bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgG4-related lung disease with recurrent pulmonary lesions during steroid therapy and difficulty in differentiating from malignancy: a case report
Authors: Okubo Tomohito , Nakashima Nariyasu , Tokunaga Yoshimasa , Kita Nobuyuki , Nakamura Hiroyuki , Ishikawa Ryou , Okada Setsuo , Go Tetsuhiko , Yokomise Hiroyasu 
Published: April 2022

Abstract
Background
Immunoglobulin G4-related disease (IgG4-RD) is characterized by the formation of inflammatory lesions with fibrosis and infiltration of IgG4-positive plasma cells and lymphocytes in various organs of the body. Since the first report of IgG4-related autoimmune pancreatitis, IgG4-RD affecting various organs has been reported; however, only a few reports of IgG4-related lung disease (IgG4-RLD) exist. In this report, we describe a case of IgG4-RLD that was difficult to differentiate from malignancy, and the usefulness of the surgical approach in determining the appropriate diagnosis and treatment plan.

Case presentation
A 61-year-old man was referred to our hospital after a chest radiograph revealed an abnormal chest shadow. At the time of his first visit, he had a slight fever and dyspnea on exertion. Chest computed tomography (CT) revealed a middle lobe hilar mass with irregular margins and swelling of the right hilar and mediastinal lymph nodes. These findings were not present on CT 1.5 years ago. 18F-fluorodeoxyglucose-positron emission tomography revealed a mass lesion with a maximum diameter of 5.5 cm, maximum standardized uptake value (SUVmax) of 11.0, and areas with high SUV in the hilar and mediastinal lymph nodes. We suspected lung cancer or malignant lymphoma and performed a thoracoscopic lung biopsy to confirm the diagnosis. Histopathological examination revealed no malignant findings, and IgG4-RLD was diagnosed. One month after treatment with prednisolone (PSL), the tumor had shrunk, but a CT scan during the third month of PSL treatment revealed multiple nodular shadows in both lungs. Considering the possibility of malignant complications and multiple lung metastases, we performed thoracoscopic partial lung resection of the new left lung nodules to determine the treatment strategy. Histopathological examination revealed no malignant findings in any of the lesions, and the patient was diagnosed with IgG4-RLD refractory to PSL monotherapy.

Conclusions
IgG4-RLD refractory to PSL monotherapy showed changes from a solitary large mass (pseudotumor) to multiple nodules on chest CT. It was difficult to distinguish malignancy from IgG4-RLD based on imaging tests and blood samples alone, and the surgical approach was useful in determining the appropriate diagnosis and treatment plan.
From non-targeted to targeted GC–MS metabolomics strategy for identification of TCM preparations containing natural and artificial musk
Authors: Ding Meng , Fan Jun-Li , Huang Dong-Fang , Jiang Yue , Li Meng-Ning , Zheng Yu-Qing , Yang Xiao-Ping , Li Ping , Yang Hua 
Published: April 2022

Abstract
Background
Moschus is a rare and precious natural medicine. Due to the properties of resources scarcity and expensive price of natural musk, artificial musk has been developed as substitute materials in some prescriptions. Rapid and accurate identification of natural or artificial musk in complex traditional Chinese medicine (TCM) preparations is also a challenge.

Method
A strategy from non-targeted to targeted gas chromatography-mass spectrometry (GC–MS) metabolomics was developed for discrimination of natural and artificial musk. Firstly, GC–MS-based non-targeted analysis combined with chemometrics was used to find the potential chemical markers to distinguish natural musk and artificial musk. Subsequently, targeted metabolomics was used to analyze musk in preparations with multiple reaction monitoring (MRM) mode by use gas chromatography coupled with triple quadrupole mass spectrometry (GC-QQQ MS).

Results
Two chemical markers named prasterone and androsterone have been selected and could be detected in all Compound Pien Tze Huang preparations (CPZHs) containing artificial musk, while the CPZHs containing natural musk did not detect two markers with S/N (signal to noise ratio) less than 3.

