Identification of an at-risk subpopulation with high immune infiltration based on the peroxisome pathway and TIM3 in colorectal cancer

Background Peroxisomes are pivotal metabolic organelles that exist in almost all eukaryote cells. A reduction in numbers and enzymatic activities of peroxisomes was found in colon adenocarcinomas. However, the role of peroxisomes or the peroxisome pathway in colorectal cancer (CRC) is not defined. Methods In the current study, a peroxisome score was calculated to indicate the activity of the peroxisome pathway using gene set variant analysis based on transcriptomic datasets. CIBERSORTx was chosen to infer enriched immune cells for tumors among subgroups. The SubMap algorithm was applied to predict its sensitivity to immunotherapy. Results The patients with a relatively low peroxisome score and high level of T-cell immunoglobulin and mucin domain 3 (TIM-3) presented the worse overall survival than others. Moreover, low peroxisome scores were associated with high infiltration of lymphocytes and poor prognosis in those CRC patients. Thus, a PERLowTIM3High CRC risk subpopulation was identified and characterized by high immune infiltration. The results also showed that CD8 T cells and macrophages highly infiltrated tumors of the PERLowTIM3High group, regardless of consortium molecular subtype and microsatellite instability status. This subgroup had the highest tumor mutational burden and overexpression of immune checkpoint genes. Further, the PERLowTIM3High group showed a higher probability of responding to programmed cell death protein-1-based immunotherapy. In addition, genes involved in peroxisomal metabolic processes in CRC were also investigated since peroxisome is a rather pleiotropic and highly metabolic organelle in cell. The results indicated that only those genes involved in fatty acid alpha oxidation could be used to stratify CRC patients as similar as peroxisome pathway genes. Conclusions We revealed the favorable prognostic value of the peroxisome pathway in CRC and provided a new CRC stratification based on peroxisomes and TIM3, which might be helpful for CRC diagnostics and personalized treatment.

Genomic analyses identify biological processes in ZKSCAN3-deficient colorectal cancer cells

Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) is associated with cell differentiation, cell proliferation and apoptosis, which has been reported as a critical driver of colorectal cancer. However, the mechanism and function of ZKSCAN3 in colorectal cancer is still unclear. Here, our objective is to identify the functional molecules and signaling by analyzing the RNA-seq data. The GSE172201 was created by the Illumina NovaSeq 6000 (Homo sapiens). The KEGG and GO analyses indicated the immune defense response to virus and transcription activity are major processes in the ZKSCAN3 KO colorectal cancer cells. Moreover, we determined ten key molecules including STAT1, MX1, DDX58, PPARG, EGFR, APP, BST2, DLG4, OASL, and IFIT2. Therefore, our study may provide the novel knowledge of ZKSCAN3 mediated colorectal cancer.

Pengaruh Konseling Home care Terhadap Kualitas Hidup Penderita DM Tipe 2 Di Puskesmas Talise Kota Palu

Penderita Diabetes Melitus umumnya memiliki kualitas hidup yang buruk dibandingkan dengan orang yang tanpa penyakit sehingga membutuhkan perawatan diabetes yang tepat melalui intervensi perilaku berupa dukungan pendidikan dan konseling untuk mengaktifkan penderita diabetes untuk mengelola penyakitnya. Penelitian ini bertujuan untuk mengetahui pengaruh konseling dalam home care terhadap kualitas hidup penderita Diabetes Mellitus Tipe 2. Penelitian ini dilaksanakan di wilayah kerja Puskesmas Talise dan wilayah kerja Puskesmas Birobuli Kota Palu. Desain penelitian adalah Eksperimen Semu dengan jumlah sampel sebanyak 40 responden yang dipilih secara acak. Analisis data menggunakan Uji Beda Dua Mean yaitu Uji Wilcoxon dan Uji Beda Dua Mean Independen yaitu Uji Mann Whitney. Hasil penelitian menunjukkan ada pengaruh konseling home care terhadap kualitas hidup penderita DM baik pada Domain 1 (Kesehatan Fisik), Domain 2 (Kondisi Psikologis), Domain 3 (Hubungan Sosial), Domain 4 (Lingkungan) dimana skor rata- rata (mean) sebelum intervensi adalah 60,55 dengan standar deviasi 2,605 meningkat menjadi 71,35 dengan standar deviasi 4,107 setelah intervensi. Secara statistik terjadi perbedaan kualitas hidup sebelum dan setelah diberikan konseling dengan nilai p= 0,000 (p<0,05) yang berarti bahwa konseling home care efektif diberikan pada penderita DM untuk meningkatkan kualitas hidup penderita DM.

