bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor DNA methylation marker MYO1-G for diagnosis and monitoring of colorectal cancer
Authors: Lin Wu-Hao , Xiao Jian , Ye Zi-Yi , Wei Da-Liang , Zhai Xiao-Hui , Xu Rui-Hua , Zeng Zhao-Lei , Luo Hui-Yan 
Published: December 2021

Abstract
Background
Circulating tumor DNA (ctDNA) is a promising diagnostic and prognostic marker for many cancers and has been actively investigated in recent years. Previous studies have already demonstrated the potential use of ctDNA methylation markers in the diagnosis and prognostication of colorectal cancer (CRC). This retrospective study validated the value of methylation biomarker MYO1-G (cg10673833) in CRC diagnosis and disease monitoring using digital droplet PCR (ddPCR), a biomarker selected from our previous study due to its highest diagnostic efficiency.

Methods
Blood samples of CRC and control samples from tumor-free individuals at two institutions were collected to quantify the methylation ratio using ddPCR. Area under curve (AUC) was calculated after constructing receiver operating characteristic curve (ROC) for CRC diagnosis. Sensitivity and specificity were estimated and comparisons of methylation ratio in different groups were performed.

Results
We collected 673 blood samples from 272 patients diagnosed with stage I-IV CRC and 402 normal control samples. The methylation biomarker discriminated patients with CRC from normal controls with high accuracy (area under curve [AUC] = 0.94) and yielded a sensitivity of 84.3% and specificity of 94.5%. Besides, methylation ratio of MYO1-G was associated with tumor burden and treatment response. The methylation ratio was significantly lower in patients after their radical operation than when compared with those before surgeries (P < 0.001). Methylation ratio was significantly higher in patients with disease progression than those with stable disease (P = 0.002) and those with complete response or partial response (P = 0.009).

Conclusions
Together, our study indicated that this methylation marker can serve as a potential biomarker for diagnosing and monitoring CRC.
Self-adaptive architectures in IoT systems: a systematic literature review
Authors: Alfonso Iván , Garcés Kelly , Castro Harold , Cabot Jordi 
Published: December 2021

AbstractOver the past few years, the relevance of the Internet of Things (IoT) has grown significantly and is now a key component of many industrial processes and even a transparent participant in various activities performed in our daily life. IoT systems are subjected to changes in the dynamic environments they operate in. These changes (e.g. variations in bandwidth consumption or new devices joining/leaving) may impact the Quality of Service (QoS) of the IoT system. A number of self-adaptation strategies for IoT architectures to better deal with these changes have been proposed in the literature. Nevertheless, they focus on isolated types of changes. We lack a comprehensive view of the trade-offs of each proposal and how they could be combined to cope with simultaneous events of different types.In this paper, we identify, analyze, and interpret relevant studies related to IoT adaptation and develop a comprehensive and holistic view of the interplay of different dynamic events, their consequences on QoS, and the alternatives for the adaptation. To do so, we have conducted a systematic literature review of existing scientific proposals and defined a research agenda for the near future based on the findings and weaknesses identified in the literature.
An 8-year-old-girl with juvenile dermatomyositis and autoimmune thyroiditis in Tanzania: a case report
Authors: Mussa Fatima , Nalitolela Neema , Fredrick Francis 
Published: December 2021

Abstract
Background
Juvenile dermatomyositis is an inflammatory disease of muscles, skin, and blood vessels of unknown cause affecting all age and ethnic groups, with a reported incidence of 1.9–4.1 per million. It manifests with weakness in axial and proximal muscles and typical skin lesions. Historically, the Bohan and Peter classification schema has been used to diagnose juvenile dermatomyositis.

Case presentation
We report an 8-year-old African female child, who presented with features of juvenile dermatomyositis and a rare association with subclinical autoimmune thyroiditis. This case illustrates the typical presentation, diagnosis, and treatment outcomes of this highly misdiagnosed condition.

Conclusion
Due to the limited resources and knowledge about this under-reported disease in resource-constrained settings, the characteristic manifestations of juvenile dermatomyositis can be easily missed and thus requires a high index of suspicion for earlier diagnosis and management.
Gestational breast cancer in a patient with Crohn’s disease: two case reports
Authors: Al-Arsan Al-Yaseen Mohammed , Haydar Salah Aldin , Alali Mousa , Saifo Maher 
Published: December 2021

Abstract
Background
Diagnosis of breast cancer during gestation is a rare occurrence. In addition, the diagnosis of breast cancer in a patient with Crohn’s disease is not common. We present a rare case of gestational breast cancer in a patient with Crohn’s disease, with a concurrent breast cancer diagnosis in her sister.

