardiographic probability followed by right heart catheterisation (RHC). How echocardiography predicts PH recently redefined by mean pulmonary arterial pressure (mPAP) >20 mmHg instead of ≥25 mmHg and pulmonary vascular disease defined by pulmonary vascular resistance (PVR) ≥3 or >2 WU has not been established.

Methods

A total of 278 patients referred for PH underwent comprehensive echocardiography followed by RHC. 15 patients (5.4%) were excluded because of insufficient quality echocardiography.

Results

With PH defined by mPAP >20 mmHg, 23 patients had no PH, 146 had pre-capillary PH and 94 had post-capillary PH. At univariate analysis, maximum tricuspid regurgitation velocity (TRV) 2.9–3.4 m·s−1, left ventricle (LV) eccentricity index >1.1, right ventricle outflow tract acceleration time (RVOT-AT) <105 ms or notching, RV/LV basal diameter >1 and pulmonary artery diameter predicted PH, whereas inferior vena cava diameter and right atrial area did not. At multivariable analysis, only TRV ≥2.9 m·s−1independently predicted PH. Additional independent prediction of PVR ≥3 WU was offered by LV eccentricity index >1.1, and RVOT-AT <105 ms and/or notching, but with no improvement of optimal combination of specificity and sensitivity or positive prediction.

Conclusions

Echocardiography as recommended in current guidelines can be used to assess the probability of redefined PH in a referral centre. However, the added value of indirect signs is modest and sufficient quality echocardiographic signals may not be recovered in some patients.
Relationships between male secondary sexual traits, physiological state and offspring viability in the three-spined stickleback
Authors: Chiara Violette , Velando Alberto , Kim Sin-Yeon
Published: January 2022

Background

Sexual signals produced by males play a central role in sexual selection, but the relationship between these traits and the quality of the bearer are often ambiguous. Secondary sexual traits may represent genetic quality of the bearer, resulting in positive relationships with physiological state, or may be costly to produce, showing trade-off with physiological state. A number of studies have explored the relationships between secondary sexual traits and other functional traits, but few have studied their fitness consequences. We studied the link between diverse physiological traits and both morphological and behavioural sexual traits and examined how their interplay influences offspring viability in the three-spined stickleback.

Results

Male sticklebacks showing nest building and courtship behaviour were smaller than those not investing in reproductive activities. There was no evidence that the expression of red nuptial colouration and the quality of courtship behaviour of males are positively related to their metabolic rates, swim ability, oxidative damage and mtDNA copy number. However, individuals showing larger red nuptial colour areas had higher levels of oxidative DNA damage in their sperm. Male courtship behaviour and aggressiveness, but not red colour area, were good predictors of offspring hatching and survival.

Conclusions

Our results suggest that, in our study population at the southern edge of the species’ distribution, sexual colouration of male sticklebacks was not a good indicator of their body state, but both courtship quality and aggressiveness during the courtship are reliable cues of their gamete quality, influencing the viability of their offspring. Thus, females that choose mates based on their courtship behaviour will have high fitness. In the study population, which represents a fast pace-of-life with high reproductive rate and short lifespan, sexual ornaments of males may not honestly signal their physiological and physical state because they invest at maximum in a single reproductive season despite high costs.
HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed abstracts
Authors: Dholakia Dhwani , Kalra Ankit , Misir Bishnu Raman , Kanga Uma , Mukerji Mitali
Published: January 2022

