bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Open-label Phase I/IIa Clinical Trial of 11β-HSD1 Inhibitor for Cushing’s Syndrome and Autonomous Cortisol Secretion
Authors: Oda Satoko , Ashida Kenji , Uchiyama Makiko , Sakamoto Shohei , Hasuzawa Nao , Nagayama Ayako , Wang Lixiang , Nagata Hiromi , Sakamoto Ryuichi , Kishimoto Junji , Todaka Koji , Ogawa Yoshihiro , Nakanishi Yoichi , Nomura Masatoshi 
Published: June 2021

Abstract

Context
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors demonstrate antimetabolic and antisarcopenic effects in Cushing’s syndrome (CS) and autonomous cortisol secretion (ACS) patients.

Objective
To confirm the efficacy and safety of S-707106 (11β-HSD1 inhibitor) administered to CS and ACS patients.

Design
A 24-week single-center, open-label, single-arm, dose-escalation, investigator-initiated clinical trial on a database.

Setting
Kyushu University Hospital, Kurume University Hospital, and related facilities.

Patients
Sixteen patients with inoperable or recurrent CS and ACS, with mildly impaired glucose tolerance.

Intervention
Oral administration of 200 mg S-707106 after dinner, daily, for 24 weeks. In patients with insufficient improvement in oral glucose tolerance test results at 12 weeks, an escalated dose of S-707106 (200 mg twice daily) was administered for the residual 12 weeks.

Main Outcome Measures
The rate of participants responding to glucose tolerance impairment, defined as those showing a 25% reduction in the area under the curve (AUC) of plasma glucose during the 75-g oral glucose tolerance test at 24 weeks.

Results
S-707106 administration could not achieve the primary endpoint of this clinical trial (&gt;20% of responsive participants). AUC glucose decreased by −7.1% [SD, 14.8 (90% CI −14.8 to −1.0), P = 0.033] and −2.7% [14.5 (−10.2 to 3.4), P = 0.18] at 12 and 24 weeks, respectively. S-707106 administration decreased AUC glucose significantly in participants with a high body mass index. Body fat percentage decreased by −2.5% [1.7 (−3.3 to −1.8), P &lt; 0.001] and body muscle percentage increased by 2.4% [1.6 (1.7 to 3.1), P &lt; 0.001].

Conclusions
S-707106 is an effective insulin sensitizer and antisarcopenic and antiobesity medication for these patients.
IGF-I, Growth, and Body Composition in Preterm Infants up to Term Equivalent Age
Authors: Yumani Dana F J , Lafeber Harrie N , van Weissenbruch Mirjam M 
Published: June 2021

Abstract

Context
There are concerns that a higher fat mass in the early life of preterm infants is associated with adverse cardiometabolic outcomes in young adulthood.

Objective
To investigate the role of IGF-I and growth in determining body composition of preterm infants at term equivalent age.

Methods
An observational study was conducted from August 2015 to August 2018. From birth to term equivalent age, IGF-I levels were measured bi-weekly and growth was assessed weekly. At term equivalent age, body composition was assessed through air displacement plethysmography; 65 infants with a gestational age of 24 to 32 weeks were assessed at term equivalent age, of whom 58 completed body composition measurement. The main outcome measures were fat (free) mass (g) and fat (free) mass percentage at term equivalent age.

Results
In the first month of life, each 0.1 nmol/L per week increase in IGF-I was associated with a 465 g (SE 125 g) increase in fat free mass. A greater increase in weight SDS in the first month of life was associated with a higher fat free mass percentage (B 200.9; 95% CI, 12.1-389.6). A higher head circumference SDS was associated with more fat free mass (r = 0.46; 95% CI, 0.21-0.65). However, a greater increase in weight SDS up to term equivalent age was associated with a lower fat free mass percentage (B −55.7, SE 9.4).