Conclusion
Our work provides an applicable approach to select the practical chemical markers for the assessment of musk in preparations to realize the traceability of musk in TCM and improve the quality control of musk-containing preparations.
Expanding the phenotype of TTLL5-associated retinal dystrophy: a case series
Authors: Oh Jin Kyun , Vargas Del Valle José G. , Lima de Carvalho Jose Ronaldo , Sun Young Joo , Levi Sarah R. , Ryu Joseph , Yang Jing , Nagasaki Takayuki , Emanuelli Andres , Rasool Nailyn , Allikmets Rando , Sparrow Janet R. , Izquierdo Natalio J. , Duncan Jacque L. , Mahajan Vinit B. , Tsang Stephen H. 
Published: April 2022

Abstract
Background
Inherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone–rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5. Examination of these patients included funduscopic evaluation, spectral-domain optical coherence tomography, short-wavelength autofluorescence, and full-field electroretinography (ffERG). Genetic diagnoses were confirmed using whole exome capture. Protein modeling of the identified variants was performed to explore potential genotype–phenotype correlations.

Results
Genetic testing revealed five novel variants in TTLL5 in three unrelated patients with retinal dystrophy. Clinical imaging demonstrated features of sectoral cone–rod dystrophy and cone dystrophy, with phenotypic variability seen across all three patients. One patient also developed high-frequency hearing loss during a similar time period as the onset of retinal disease, potentially suggestive of a syndromic disorder. Retinal structure findings were corroborated with functional measures including ffERG findings that supported these diagnoses. Modeling of the five variants suggest that they cause different effects on protein function, providing a potential reason for genotype–phenotype correlation in these patients.

Conclusions
The authors report retinal phenotypic findings in three unrelated patients with novel mutations causing autosomal recessive TTLL5-mediated retinal dystrophy. These findings broaden the understanding of the phenotypes associated with TTLL5-mediated retinal disease and suggest that mutations in TTLL5 should be considered as a potential cause of sectoral retinal dystrophy in addition to cone–rod and cone dystrophies.
Trend of hoverboard related injuries at a pediatric emergency department
Authors: Ferro Valentina , Nacca Raffaella , Boccuzzi Elena , Federici Tatiana , Ossella Chiara , Merenda Alessandra , Toniolo Renato Maria , Musolino Anna Maria , Reale Antonino , Raucci Umberto 
Published: April 2022

AbstractIntroductionUnderstanding how the use of hoverboards (HBs) can affect a child’s safety is crucial. We describe the characteristics of HB related injuries and provide key messages about child prevention when using these leisure devices.MethodsThis was a retrospective study at an emergency department (ED) of a level-III-trauma center from 2016 to 2019. We tested the differences in children presenting for injury associated with HBs between 2016-2017 and 2018-2019 to better describe the temporal trend of the phenomenon.ResultsThe rate ofInjury associated with HBs / Total injury per 1,000increased from 0.84 in 2016 to 7.7 in 2017, and then there was a gradual decline. The likelihood of injury was more common in younger children, increasing by 17% with decreasing age in 2018-2019 compared with 2016-2017 (OR: 0.83; 95%CI: 0.71-0.97;p= 0.021). The occurrence of injury in the April-June period was over twice as common in 2018-2019 (OR: 2.05; 95%CI: 1.0-2.05;p= 0.05). Patients were over 4 times more likely to have injured the lower extremity during the 2018-2019 period rather than other body regions (OR: 4.58; 95%CI: 1.23-4.58;p= 0.02). The odds of the indoor injury were more than twice as high in 2018-2019 (OR: 2.04; 95%CI: 1.077-2.04;p= 0.03).ConclusionDespite a decrease in the frequency of HB related injuries after 2017, during the 2018-2019 period, the younger the children, the more they were exposed to injury risk, in addition to a greater occurrence of indoor injuries from HBs compared with 2016-2017. The enhancement of preventive measures is necessary to ensure child safety when using HBs.
Digital therapeutics and the need for regulation: how to develop products that are innovative, patient-centric and safe
Authors: Rassi-Cruz Marcela , Valente Fernando , Caniza Maria Vanina 
Published: April 2022

Abstract
Background
Digital therapeutics are defined as therapeutic interventions that are driven by high quality software programs to prevent, manage or treat a medical disorder. These products provide great potential to improve patient outcomes, particularly for chronic disease sufferers, including people with Diabetes.