Case presentation
A 31-year-old Syrian woman with Crohn’s disease was diagnosed with breast cancer at 30 weeks gestation; she received neoadjuvant chemotherapy during gestation. Incidentally, her 37-year-old sister was also diagnosed concomitantly with breast cancer. Both sisters underwent and successfully completed surgery and adjuvant therapy. At a 5-year review, both patients showed no signs of recurrence. The Crohn’s disease symptoms have also improved after chemotherapy, and the baby born after gestational chemotherapy is currently 5 years old with normal psychomotor development and without any congenital malformations.

Conclusions
This case report highlights the impact of gestation on breast cancer outcomes, the possibility of giving chemotherapy during gestation, and the effect of chemotherapy on the symptoms of Crohn’s disease.
Thermococcus sp. KS-1 PPIase as a fusion partner improving soluble production of aromatic amino acid decarboxylase
Authors: Koyanagi Takashi , Hara Ayumi , Kobayashi Kanako , Habara Yuji , Nakagawa Akira , Minami Hiromichi , Katayama Takane , Misawa Norihiko 
Published: December 2021

AbstractPeptidyl-prolyl cis-trans isomerase (PPIase, EC 5.2.1.8) catalyzes the racemization reaction of proline residues on a polypeptide chain. This enzyme is also known to function as a molecular chaperon to stabilize protein conformation during the folding process. In this study, we noted FK506 binding protein (FKBP)-type PPIase from a hyperthemophilic archaeon Thermococcus sp. strain KS-1 (PPIase KS−1) to improve the solubility of Pseudomonas putida aromatic amino acid decarboxylase (AADC) that is an indispensable enzyme for fermentative production of plant isoquinoline alkaloids. AADC fused N-terminally with the PPIase KS−1 (PPIase KS−1-AADC), which was synthesized utilizing Escherichia coli host, showed improved solubility and, consequently, the cell-free extract from the recombinant strain exhibited 2.6- to 3.4-fold elevated AADC activity than that from the control strain that expressed the AADC gene without PPIase KS−1. On the other hand, its thermostability was slightly decreased by fusing PPIase KS−1. The recombinant E. coli cells expressing the PPIase KS−1-AADC gene produced dopamine and phenylethylamine from L-dopa and phenylalanine by two- and threefold faster, respectively, as compared with the control strain. We further demonstrated that the efficacy of PPIase KS−1-AADC in solubility and activity enhancement was a little but obviously higher than that of AADC fused N-terminally with NusA protein, which has been assumed to be the most effective protein solubilizer. These results suggest that PPIase KS−1 can be used as one of the best choices for producing heterologous proteins as active forms in E. coli.
A Customized Screening Tool Approach for the Development of a Self-Nanoemulsifying Drug Delivery System (SNEDDS)
Authors: Schmied Fabian-Pascal , Bernhardt Alexander , Engel Andrea , Klein Sandra 
Published: December 2021

AbstractThe present study focused on establishing a novel, (pre-)screening approach that enables the development of promising performing self-nanoemulsifying drug delivery systems (SNEDDSs) with a limited number of experiments. The strategic approach was based on first identifying appropriate excipients (oils/lipids, surfactants, and co-solvents) providing a high saturation solubility for lipophilic model compounds with poor aqueous solubility. Excipients meeting these requirements were selected for SNEDDS development, and a special triangular mixture design was applied for determining excipient ratios for the SNEDDS formulations. Celecoxib and fenofibrate were used as model drugs. Formulations were studied applying a specific combination of in vitro characterization methods. Specifications for a promising SNEDDS formulation were self-imposed: a very small droplet size (< 50 nm), a narrow size distribution of these droplets (PDI < 0.15) and a high transmittance following SNEDDS dispersion in water (> 99% in comparison with purified water). Excipients that provided a nanoemulsion after dispersion were combined, and ratios were optimized using a customized mapping method in a triangular mixture design. The best performing formulations were finally studied for their in vitro release performance. Results of the study demonstrate the efficiency of the customized screening tool approach. Since it enables successful SNEDDS development in a short time with manageable resources, this novel screening tool approach could play an important role in future SNEDDS development.
Subanesthetic Dose of Propofol Activates the Reward System in Rats
Authors: Nagata Isao , Sasaki Mika , Miyazaki Tomoyuki , Saeki Kensuke , Ogawa Ken-ichi , Kamiya Yoshinori 
Published: December 2021

BACKGROUND:
Propofol has addictive properties, even with a single administration, and facilitates dopamine secretion in the nucleus accumbens (NAc). Activation of the dopaminergic circuits of the midbrain reward system, including the ventral tegmental area (VTA) and NAc, plays a crucial role in addiction. However, the effects of propofol on synaptic transmission and biochemical changes in the VTA-NAc circuit remain unclear.