Conclusion
These findings suggest that impaired growth in the first month of life is associated with a less favorable body composition at term equivalent age.
Asymmetric Synthesis of (−)-Atorvastatin Calcium by Tandem Catalysis
Authors: Murata Keisuke , Minami Riko , Fuwa Haruhiko 
Published: June 2021

Abstract
A seven-step synthesis of (−)-atorvastatin calcium, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has been developed. The key transformations of the present synthesis are a tandem olefin cross-metathesis/hemiacetalization/intramolecular oxa-Michael addition and a subsequent regioselective Baeyer–Villiger oxidation for the stereocontrolled construction of the syn-3,5-dihydroxy carboxylic acid substructure.
Ultra-high Capacity Li[Ni1/3Co1/3Mn1/3]O2 Cathode Synthesized Using a Novel MnO2 Template
Authors: Jang Hyun-Ju , Lee Seong-Hee , Park Eui-Jeong , Kim Hae-In , Son Jong-Tae 
Published: June 2021

Abstract
An ultra-high capacity Li[Ni1/3Co1/3Mn1/3]O2 (T-LNCM) cathode material was synthesized using a novel MnO2 template comprising nanorods of 114 nm diameter, which increased the surface area of the material to 3.19 m2 g−1. Owing to its large surface area and high lithium diffusion coefficient (4.72 × 10−14 cm2 s−1), T-LNCM exhibits an ultra-high capacity of 220.2 mAh g−1 at 0.1 C. The capacity of T-LNCM is significantly higher than that of the conventional LNCM cathode material.
Superior objective and subjective image quality of deep learning reconstruction for low-dose abdominal CT imaging in comparison with model-based iterative reconstruction and filtered back projection
Authors: Tamura Akio , Mukaida Eisuke , Ota Yoshitaka , Kamata Masayoshi , Abe Shun , Yoshioka Kunihiro 
Published: June 2021

Objective:
This study aimed to conduct objective and subjective comparisons of image quality among abdominal computed tomography (CT) reconstructions with deep learning reconstruction (DLR) algorithms, model-based iterative reconstruction (MBIR), and filtered back projection (FBP).

Methods:
Datasets from consecutive patients who underwent low-dose liver CT were retrospectively identified. Images were reconstructed using DLR, MBIR, and FBP. Mean image noise and contrast-to-noise ratio (CNR) were calculated, and noise, artifacts, sharpness, and overall image quality were subjectively assessed. Dunnett’s test was used for statistical comparisons.

Results:
Ninety patients (67 ± 12.7 years; 63 males; mean body mass index [BMI], 25.5 kg/m2) were included. The mean noise in the abdominal aorta and hepatic parenchyma of DLR was lower than that in FBP and MBIR (p &lt; .001). For FBP and MBIR, image noise was significantly higher for obese patients than for those with normal BMI. The CNR for the abdominal aorta and hepatic parenchyma was higher for DLR than for FBP and MBIR (p &lt; .001). MBIR images were subjectively rated as superior to FBP images in terms of noise, artifacts, sharpness, and overall quality (p &lt; .001). DLR images were rated as superior to MBIR images in terms of noise (p &lt; .001) and overall quality (p = .03).

Conclusions:
Based on objective and subjective comparisons, the image quality of DLR was found to be superior to that of MBIR and FBP on low-dose abdominal CT. DLR was the only method for which image noise was not higher for obese patients than for those with a normal BMI.

Advances in knowledge:
This study provides previously unavailable information on the properties of DLR systems and their clinical utility.
Μοντέλο ανάλυσης εικόνων για μαθητές Δημοτικού Σχολείου: ένα εργαλείο για την προώθηση κριτικού οπτικού γραμματισμού
Authors: Καραγιαννάκη Ευανθία 
Published: June 2021