Main text
As yet, regulatory pathways for these products are rather unclear across all jurisdictions, although somewhat more progress has been made in the US and UK. Since digital therapeutics use cutting-edge technology and a logic of continuous innovation, regulation used for medical devices may not be completely appropriate. However, these products could present risks to patients if not developed and used appropriately. In the article, we consider the importance of a regulation framework and the role of self-regulation by developers as a way of ensuring patient safety while promoting innovation. We particularly emphasize the inclusion of doctors and other medical professionals in the design of the products, not only as a way of ensuring safe and effective applications, but also to encourage their take-up by patients, who tend to have high levels of trust for their HCPs.

Conclusion
Developers of digital therapeutics have the duty to create products that are safe, ethical and effective, without waiting for government regulation. Further, by self-regulating, following principles such as those provided by the Digital Therapeutics Alliance, they can develop products that serve patients better, while continuing to innovate.
A synthetic ‘essentialome’ for axenic culturing of ‘Candidatus Liberibacter asiaticus’
Authors: Cai Lulu , Jain Mukesh , Munoz-Bodnar Alejandra , Huguet-Tapia Jose C. , Gabriel Dean W. 
Published: April 2022

Abstract
Objective
‘Candidatus Liberibacter asiaticus’ (CLas) is associated with the devastating citrus ‘greening’ disease. All attempts to achieve axenic growth and complete Koch’s postulates with CLas have failed to date, at best yielding complex cocultures with very low CLas titers detectable only by PCR. Reductive genome evolution has rendered all pathogenic ‘Ca. Liberibacter’ spp. deficient in multiple key biosynthetic, metabolic and structural pathways that are highly unlikely to be rescued in vitro by media supplementation alone. By contrast, Liberibacter crescens (Lcr) is axenically cultured and its genome is both syntenic and highly similar to CLas. Our objective is to achieve replicative axenic growth of CLas via addition of missing culturability-related Lcr genes.

Results
Bioinformatic analyses identified 405 unique ORFs in Lcr but missing (or truncated) in all 24 sequenced CLas strains. Site-directed mutagenesis confirmed and extended published EZ-Tn5 mutagenesis data, allowing elimination of 310 of these 405 genes as nonessential, leaving 95 experimentally validated Lcr genes as essential for CLas growth in axenic culture. Experimental conditions for conjugation of large GFP-expressing plasmids from Escherichia coli to Lcr were successfully established for the first time, providing a practical method for transfer of large groups of ‘essential’ Lcr genes to CLas.
Long-term prophylaxis with lanadelumab for HAE: authorization for temporary use in France
Authors: Fain Olivier , Du-Thanh Aurelie , Gobert Delphine , Launay David , Inhaber Neil , Boudjemia Karima , Aubineau Magali , Sobel Alain , Boccon-Gibod Isabelle , Weiss Laurence , Bouillet Laurence 
Published: April 2022

AbstractBackgroundHereditary angioedema (HAE) is associated with a heavy burden of illness.ObjectiveTo evaluate use of lanadelumab in a French Authorization for Temporary Use (ATU) program.MethodsATU requests were made between October 12, 2018, and March 13, 2019; patients were followed through September 23, 2019. At entry, patients received lanadelumab 300 mg every 2 weeks. HAE attack characteristics were evaluated at day (D) 0 and months (M) 3 and 6. Patients completed the Angioedema Quality of Life (AE-QoL) questionnaire at initiation and monthly and the Angioedema Activity Score questionnaire daily in 28 day cycles (AAS28).ResultsIn total, 77 patients received ≥ 1 lanadelumab dose; 69 had ≥ 1 quarterly follow-up visit (analyzed population). Mean (standard deviation [SD]) lanadelumab exposure was 240.4 (53.7) days. Lanadelumab dose was modified in 12 patients (mostly to every 4 weeks). For the analyzed population, compared with attacks/month (mean [SD]) within 6 months before ATU (2.68 [2.54]), fewer attacks occurred between initiation and first visit (0.16 [0.42]; P < 0.001) or last visit (0.16 [0.42]; P < 0.001); D15 and last visit (0.15 [0.41]); and D70 and last visit (0.17 [0.70]). AE-QoL total and domain scores were significantly higher at initiation versus M3 and M6; 55% and 65% of patients, respectively, achieved a minimal clinically important difference from D0 to M3 and D0 to M6. Proportion of patients with AAS28 of 0 was higher during M3 (90%) and M6 (83%) than initiation (59%). The most frequently reported adverse events included headache (7.3%) and injection site pain (6.3%).ConclusionsLanadelumab reduced attack rates, improved quality of life, and was generally well tolerated.
Recurrent hepatocellular carcinoma with osteoclast-like giant cells: a case report
Authors: Tsukimoto Mone , Sugimoto Kazushi , Shigefuku Ryuta , Sugimoto Ryosuke , Yuasa Hiroto , Uchida Katsunori , Yamamoto Norihiko 
Published: April 2022