METHODS:
We investigated the effects of subanesthetic doses of propofol on rat VTA neurons and excitatory synaptic transmission in the NAc using slice patch-clamp experiments. Using immunohistochemistry and western blot analyses, we evaluated the effects of intraperitoneal propofol administration on the expression of addiction-associated transcription factor ΔFosB (truncated form of the FBJ murine osteosarcoma viral oncogene homolog B protein) in the NAcs in 5-week-old rats.

RESULTS:
In the current-clamp mode, a subanesthetic dose (0.5–5 µmol/L) of propofol increased the action potential frequency in about half the VTA neurons (excited neurons: control: 9.4 ± 3.0 Hz, propofol 0.5 µmol/L: 21.5 ± 6.0 Hz, propofol 5 µmol/L: 14.6 ± 5.3 Hz, wash: 2.0 ± 0.7 Hz, n = 14/27 cells; unchanged/suppressed neurons: control: 1.68 ± 0.94 Hz, propofol 0.5 µmol/L: 1.0 ± 0.67 Hz, propofol 5 µmol/L: 0.89 ± 0.87 Hz, wash: 0.16 ± 0.11 Hz, n = 13/27 cells). In the voltage-clamp mode, about half the VTA principal neurons showed inward currents with 5 µmol/L of propofol (inward current neurons: control: −20.5 ± 10.0 pA, propofol 0.5 µmol/L: −62.6 ± 14.4 pA, propofol 5 µmol/L: −85.2 ± 18.3 pA, propofol 50 µmol/L: −17.1 ± 39.2 pA, washout: +30.5 ± 33.9 pA, n = 6/11 cells; outward current neurons: control: −33.9 ± 14.6 pA, propofol 0.5 µmol/L: −29.5 ± 16.0 pA, propofol 5 µmol/L: −0.5 ± 20.9 pA, propofol 50 µmol/L: +38.9 ± 18.5 pA, washout: +40.8 ± 32.1 pA, n = 5/11 cells). Moreover, 0.5 µmol/L propofol increased the amplitudes of evoked excitatory synaptic currents in the NAc, whereas >5 µmol/L propofol decreased them (control: 100.0 ± 2.0%, propofol 0.5 µmol/L: 118.4 ± 4.3%, propofol 5 µmol/L: 98.3 ± 3.3%, wash [within 10 min]: 70.7 ± 3.3%, wash [30 minutes later]: 89.9 ± 2.5%, n = 13 cells, P < .001, Dunnett’s test comparing control and propofol 0.5 µmol/L). Intraperitoneally administered subanesthetic dose of propofol increased ΔFosB expression in the NAc, but not in VTA, 2 and 24 hours after administration, compared with the Intralipid control group (propofol 2 hours: 0.94 ± 0.15, 24 hours: 0.68 ± 0.07; Intralipid 2 hours: 0.40 ± 0.03, 24 hours: 0.37 ± 0.06, P = .0002 for drug in the 2-way analysis of variance).

CONCLUSIONS:
Even a single administration of a subanesthetic dose of propofol may cause rewarding change in the central nervous system. Thus, there is a potential propofol rewarding effect among patients receiving anesthesia or sedation with propofol, as well as among health care providers exposed to propofol.
The Strategy to Implement Work-Based Learning through Field Work Practices in Vocational High Schools (Multiple Case Studies in Malang Regency and Blitar City)
Authors: Hanindya Defris , Yoto Yoto , Nyoto Amat 
Published: December 2021