Το παρόν άρθρο παρουσιάζει μια συστηματική διδακτική πορεία μύησης μικρών μαθητών Δημοτικού Σχολείου στην ανάγνωση εικόνων. Η εν λόγω προσέγγιση, η οποία συνιστά έρευνα δράσης, έλαβε χώρα στο πλαίσιο πολιτιστικών προγραμμάτων, που υλοποιήθηκαν κατά τις ώρες Ευέλικτης Ζώνης, στην Α΄ και Β΄ τάξη Δημοτικού Σχολείου Δυτικής Θεσσαλονίκης. Επισημαίνεται ότι η ομάδα των μαθητών που συμμετείχε στην εν λόγω έρευνα είναι σταθερή, καθώς η δράση-παρέμβαση εξελίχθηκε από το ένα σχολικό έτος στο άλλο. Το κειμενικό υλικό που αξιοποιήθηκε αντλήθηκε, αφενός, από την εικονογράφηση των δημοφιλέστερων παραμυθιών των μαθητών της Α΄ τάξης Δημοτικού και, αφετέρου, από αγαπημένους πίνακες ζωγραφικής των μαθητών της Β΄ τάξης Δημοτικού. Η δημοτικότητα του κειμενικού υλικού αναδείχθηκε μέσα από σύντομες συνεντεύξεις με τα παιδιά. Η προσέγγιση των εικόνων βασίστηκε στο μοντέλο των Kress & van Leeuwen, το οποίο η εκπαιδευτικός-ερευνήτρια μετασχημάτισε σε μοντέλο ανάλυσης εικόνων για παιδιά, ώστε να είναι προσιτό στους μικρούς μαθητές της. Επίσης, κατά την ανάλυση των εικόνων, η ερευνήτρια έλαβε υπόψη της στοιχεία κοινωνικής σημειωτικής, ώστε η ανάγνωσή τους να λάβει κριτικό χαρακτήρα. Τέλος, για μια πιο αποτελεσματική μελέτη των εικόνων, η ερευνήτρια δημιούργησε έναν κατάλογο σχημάτων οπτικού λόγου. Η προσέγγιση ήταν δραστηριοκεντρική, εκκινώντας πάντα από μια εικόνα, η οποία αποτελούσε τη βάση για προφορικές διεπιδράσεις κριτικής εμβάθυνσης, ενώ στη συνέχεια η διδασκαλία εμπλουτιζόταν με θεατρικά παιχνίδια και εικαστικές δημιουργίες. Η αξιολόγηση των παρεμβάσεων απέδειξε ότι η προσέγγιση που υιοθετήθηκε στάθηκε αποτελεσματική για τους μικρούς μαθητές, καθώς πλέον ήταν σε θέση να αποκωδικοποιούν τις εικόνες και να εμβαθύνουν σε αυτές. Βασικό συμπέρασμα της εν λόγω έρευνας ήταν ότι η εικόνα που αντιστοιχεί είτε σε εικονογράφηση παραμυθιού είτε σε πίνακα ζωγραφικής συνιστά πολύτιμο και πολύπλευρο διδακτικό και εποπτικό εργαλείο, καθώς, μέσα από την κατάλληλη αξιοποίησή της, συντελεί πρωτίστως στην προώθηση του οπτικού γραμματισμού και της κριτικής οπτικής επίγνωσης, καθώς επίσης στην όξυνση της κριτικής σκέψης και στην παραγωγή πλούσιου προφορικού λόγου σε διάφορες μορφές (περιγραφή, αφήγηση, επιχειρηματολογία, επεξήγηση). Παράλληλα δε, αποτελεί μοναδική πηγή έμπνευσης για θεατρικά δρώμενα και εικαστικές δημιουργίες, σε ένα πλαίσιο δόμησης και αναδόμησης του αρχικού οπτικού κειμένου.
Suspected botulism outbreak after the consumption of vegetarian pâté in the south of Viet Nam
Authors: Hung Le Quoc , Tho Vo Ngoc Anh , Khanh Do Thi Ngoc , Hien Vo Thi Thanh , Day Jeremy N. , Sang Nguyen Ngoc , Tam Hua Thoai , Thanh Ho Thi Chi , Ngan Nguyen Thi Thuy 
Published: June 2021

Botulism and other botulinum neurotoxins-producing clostridia are potentially life-threatening diseases caused by toxins produced by Clostridium botulinum. Here we reported a case series of six patients who presented with botulism following ingestion of commercially made pâté. The key features of presentation were acute onset of bilateral cranial nerve palsies and symmetrical descending weakness in the absence of fever resulting in the need for mechanical ventilation in all six patients. The clinical diagnosis of botulism was confirmed through the identification of C. botulinum from the suspected food source. Given that botulinum antitoxin was not available in Vietnam at the time, and their severe status, all patients received a trial of plasma exchange therapy, but no clear benefit was seen. Due to its rarity, diagnosing botulism is a challenge, demanding high clinical suspicion. Successful outcomes depend upon early recognition and rapid initiation of specific treatment with botulinum antitoxin. There is a need to improve global access to antitoxin. These cases, the first in Viet Nam, serve as a reminder of the need to maintain the highest possible food hygiene and preservation practices.
Impact of COVID-19 on non-COVID intensive care unit service utilization, case mix and outcomes: A registry-based analysis from India
Authors:   Indian Registry of IntenSive care (IRIS), KJ Adhikari Neill , Beane Abi , Devaprasad Dedeepiya , Fowler Robert , Haniffa Rashan , James Augustian , Jayakumar Devachandran , Kodippily Chamira , Aravindakshan Kooloth Rohit , Laxmappa Rakesh , Mangal Kishore , Mani Ashwin , Mathew Meghena , Pari Vrindha , Patodia Sristi , Pattnaik Rajyabardhan , Priyadarshini Dilanthi , Pulicken Mathew , Rabindrarajan Ebenezer , Ramachandran Pratheema , Ramesh Kavita , Rani Usha , Ramaiyan Ananth , Ramakrishnan Nagarajan , Ranganathan Lakshmi , Rashan Aasiyah , Dominic Savio Raymond , Selva Jaganathan , Tirupakuzhi Vijayaraghavan Bharath Kumar , Tripathy Swagata , Udayanga Ishara , Venkataraman Ramesh 
Published: June 2021