Abstract
Background
Hepatocellular carcinoma with osteoclast-like giant cells is very rare and has an extremely poor prognosis. Here, we report a case of hepatocellular carcinoma with osteoclast-like giant cells that had a relatively better prognosis.

Case presentation
A 70-year-old Japanese man with hepatitis B virus-related liver cirrhosis was admitted to our hospital for the treatment of recurrent hepatocellular carcinoma. At the age of 60 years, he was first diagnosed as having hepatocellular carcinoma in the right lobe (9 cm in diameter), and liver resection of segment 7/8 was performed. Histological findings showed well-differentiated hepatocellular carcinoma. Since then, imaging studies have been performed every 3 or 4 months. One year later, hepatocellular carcinoma recurred in the lateral segment, and radiofrequency ablation was performed. Nine years after the first presentation, hepatocellular carcinoma recurrences were detected in the caudate lobe and segment 5 by imaging studies. Surgical resection of the caudate lobe was performed, and ultrasonography-guided radiofrequency ablation was subsequently performed for the segment 5 tumor. The resected tumor was simple nodular, well-differentiated HCC; it measured 21 × 21 mm and contained many osteoclast-like giant cells. As neither vascular nor bile duct invasion was found, we believe that radical resection was achieved. Since then, the hepatocellular carcinoma has not recurred for over a year and a half.

Conclusion
Hepatocellular carcinoma with osteoclast-like giant cells is very rare and the prognosis is extremely poor, but early detection can lead to a better clinical course.
A “cluster” of ten uterine anomalies observed in a single center over a short period of 4 weeks: a case series
Authors: Kabadi Yogindrakumar M. , Ayyanar Abirami 
Published: April 2022

Abstract
Background
Uterine anomalies occur because of Müllerian duct maldevelopment. Few of them are associated with adverse obstetric outcome (Reyes-Muñoz et al. in Diagnostics. 2019;9:4. https://doi.org/10.3390/diagnostics9040149). Genital outflow tract obstructive uterine anomalies invariably present in the adolescent age group.

Case details
We report a case series of uterine anomalies. Ten such cases presented like a “cluster” within a short span of just one month. Eight of these ten cases were diagnosed intraoperatively during cesarean section. One case was diagnosed during laparoscopic sterilization, and the other case was diagnosed before doing manual vacuum aspiration. There were four cases of bicornuate uterus, two cases each of unicornuate uterus and uterine didelphys, and one case each of septate uterus and arcuate uterus. All eight babies were healthy and without any obvious congenital anomalies. To the best of the authors’ knowledge, literature regarding these anomalies has been mentioned mostly as case reports (Bruand et al. in Cureus. 2020;12:3. https://doi.org/10.7759/cureus.7191) and a few case series (Ross et al. in BMJ Case Rep. 2018. https://doi.org/10.1136/bcr-2017-221815). All women were of Kannadiga ethnicity and in the age range of 19–35 years. They were from places nearby to our institute within a range of approximately 250 km.