This study aims to identify and describe the strategy for implementing work-based learning through fieldwork practices in vocational high schools which include (1) WBL-FWP implementation strategy planning; (2) WBL-FWP implementation strategy; (3) Evaluation of the WBL-FWP implementation strategy; (4) Supporting and inhibiting factors for WBL-FWP Implementation, and (5) Impact on WBL-FWP implementation. This study uses a qualitative approach and the type of research is Multi Cases, the research was conducted at VHS Turen and VHS Islam 1 Blitar. Sources of data were obtained from the principal, vice-principal for public relations, the Chair of the WBL-FWP Working Group, the WBL-FWP Supervisor, and the WBL-FWP Instructor.Â Collecting data using free and in-depth interviews, study documentation, and observation. The findings show that: (1) WBL-FWP implementation strategy planning is carried out by MoU with linear industry, WBL-FWP supporting industrial practice equipment, and student preparation with WBL-FWP program socialization and debriefing; (2) The WBL-FWP implementation strategy is carried out structurally, the WBL-FWP is implemented for 6 months and there is a pick-up after students complete the WBL-FWP; (3) Evaluation of the WBL-FWP implementation strategy includes the assessment of industrial work results and the assessment of supervisors; (4) The supporting and implementing factors of WBL-FWP are the enthusiasm and full support of all school residents and the limitations of the industry as the location of WBL-FWP, the presence of students to improve products, teachers gain experience and apply learning in schools, and students gain competence in industry; (5) The impact of the existence of WBL-FWP is that the name of VHS will be better known, and students will also gain knowledge outside and know more about how to communicate, socialize with those around them.
Olha Já! Construção gramatical no Amazonas
Authors: Siqueira Gislane Aparecida Martins 
Published: December 2021

Neste trabalho, propõe-se o estudo da microconstrução amazonense olha já, apoiado teoricamente em pressupostos da Gramática de Construções, com foco especial na menção de Croft (2007) de que as estruturas sintática e semântica compõem a anatomia de uma construção podendo ser os conceitos fundamentais e os termos descritivos para a análise da estrutura de uma construção gramatical. Por meio das análises sintática e semântica se constatam a organização da composição e a compreensão global da microconstrução. Propõe-se ainda uma sugestão de sua atuação na língua. No decorrer do trabalho, constata-se no português brasileiro a existência de outras microconstruções compostas pela mesma regra da composição de olha já, o que permitiu atestar a produtividade do padrão.
La primera versión argentina de los Grundlinien der Philosophie des Rechts de Hegel: la mediación político-textual en la traducción de Angélica Mendoza
Authors: Turri Fernando Juan 
Published: December 2021

Durante las primeras décadas del siglo XX no abundan traducciones españolas de los Grundlinien der Philosophie des Rechts. En 1937, se publica en la Editorial Claridad la traducción de Angélica Mendoza, la cual no sólo representa la primera versión argentina de los Grundlinien, sino que también es la primera y única completa que se ofrece al mundo hispano-parlante hasta 1975 cuando aparezca la traducción de J. L. Vermal. Pero esta primera edición completa de la obra no puede omitir el contexto político-cultural al que pertenecieron tanto la traductora como la editorial, ni tampoco los recursos de los que se valió Mendoza para realizar esta tarea.
En el siguiente trabajo nos proponemos examinar críticamente la versión realizada por Angélica Mendoza de los Grundlinien, sosteniendo que hay dos mediaciones determinadas que intervienen en el acceso de la obra hegeliana: una de carácter político y la otra de carácter textual. En primer lugar, considerando la fecha de publicación de la traducción, pretendemos mostrar los elementos que implican el rol mediador del marxismo para el acceso de los Grundlinien. En segundo lugar, mediante una valoración crítica de la traducción, destacaremos el rol mediador que cumple la versión italiana de Messineo tanto para beneficio de la traducción en español, como para los problemas de comprensión que se derivan de este recurso indirecto.
Conjuntivismo, disyuntivismo y fenomenología husserliana
Authors: Rubio Roberto , Pereira Francisco 
Published: December 2021

El presente trabajo intenta poner de relieve algunos de los principales desafíos que trae consigo la tarea de situar a Husserl en el debate entre conjuntivistas y disyuntivistas. Para ello, realizaremos un análisis crítico de la discusión desarrollada por Overgaard (2018). Sobre la base de dicho análisis, expondremos tres desafíos: en primer lugar, el desafío de sistematizar apropiadamente las discrepancias fundamentales y los elementos en común entre las posiciones conjuntivista y disyuntivista; en segundo lugar, el desafío de utilizar con claridad y precisión las nociones básicas en las que tradicionalmente se ha articulado el debate. Por último, abordaremos desafíos específicos relativos a la interpretación de la fenomenología de Husserl.
Penguatan Pendidikan Karakter melalui Program Konseling Pondok Pesantren Mahir Arriyadl di Keling Kepung Kediri
Authors: Anwar Khoirul 
Published: December 2021