Extreme complexity in the Human Leukocyte Antigens (HLA) system and its nomenclature makes it difficult to interpret and integrate relevant information for HLA associations with diseases, Adverse Drug Reactions (ADR) and Transplantation. PubMed search displays ~ 146,000 studies on HLA reported from diverse locations. Currently, IPD-IMGT/HLA (Robinson et al., Nucleic Acids Research 48:D948–D955, 2019) database houses data on 28,320 HLA alleles. We developed an automated pipeline with a unified graphical user interface HLA-SPREAD that provides a structured information on SNPs, Populations, REsources, ADRs and Diseases information. Information on HLA was extracted from ~ 28 million PubMed abstracts extracted using Natural Language Processing (NLP). Python scripts were used to mine and curate information on diseases, filter false positives and categorize to 24 tree hierarchical groups and named Entity Recognition (NER) algorithms followed by semantic analysis to infer HLA association(s). This resource from 109 countries and 40 ethnic groups provides interesting insights on: markers associated with allelic/haplotypic association in autoimmune, cancer, viral and skin diseases, transplantation outcome and ADRs for hypersensitivity. Summary information on clinically relevant biomarkers related to HLA disease associations with mapped susceptible/risk alleles are readily retrievable from HLASPREAD. The resource is available at URL http://hla-spread.igib.res.in/. This resource is first of its kind that can help uncover novel patterns in HLA gene-disease associations.
Combined assembly of long and short sequencing reads improve the efficiency of exploring the soil metagenome
Authors: Xu Guoshun , Zhang Liwen , Liu Xiaoqing , Guan Feifei , Xu Yuquan , Yue Haitao , Huang Jin-Qun , Chen Jieyin , Wu Ningfeng , Tian Jian
Published: January 2022

Background

Advances in DNA sequencing technologies have transformed our capacity to perform life science research, decipher the dynamics of complex soil microbial communities and exploit them for plant disease management. However, soil is a complex conglomerate, which makes functional metagenomics studies very challenging.

Results

Metagenomes were assembled by long-read (PacBio, PB), short-read (Illumina, IL), and mixture of PB and IL (PI) sequencing of soil DNA samples were compared. Ortholog analyses and functional annotation revealed that the PI approach significantly increased the contig length of the metagenomic sequences compared to IL and enlarged the gene pool compared to PB. The PI approach also offered comparable or higher species abundance than either PB or IL alone, and showed significant advantages for studying natural product biosynthetic genes in the soil microbiomes.

Conclusion

Our results provide an effective strategy for combining long and short-read DNA sequencing data to explore and distill the maximum information out of soil metagenomics.
The lolB gene in Xanthomonas campestris pv. campestris is required for bacterial attachment, stress tolerance, and virulence
Authors: Liao Chao-Tsai , Li Chih-En , Chang Hsiao-Ching , Hsu Chien-Hui , Chiang Ying-Chuan , Hsiao Yi-Min
Published: January 2022

Background

Xanthomonas campestris pv. campestris (Xcc) is a Gram-negative bacterium that can cause black rot disease in crucifers. The lipoprotein outer membrane localization (Lol) system is involved in the lipoprotein sorting to the outer membrane. Although Xcc has a set of annotated lol genes, there is still little known about the physiological role in this phytopathogen. In this study, we aimed to characterize the role of LolB of Xcc in bacterial attachment, stress tolerance, and virulence.

Results

To characterize the role of LolB, lolB mutant was constructed and phenotypic evaluation was performed. The lolB mutant revealed reductions in bacterial attachment, extracellular enzyme production, and virulence. Mutation of lolB also resulted in reduced tolerance to a myriad of stresses, including heat and a range of membrane-perturbing agents. Trans-complementation of lolB mutant with intact lolB gene reverted these altered phenotypes to the wild-type levels. From subsequent reporter assay and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis, the expression of genes that encode the major extracellular enzymes and the stress-related proteins was reduced after lolB mutation.

Conclusions

The results in this work contribute to the functional understanding of lolB in Xanthomonas for the first time, and provide new insights into the function of lolB in bacteria.
In vitro activities of thiazolidione derivatives combined with daptomycin against clinical Enterococcus faecium strains
Authors: Chen Zhong , Xiong Yanpeng , Tang Yuanyuan , Zhao Yuxi , Chen Junwen , Zheng Jinxin , Wu Yang , Deng Qiwen , Qu Di , Yu Zhijian
Published: January 2022

Background

Previous reports have demonstrated two thiazolidione derivatives (H2-60 and H2-81) can robustly inhibit the planktonic growth and biofilm formation ofS. epidermidisandS. aureusby targeting the histidine kinase YycG.Whereas the antibacterial and anti-biofilm activity of these two thiazolidione derivatives (H2-60 and H2-81) againstEnterococcus faeciumremains elusive. Here, the pET28a-YycG recombinant plasmid were in vitro expressed inE. colicompetent cell BL21 (DE3) and induced to express YycG’ protein (conding HisKA and HATPase_c domain) by 0.5 mM IPTG and was purified by Ni – NTA agarose and then for the autophosphorylation test. Antimicrobial testing and time-killing assay were also be determined. Anti-biofilm activity of two derivatives with sub-MIC concentration towards positive biofilm producers of clinicalE. faeciumwere detected using polystyrene microtiter plate and CLSM.