Conclusion
We describe herein almost all types of uterine anomalies. These rare uterine anomalies presented in a short span of just four weeks like a “cluster”. This incidental finding is unusual. We need to design studies to understand the reasons for clustering of such cases in our clinical practice.
Cell-free fat extract attenuates osteoarthritis via chondrocytes regeneration and macrophages immunomodulation
Authors: Jia Zhuoxuan , Kang Bijun , Cai Yizuo , Chen Chingyu , Yu Zheyuan , Li Wei , Zhang Wenjie 
Published: April 2022

AbstractBackgroundThe prevalence of osteoarthritis (OA) is increasing, yet clinically effective and economical treatments are unavailable. We have previously proposed a cell-free fat extract (CEFFE) containing multiple cytokines, which possessed antiapoptotic, anti-oxidative, and proliferation promotion functions, as a “cell-free” strategy. In this study, we aimed to evaluate the therapeutic effect of CEFFE in vivo and in vitro.MethodsIn vivo study, sodium iodoacetate-induced OA rats were treated with CEFFE by intra-articular injections for 8 weeks. Behavioral experiments were performed every two weeks. Histological analyses, anti-type II collagen, and toluidine staining provided structural evaluation. Macrophage infiltration was assessed by anti-CD68 and anti-CD206 staining. In vitro study, the effect of CEFFE on macrophage polarization and secretory factors was evaluated by flow cytometry, immunofluorescence, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of CEFFE on cartilage regeneration was accessed by cell counting kit-8 assay and qRT-PCR. The generation of reactive oxygen species (ROS) and levels of ROS-related enzymes were investigated by qRT-PCR and western blotting.ResultsIn rat models with sodium iodoacetate (MIA)-induced OA, CEFFE increased claw retraction pressure while decreasing bipedal pressure in a dose-dependent manner. Moreover, CEFFE promoted cartilage structure restoration and increased the proportion of CD206+macrophages in the synovium. In vitro, CEFFE decreased the proportion of CD86+cells and reduced the expression of pro-inflammatory factors in LPS + IFN-γ induced Raw 264.7. In addition, CEFFE decreased the expression of interleukin-6 and ADAMTs-5 and promoted the expression of SOX-9 in mouse primary chondrocytes. Besides, CEFFE reduced the intracellular levels of reactive oxygen species in both in vitro models through regulating ROS-related enzymes.ConclusionsCEFFE inhibits the progression of OA by promoting cartilage regeneration and limiting low-grade joint inflammation.Graphical abstract
Explaining and avoiding failure modes in goal-directed generation of small molecules
Authors: Langevin Maxime , Vuilleumier Rodolphe , Bianciotto Marc 
Published: April 2022

AbstractDespite growing interest and success in automated in-silico molecular design, questions remain regarding the ability of goal-directed generation algorithms to perform unbiased exploration of novel chemical spaces. A specific phenomenon has recently been highlighted: goal-directed generation guided with machine learning models produce molecules with high scores according to the optimization model, but low scores according to control models, even when trained on the same data distribution and the same target. In this work, we show that this worrisome behavior is actually due to issues with the predictive models and not the goal-directed generation algorithms. We show that with appropriate predictive models, this issue can be resolved, and molecules generated have high scores according to both the optimization and the control models.
On fractional order multiple integral transforms technique to handle three dimensional heat equation
Authors: Khan Tahir , Ahmad Saeed , Zaman Gul , Alzabut Jehad , Ullah Rahman 
Published: April 2022

AbstractIn this article, we extend the notion of double Laplace transformation to triple and fourth order. We first develop theory for the extended Laplace transformations and then exploit it for analytical solution of fractional order partial differential equations (FOPDEs) in three dimensions. The fractional derivatives have been taken in the Caputo sense. As a particular example, we consider a fractional order three dimensional homogeneous heat equation and apply the extended notion for its analytical solution. We then perform numerical simulations to support and verify our analytical calculations. We use Fox-function theory to present the derived solution in compact form.
A priori error analysis of virtual element method for contact problem
Authors: Wang Fei , Reddy B. Daya 
Published: April 2022

AbstractAs an extension of the finite element method, the virtual element method (VEM) can handle very general polygonal meshes, making it very suitable for non-matching meshes. In (Wriggers et al. in Comput. Mech. 58:1039–1050, 2016), the lowest-order virtual element method was applied to solve the contact problem of two elastic bodies on non-matching meshes. The numerical experiments showed the robustness and accuracy of the virtual element scheme. In this paper, we establish a priori error estimate of the virtual element method for the contact problem and prove that the lowest-order VEM achieves linear convergence order, which is optimal.