Penelitian ini bertujuan untuk menganalisa tentang penguatan pendidikan karakter melalui Program Konseling Pondok Pesantren Mahir Arriyadl di Keling Kepung Kediri. Penelitian ini menggunakan pendekatan kualitatif. Peneliti mendapatkan data menggunakan metode wawancara, observasi, dan dokumentasi. Tahap-tahap penelitian meliputi pengumpulan data, reduksi data, penyajian data, dan penarikan kesimpulan. Temuan penelitian ini berupa: (1) Penerapan Penguatan Pendidikan karakter melalui program konseling di Pondok Pesantren Mahir Arriyadl Keling Kepung Kediri dilatarbelakangi oleh rasa tanggung jawab pondok dalam melaksanakan secara langsung kepada para santri tentang materi-materi yang sudah diajarkan terutama adap tingkah laku melalui program konseling, serta penerapan tata tertib pondok pesantren menjadikan para santri menjadi terbiasa dengan peraturan yang ada di pondok (2) Aktualisasi penguatan pendidikan karakter dilakukan dengan pendekatan berbasis individu, keluarga, pondok, dan masyarakat dalam satu kesatuanyang utuh dan saling terkait (3) Upaya strategis pondok pesantren dalam meningkatkan program penguatan pendidikan karakter melalui program konseling yaitu menjadikan pendidikan karakter bagian dari kurikulum, pemenuhan sarana dan prasarana yang memadai, menyatukan visi sumber daya manusia.[This study aims to analyze the strengthening of character education through the Mahir Arriyadl Islamic Boarding School Counseling Program in Keling Kepung Kediri. This study uses a qualitative approach. Researchers get data using interviews, observation, and documentation. The research stages include data collection, data reduction, data presentation, and drawing conclusions. The findings of this study are: (1) The application of strengthening character education through a counseling program at the Pondok Pesantren Mahir Arriyadl Keling Kepung Kediri is motivated by the sense of responsibility of the cottage in implementing directly to the students about the materials that have been taught, especially behavior through the counseling program. , as well as the application of boarding school rules and regulations to make students familiar with the existing regulations in the boarding school (2) Actualization of strengthening character education is carried out with an individual, family, cottage, and community-based approach in a unified and interrelated unit (3) Strategic efforts Islamic boarding schools in improving character education strengthening programs through counseling programs, namely making character education part of the curriculum, fulfilling adequate facilities and infrastructure, unifying the vision of human resources.]
Aktivitas Enzimatis Biakan Kapang Aspergillus Section Nigri DUCC (Diponegoro University Culture Collection) Dan Identifikasi Molekuler Isolat Potensial
Authors: Sabrini Zalia , Rukmi Isworo , Ferniah Rejeki Siti 
Published: December 2021

The enzyme amylase, cellulase and protease are an extracellular enzymes are many produced by microorganisms such as fungi Aspergillus section Nigri. This research aims to find out the potential biakanes of Aspergillus section Nigri DUCC collection (Diponegoro University Culture Collection) which is capable to produce some enzymes that consists of amylase, protease and celullase and also identification in molecular based. Activity enzymatic assay of Aspergillus section Nigri with semi-quantitative method using selective medium, CMC for cellulolytic, Starch agar 1% for amylolytic and Skim Milk agar for proteolytic. Biakane potential is determined by looking at the Enzymatic Index (EI) is highest for all of three enzyme. Molecular identification is using the universal primer ITS4 and ITS5. The results showed that the culture of DUCC K207 has high activity for all of three enzyme. Index enzymatic of isolate DUCC K207 , 1.55 mm for amylolytic, 1.49 mm for cellulolytic and 1, 24 mm for proteolytic. Result of molecular identification DUCC K207 known as Aspergillus niger that has 100% similarity with Aspergillus niger MH 109325.1.
Optimal Enforcement for Content Industries under Positive External Effects of Piracy
Authors: Domon Koji 
Published: December 2021

Abstract
Content industries have several profit sources that positively interact with one another, and piracy affects them not only negatively but also positively. For copyright holders, choosing to allow piracy depends upon its total external effects. This paper proves that in such case the profit function is convex with respect to the level of enforcement. This paper shows a convex profit function with respect to the level of enforcement. The convexity leads to a corner solution of optimal enforcement for copyright holders. Which corner solution is selected depends on the relative size of the sub-market, and no enforcement is profitable if the submarket size is relatively large. This result compensates for a shortcoming of discussions that assume only two options regarding the level of enforcement, zero or perfect enforcement.