Palliative care volunteer roles in Nordic countries: qualitative studies—systematic review and thematic synthesis

BackgroundGiven limited palliative care resources, volunteers can be viewed as essential. To better understand the contribution of volunteers, it is useful to look at their roles in care systems with high level of financed public welfare, such as those found in Nordic countries.AimTo develop research-based knowledge of experiences related to volunteer roles in palliative care in Nordic countries with similar welfare systems.DesignSystematic review and thematic synthesis of qualitative studies.Data sourcesCinahl, APA PsycInfo, SocINDEX, Idunn, Cristin, SwePub, SweMed+, Doria and Danish Research Database from 2005 to 2020.Eligibility criteriaQualitative peer-reviewed studies reporting first-hand experience of volunteers in palliative care in hospital, community (homecare and nursing home) and hospice settings (hospice institution and hospice home care); English abstract and available full text.ResultsOf 1521 citations, 11 articles were included in the review: seven Norwegian articles, three Swedish articles and one Danish article. Three overall themes emerged from analysis: (1) volunteers offered something different than professionals, (2) volunteering took place in professionals’ domain, (3) volunteers were motivated by personal gains.ConclusionVolunteers provide valuable support to patients and next of kin that differs from professionals’ support. Volunteers are motivated by direct interaction with patients and next of kin. Opportunities for interactions depend on the healthcare setting and professionals’ understandings of volunteers’ role. Formal training of volunteers is limited and supportive available professionals important to volunteers. Professionals’ understandings of volunteers’ role should be improved to strengthen volunteers’ role in palliative care in Nordic countries.PROSPERO registration numberCRD42020222695.

Fast Healthcare Interoperability Resources (FHIR) for Interoperability in Health Research: A Systematic Review (Preprint)

BACKGROUND The standard Fast Healthcare Interoperability Resources (FHIR) is widely used in health information technology. However, its use as a standard for health research is still less prevalent. To use existing data sources more efficiently for health research, data interoperability becomes increasingly important. FHIR provides solutions by offering resource domains such as “Public Health & Research” and “Evidence-Based Medicine” while using already established web technologies. Therefore, FHIR could help to standardize data across different data sources and improve interoperability in health research. OBJECTIVE The aim of our study was to provide a systematic review of existing literature and determine the current state of FHIR implementations in health research and possible future directions. METHODS We searched PubMed/Medline, EMBASE, Web of Science, IEEE Xplore and the Cochrane Library databases for studies published from 2010 to 2021. Studies investigating the use of FHIR in health research were included. Articles published before 2010, abstracts, reviews, editorials and expert opinions were excluded. We followed the PRISMA guidelines and registered this study with PROSPERO, CRD42021235393. Data synthesis was done in tables and figures. RESULTS We identified a total of 674 studies, of which 28 studies were eligible for inclusion. Most studies covered the domain of clinical research (22/28) while the remaining studies focused on public health/ epidemiology (3/28) or did not specify their research domain (3/28). Studies used FHIR for data capture (11/28), standardization of data (7/28), analysis (4/28), recruitment (4/28) and consent management (2/28). Most studies had a generic approach (15/28) and nine of 13 studies focusing on specific medical specialties (infectious disease, genomics, oncology, environmental health, imaging, pulmonary hypertension) reported their solutions to be conferrable to other use cases. Half of the studies reported using additional data models or terminologies: SNOMED CT (8/14), LOINC (8/14), ICD-10 (6/14), OMOP CDM (3/14) and others (9/14). Only one study used a FHIR resource from the domain “Public Health & Research”. Limitations using FHIR included the possible change in the content of FHIR resources, safety and legal matters and the need for a FHIR server. CONCLUSIONS Our review found that FHIR can be implemented in health research and that the areas of application are broad and generalizable in most use cases. Implementation of international terminologies was common and other standards such as OMOP CDM could be used complementary with FHIR. Limitations such as change of FHIR content, lack of FHIR implementation, safety and legal matters need to be addressed in future releases to expand the use of FHIR and therefore interoperability in health research.

ANALISIS TATA KELOLA TEKNOLOGI INFORMASI PADA TVRI PAPUA MENGGUNAKAN COBIT 5.0 DOMAIN MEA

TVRI Papua Kota Jayapura telah menerapkan TI dalam proses operasionalnya seperti sistem informasi FileZilla. Tata Kelola Teknologi Informasi pada TVRI Papua pada bidang pemberitaan menggunakan framework COBIT 5 berdasarkan data yang diperoleh yang menghasilkan tingkat kematangan pada domain 3 MEA yang berbeda-beda. MEA01 (Monitoring, Evaluasi dan Penilaian Kinerja dan Kesesuaian), berada pada tingkat kematangan level 2 Managed Process bahwa kinerja TI-nya sudah standard dan berjalan dengan baik. MEA02 (Monitoring, Evaluasi dan Penilaian Sistem Kontrol Internal), berada pada tingkat kematangan level 3 Established Process bahwa pengendalian sepenuhnya berjalan sesuai dengan strategis organisasi Tugas Pokok dan Fungsi (Tupoksi). MEA03 (Monitoring, Evaluasi dan Penilaian Kepatuhan dan Persyaratan Eksternal), berada pada tingkat kematangan level 2 (Managed Process) dimana proses TI maupun proses bisnis sesuai dengan hukum serta kebijakan yang diterapkan. Dalam hal ini TVRI Papua Kota Jayapura agar lebih efisien dalam penggunaan TI diperlukan beberapa penanganan sehingga penggunaan FileZilla sesuai dengan strategis organisasi Tugas Pokok dan Fungsi (Tupoksi).