Results

The MICs of H2-60 and H2-81 in the clinical isolates ofE. faeciumwere in the range from 3.125 mg/L to 25 mg/L. Moreover, either H2-60 or H2-81 showed the excellent bactericidal activity againstE. faeciumwith monotherapy or its combination with daptomycin by time-killing assay.E. faeciumplanktonic cells can be decreased by H2-60 or H2-81 for more than 3 × log10 CFU/mL after 24 h treatment when combined with daptomycin. Furthermore, over 90% ofE. faeciumbiofilm formation could markedly be inhibited by H2-60 and H2-81 at 1/4 × MIC value. In addition, the frequency of the eradicated viable cells embedded in mature biofilm were evaluated by the confocal laser microscopy, suggesting that of H2-60 combined with ampicillin or daptomycin was significantly high when compared with single treatment (78.17 and 74.48% vs. 41.59%, respectively,P < 0.01).

Conclusion

These two thiazolidione derivatives (H2-60 and H2-81) could directly impact the kinase phosphoration activity of YycG ofE. faecium. H2-60 combined with daptomycin exhibit the excellent antibacterial and anti-biofilm activity againstE. faeciumby targeting YycG.
Geo–economic variations in epidemiology, ventilation management and outcome of patients receiving intraoperative ventilation during general anesthesia– posthoc analysis of an observational study in 29 countries
Authors: Hol Liselotte , Nijbroek Sunny G. L. H. , Neto Ary Serpa , Hemmes Sabrine N. T. , Hedenstierna Goran , Hiesmayr Michael , Hollmann Markus W. , Mills Gary H. , Vidal Melo Marcos F. , Putensen Christian , Schmid Werner , Severgnini Paolo , Wrigge Hermann , de Abreu Marcelo Gama , Pelosi Paolo , Schultz Marcus J. ,   for the LAS VEGAS study–investigators
Published: January 2022

Background

The aim of this analysis is to determine geo–economic variations in epidemiology, ventilator settings and outcome in patients receiving general anesthesia for surgery.

Methods

Posthoc analysis of a worldwide study in 29 countries. Lower and upper middle–income countries (LMIC and UMIC), and high–income countries (HIC) were compared. The coprimary endpoint was the risk for and incidence of postoperative pulmonary complications (PPC); secondary endpoints were intraoperative ventilator settings, intraoperative complications, hospital stay and mortality.

Results

Of 9864 patients, 4% originated from LMIC, 11% from UMIC and 85% from HIC. The ARISCAT score was 17.5 [15.0–26.0] in LMIC, 16.0 [3.0–27.0] in UMIC and 15.0 [3.0–26.0] in HIC (P = .003). The incidence of PPC was 9.0% in LMIC, 3.2% in UMIC and 2.5% in HIC (P < .001). Median tidal volume in ml kg− 1 predicted bodyweight (PBW) was 8.6 [7.7–9.7] in LMIC, 8.4 [7.6–9.5] in UMIC and 8.1 [7.2–9.1] in HIC (P < .001). Median positive end–expiratory pressure in cmH2O was 3.3 [2.0–5.0]) in LMIC, 4.0 [3.0–5.0] in UMIC and 5.0 [3.0–5.0] in HIC (P < .001). Median driving pressure in cmH2O was 14.0 [11.5–18.0] in LMIC, 13.5 [11.0–16.0] in UMIC and 12.0 [10.0–15.0] in HIC (P < .001). Median fraction of inspired oxygen in % was 75 [50–80] in LMIC, 50 [50–63] in UMIC and 53 [45–70] in HIC (P < .001). Intraoperative complications occurred in 25.9% in LMIC, in 18.7% in UMIC and in 37.1% in HIC (P < .001). Hospital mortality was 0.0% in LMIC, 1.3% in UMIC and 0.6% in HIC (P = .009).