Background: Coronavirus disease 2019 (COVID-19) has been responsible for over 3.4 million deaths globally and over 25 million cases in India. As part of the response, India imposed a nation-wide lockdown and prioritized COVID-19 care in hospitals and intensive care units (ICUs). Leveraging data from the Indian Registry of IntenSive care, we sought to understand the impact of the COVID-19 pandemic on critical care service utilization, case-mix, and clinical outcomes in non-COVID ICUs. Methods: We included all consecutive patients admitted between 1st October 2019 and 27th September 2020. Data were extracted from the registry database and included patients admitted to the non-COVID or general ICUs at each of the sites. Outcomes included measures of resource-availability, utilisation, case-mix, acuity, and demand for ICU beds. We used a Mann-Whitney test to compare the pre-pandemic period (October 2019 - February 2020) to the pandemic period (March-September 2020). In addition, we also compared the period of intense lockdown (March-May 31st 2020) with the pre-pandemic period. Results: There were 3424 patient encounters in the pre-pandemic period and 3524 encounters in the pandemic period. Comparing these periods, weekly admissions declined (median [Q1 Q3] 160 [145,168] to 113 [98.5,134]; p=0.00002); unit turnover declined (median [Q1 Q3] 12.1 [11.32,13] to 8.58 [7.24,10], p<0.00001), and APACHE II score increased (median [Q1 Q3] 19 [19,20] to 21 [20,22] ; p<0.00001). Unadjusted ICU mortality increased (9.3% to 11.7%, p=0.01519) and the length of ICU stay was similar (median [Q1 Q3] 2.11 [2, 2] vs. 2.24 [2, 3] days; p=0.15096). Conclusion: Our registry-based analysis of the impact of COVID-19 on non-COVID critical care demonstrates significant disruptions to healthcare utilization during the pandemic and an increase in the severity of illness.
The association of preoperative blood markers with postoperative readmissions following arthroplasty
Authors: Khoshbin Amir , Hoit Graeme , Nowak Lauren Leone , Daud Anser , Steiner Martine , Juni Peter , Ravi Bheeshma , Atrey Amit 
Published: June 2021

Aims While preoperative bloodwork is routinely ordered, its value in determining which patients are at risk of postoperative readmission following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is unclear. The objective of this study was to determine which routinely ordered preoperative blood markers have the strongest association with acute hospital readmission for patients undergoing elective TKA and THA. Methods Two population-based retrospective cohorts were assembled for all adult primary elective TKA (n = 137,969) and THA (n = 78,532) patients between 2011 to 2018 across 678 North American hospitals using the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) registry. Six routinely ordered preoperative blood markers - albumin, haematocrit, platelet count, white blood cell count (WBC), estimated glomerular filtration rate (eGFR), and sodium level - were queried. The association between preoperative blood marker values and all-cause readmission within 30 days of surgery was compared using univariable analysis and multivariable logistic regression adjusted for relevant patient and treatment factors. Results The mean TKA age was 66.6 years (SD 9.6) with 62% being females (n = 85,163/137,969), while in the THA cohort the mean age was 64.7 years (SD 11.4) with 54% being female (n = 42,637/78,532). In both cohorts, preoperative hypoalbuminemia (< 35 g/l) was associated with a 1.5- and 1.8-times increased odds of 30-day readmission following TKA and THA, respectively. In TKA patients, decreased eGFR demonstrated the strongest association with acute readmission with a standardized odds ratio of 0.75 per two standard deviations increase (p < 0.0001). Conclusion In this population level cohort analysis of arthroplasty patients, low albumin demonstrated the strongest association with acute readmission in comparison to five other commonly ordered preoperative blood markers. Identification and optimization of preoperative hypoalbuminemia could help healthcare providers recognize and address at-risk patients undergoing TKA and THA. This is the most comprehensive and rigorous examination of the association between preoperative blood markers and readmission for TKA and THA patients to date. Cite this article: Bone Jt Open 2021;2(6):388–396.
A zero inflated log-normal model for inference of sparse microbial association networks
Authors: Prost Vincent , Gazut Stéphane , Brüls Thomas 
Published: June 2021