Conclusion

The risk for and incidence of PPC is higher in LMIC than in UMIC and HIC. Ventilation management could be improved in LMIC and UMIC.

Trial registration

Clinicaltrials.gov, identifier: NCT01601223.
Identification of causal effects in case-control studies
Authors: L. Penning de Vries Bas B. , Groenwold Rolf H. H.
Published: January 2022

Background

Case-control designs are an important yet commonly misunderstood tool in the epidemiologist’s arsenal for causal inference. We reconsider classical concepts, assumptions and principles and explore when the results of case-control studies can be endowed a causal interpretation.

Results

We establish how, and under which conditions, various causal estimands relating to intention-to-treat or per-protocol effects can be identified based on the data that are collected under popular sampling schemes (case-base, survivor, and risk-set sampling, with or without matching). We present a concise summary of our identification results that link the estimands to the (distribution of the) available data and articulate under which conditions these links hold.

Conclusion

The modern epidemiologist’s arsenal for causal inference is well-suited to make transparent for case-control designs what assumptions are necessary or sufficient to endow the respective study results with a causal interpretation and, in turn, help resolve or prevent misunderstanding. Our approach may inform future research on different estimands, other variations of the case-control design or settings with additional complexities.
Leveraging pleiotropic association using sparse group variable selection in genomics data
Authors: Sutton Matthew , Sugier Pierre-Emmanuel , Truong Therese , Liquet Benoit
Published: January 2022

Background

Genome-wide association studies (GWAS) have identified genetic variants associated with multiple complex diseases. We can leverage this phenomenon, known as pleiotropy, to integrate multiple data sources in a joint analysis. Often integrating additional information such as gene pathway knowledge can improve statistical efficiency and biological interpretation. In this article, we propose statistical methods which incorporate both gene pathway and pleiotropy knowledge to increase statistical power and identify important risk variants affecting multiple traits.

Methods

We propose novel feature selection methods for the group variable selection in multi-task regression problem. We develop penalised likelihood methods exploiting different penalties to induce structured sparsity at a gene (or pathway) and SNP level across all studies. We implement an alternating direction method of multipliers (ADMM) algorithm for our penalised regression methods. The performance of our approaches are compared to a subset based meta analysis approach on simulated data sets. A bootstrap sampling strategy is provided to explore the stability of the penalised methods.

Results

Our methods are applied to identify potential pleiotropy in an application considering the joint analysis of thyroid and breast cancers. The methods were able to detect eleven potential pleiotropic SNPs and six pathways. A simulation study found that our method was able to detect more true signals than a popular competing method while retaining a similar false discovery rate.

Conclusion

We developed feature selection methods for jointly analysing multiple logistic regression tasks where prior grouping knowledge is available. Our method performed well on both simulation studies and when applied to a real data analysis of multiple cancers.
Remote-controlled cholangiography injection device: first clinical study in China
Authors: Chen Huan , Shan Li-yu , Ma Tao , Wang Yue , Feng Zhe , Dong Ding-Hui , Lv Yi , Zhu Hao-Yang
Published: January 2022

Background

X-ray cholangiography is of great value in the imaging of biliary tract diseases; however, occupational radiation exposure is unavoidable. Moreover, clinicians must manually inject the contrast dye, which may result in a relatively high incidence of adverse reactions due to unstable injection pressure. Thus, there is a need to develop a novel remote-controlled cholangiography injection device.

Methods

Patients with external biliary drainage requiring cholangiography were included. A remote-controlled injection device was developed with three major components: an injection pump, a pressure sensor, and a wireless remote-control panel. Image quality, adverse reactions, and radiation dose were evaluated.

Results

Different kinds of X-ray cholangiography were successfully and smoothly performed using this remote-controlled injection device in all patients. The incidence of adverse reactions in the device group was significantly lower than that in the manual group (4.17% vs. 13.9%,P = 0.001), and increasing the injection pressure increased the incidence of adverse reactions. In addition, the device helped operators avoid ionizing radiation completely.