The advent of high-throughput metagenomic sequencing has prompted the development of efficient taxonomic profiling methods allowing to measure the presence, abundance and phylogeny of organisms in a wide range of environmental samples. Multivariate sequence-derived abundance data further has the potential to enable inference of ecological associations between microbial populations, but several technical issues need to be accounted for, like the compositional nature of the data, its extreme sparsity and overdispersion, as well as the frequent need to operate in under-determined regimes.The ecological network reconstruction problem is frequently cast into the paradigm of Gaussian Graphical Models (GGMs) for which efficient structure inference algorithms are available, like the graphical lasso and neighborhood selection. Unfortunately, GGMs or variants thereof can not properly account for the extremely sparse patterns occurring in real-world metagenomic taxonomic profiles. In particular, structural zeros (as opposed to sampling zeros) corresponding to true absences of biological signals fail to be properly handled by most statistical methods.We present here a zero-inflated log-normal graphical model (available athttps://github.com/vincentprost/Zi-LN) specifically aimed at handling such “biological” zeros, and demonstrate significant performance gains over state-of-the-art statistical methods for the inference of microbial association networks, with most notable gains obtained when analyzing taxonomic profiles displaying sparsity levels on par with real-world metagenomic datasets.
PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial
Authors: Celum Connie , Hosek Sybil , Tsholwana Mandisa , Kassim Sheetal , Mukaka Shorai , Dye Bonnie J. , Pathak Subash , Mgodi Nyaradzo , Bekker Linda-Gail , Donnell Deborah J. , Wilson Ethan , Yuha Krista , Anderson Peter L. , Agyei Yaw , Noble Heather , Rose Scott M. , Baeten Jared M. , Fogel Jessica M. , Adeyeye Adeola , Wiesner Lubbe , Rooney James , Delany-Moretlwe Sinead 
Published: June 2021

BackgroundPre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study.Methods and findingsHIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34;p= 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted.ConclusionsIn this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population.Trial registrationClinicalTrials.govNCT02732730.
Diagnosis of central serous chorioretinopathy by deep learning analysis of en face images of choroidal vasculature: A pilot study
Authors: Aoyama Yukihiro , Maruko Ichiro , Kawano Taizo , Yokoyama Tatsuro , Ogawa Yuki , Maruko Ruka , Iida Tomohiro 
Published: June 2021

Purpose
To diagnose central serous chorioretinopathy (CSC) by deep learning (DL) analyses of en face images of the choroidal vasculature obtained by optical coherence tomography (OCT) and to analyze the regions of interest for the DL from heatmaps.

Methods
One-hundred eyes were studied; 53 eyes with CSC and 47 normal eyes. Volume scans of 12×12 mm square were obtained at the same time as the OCT angiographic (OCTA) scans (Plex Elite 9000 Swept-Source OCT®, Zeiss). High-quality en face images of the choroidal vasculature of the segmentation slab of one-half of the subfoveal choroidal thickness were created for the analyses. The 100 en face images were divided into 80 for training and 20 for validation. Thus, we divided it into five groups of 20 eyes each, trained the remaining 80 eyes in each group, and then calculated the correct answer rate for each group by validation with 20 eyes. The Neural Network Console (NNC) developed by Sony and the Keras-Tensorflow backend developed by Google were used as the software for the classification with 16 layers of convolutional neural networks. The active region of the heatmap based on the feature quantity extracted by DL was also evaluated as the percentages with gradient-weighted class activation mapping implemented in Keras.

Results
The mean accuracy rate of the validation was 95% for NNC and 88% for Keras. This difference was not significant (P >0.1). The mean active region in the heatmap image was 12.5% in CSC eyes which was significantly lower than the 79.8% in normal eyes (P<0.01).

Conclusions
CSC can be automatically diagnosed by DL with high accuracy from en face images of the choroidal vasculature with different programs, convolutional layer structures, and small data sets. Heatmap analyses showed that the DL focused on the area occupied by the choroidal vessels and their uniformity. We conclude that DL can help in the diagnosis of CSC.