Conclusions

With good control of injection pressure (within 10 kPa), the remote-controlled cholangiography injection device could replace the need for the doctor to inject contrast agent with good security and effectivity. It is expected to be submitted for clinical application.
A predictive model for postoperative progressive haemorrhagic injury in traumatic brain injuries
Authors: Chen Tiange , Chen Siming , Wu Yun , Chen Yilei , Wang Lei , Liu Jinfang
Published: January 2022

Background

Progressive haemorrhagic injury after surgery in patients with traumatic brain injury often results in poor patient outcomes. This study aimed to develop and validate a practical predictive tool that can reliably estimate the risk of postoperative progressive haemorrhagic injury (PHI) in patients with traumatic brain injury (TBI).

Methods

Data from 645 patients who underwent surgery for TBI between March 2018 and December 2020 were collected. The outcome was postoperative intracranial PHI, which was assessed on postoperative computed tomography. The least absolute shrinkage and selection operator (LASSO) regression model, univariate analysis, and Delphi method were applied to select the most relevant prognostic predictors. We combined conventional coagulation test (CCT) data, thromboelastography (TEG) variables, and several predictors to develop a predictive model using binary logistic regression and then presented the results as a nomogram. The predictive performance of the model was assessed with calibration and discrimination. Internal validation was assessed.

Results

The signature, which consisted of 11 selected features, was significantly associated with intracranial PHI (p < 0.05, for both primary and validation cohorts). Predictors in the prediction nomogram included age, S-pressure, D-pressure, pulse, temperature, reaction time, PLT, prothrombin time, activated partial thromboplastin time, FIB, and kinetics values. The model showed good discrimination, with an area under the curve of 0.8694 (95% CI, 0.8083–0.9304), and good calibration.

Conclusion

This model is based on a nomogram incorporating CCT and TEG variables, which can be conveniently derived at hospital admission. It allows determination of this individual risk for postoperative intracranial PHI and will facilitate a timely intervention to improve outcomes.
Subacute thyroiditis during early pregnancy: a case report and literature review
Authors: Bai Chao-Fang , Shen Guang-Hui , Yang Ying , Yang Ke , R Hayden Melvin , Zhou Yuan-Yuan , Geng Xing-Qian
Published: January 2022

Background

Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy.

Case presentation

A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41.

Conclusion

SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.
The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study
Authors: Caramello Valeria , Macciotta Alessandra , Bar Fabrizio , Mussa Alessandro , De Leo Anna Maria , De Salve Alessandro Vincenzo , Nota Fabio , Sacerdote Carlotta , Ricceri Fulvio , Boccuzzi Adriana
Published: January 2022

Background

Patients that arrive in the emergency department (ED) with COVID-19-like syndromes testing negative at the first RT-PCR represent a clinical challenge because of the lack of evidence about their management available in the literature.

Our first aim was to quantify the proportion of patients testing negative at the first RT-PCR performed in our Emergency Department (ED) that were confirmed as having COVID-19 at the end of hospitalization by clinical judgment or by any subsequent microbiological testing. Secondly, we wanted to identify which variables that were available in the first assessment (ED variables) would have been useful in predicting patients, who at the end of the hospital stay were confirmed as having COVID-19 (false-negative at the first RT-PCR).

Methods

We retrospectively collected data of 115 negative patients from2020, March 1st to 2020, May 15th. Three experts revised patients’ charts collecting information on the whole hospital stay and defining patients as COVID-19 or NOT-COVID-19. We compared ED variables in the two groups by univariate analysis and logistic regression.

Results

We classified 66 patients as COVID-19 and identified the other 49 as having a differential diagnosis (NOT-COVID), with a concordance between the three experts of 0.77 (95% confidence interval (95%CI) 0.66- 0.73). Only 15% of patients tested positive to a subsequent RT-PCR test, accounting for 25% of the clinically suspected. Having fever (odds ratio (OR) 3.32, (95%CI 0.97-12.31), p = 0.06), showing a typical pattern at the first lung ultrasound (OR 6.09, (95%CI 0.87-54.65), p = 0.08) or computed tomography scan (OR 4.18, (95%CI 1.11-17.86), p = 0.04) were associated with a higher probability of having COVID-19.

Conclusions

In patients admitted to ED with COVID-19 symptoms and negative RT-PCR a comprehensive clinical evaluation integrated with lung ultrasound and computed tomography could help to detect COVID-19 patients with a false negative RT-PCR result.