STUDY OF SANSKRIT LEARNING AT DVĪPĀNTARA SAṀSKṚTAM FOUNDATION IN DENPASAR CITY

<p>Sanskrit is the language used in the holy Vedic texts. To understand the contents of the Veda, it is very important to learn Sanskrit to know every meaning of the verse or mantra contained in the Veda scriptures. However, the existence of Sanskrit at this time has not been touched at all by Hindus and is very familiar with the use of Sanskrit. Sanskrit is only studied in institutions or colleges with Hindu nuances, so Hindus today have very little to know, let alone learn it. Besides that, Sanskrit is quite complex, there are many rules in learning it, so that Sanskrit is said to be a complex language and difficult to learn. The results of this study indicate the following points. First, the Sanskrit learning pattern at the Dvīpāntara Saṁskṛtam Foundation, starting in terms of tiered Sanskrit learning strategies, student center strategies, online Sanskrit learning strategies (patrālayadvārā Saṁskṛtam), learning methods using dialogue methods, storytelling methods as well as playing methods, learning media using image media and power point media, and using direct learning models Second, the problems faced in learning Sanskrit at the Dvīpāntara Saṁskṛtam Foundation in Denpasar City are caused by two factors, namely problems from internal factors which include perceptions, attitudes and motivation as well as from external factors such as educators, learning climate and infrastructure Third, the implications of learning Sanskrit at the Dvīpāntara Saṁskṛtam Foundation in Denpasar City include four aspects, namely: (1) cognitive domain, (2) affective domain, ( 3) psychomotor domain (4) literature and culture.</p>

Intrinsic contractile dysfunction in a surgical model of muscle hypertrophy

Synergistic ablation (SA) is widely used to induce muscle hypertrophy in rodent studies. However, it has been demonstrated that SA-induced compensatory hypertrophy induces increases in maximum isometric force that are smaller in magnitude than the increase in muscle cross-sectional area, suggesting a reduction in the specific force production due to intrinsic contractile dysfunction in the hypertrophied fibers. Here, by using the mechanical skinned fibers, we investigated the mechanisms behind the reduction in specific force in the compensatory hypertrophied muscles. Rats had unilateral surgical ablation of the gastrocnemius and soleus muscles to induce the compensatory hypertrophy in the plantaris muscles. Two wk after surgery, the mean fiber diameter was increased by 19% in the SA group compared with the contralateral control (CNT) group. In contrast, compared with the CNT group, both the depolarization-induced force (−51%) and the Ca2+-activated maximum specific force (−32%) were markedly reduced in skinned fibers from the SA group. These deleterious functional alterations were accompanied by decreases in the amount of DHPRα1, RYR, junctophilin 1, and SH3 and cysteine-rich domain 3 (STAC3) in SA muscles. Thus, these data clearly show that SA induces not only an increase in skeletal muscle fiber hypertrophy but also leads to a reduction in the intrinsic contractile dysfunction due to the excitation–contraction uncoupling and impaired force-generating capacity.

Isometric training improves fatigue resistance in dystrophin-deficient muscle

Eccentric contractions, in which the muscle is stretched during contraction, cause substantially greater damage than isometric (ISO) contractions, in which the length of the muscle does not change during contraction. Here, we tested the hypothesis that ISO training improves fatigue resistance in skeletal muscle from dystrophin-deficient mdx52 mice (15–22 wk old). ISO training (100 Hz stimulation frequency, 0.25-s contractions every 0.5 s, 6 sets of 60 contractions) was performed on the left plantar flexor muscles in vivo with supramaximal electrical stimulation every other day for 4 wk. Compared with the normal control muscle, resistance to fatigue was reduced in the nontrained muscle from mdx52 mice, which was accompanied by a reduction in citrate synthase activity and the LC3BII/I ratio and an increase in the phosphorylation levels of Akt Ser473 and the expression levels of p62. ISO training restored these alterations and markedly increased in vivo fatigue resistance and PGC-1α expression in mdx52 muscles. Moreover, an increased number of Evans Blue dye-positive fibers was significantly reduced by ISO training in mdx52 muscles. In contrast, ISO training did not restore a reduction in the amount of SH3 and cysteine-rich domain 3 in mdx muscles. Thus, our data suggest that mitochondrial function is impaired in dystrophin-deficient muscles, which is likely to be induced by the defective autophagy due to persistent activation of Akt. ISO training inhibits the aberrant activation of Akt presumably by up-regulating the PGC-1α expression, which results in improved mitochondrial function and thus fatigue resistance in dystrophin-deficient muscles.

Preconditioning contractions prevent Ca2+-dependent proteolysis of STAC3 and prolonged force depression after eccentric contractions

Preconditioning contractions (PCs) have been shown to markedly improve recovery from force depression after damaging eccentric contractions (ECCs). Here, we examined the mechanism underlying the effects of PCs with special focus on the SH3 and cysteine rich domain 3 (STAC3) that is essential for the transduction of action potential to the Ca2+ release from the sarcoplasmic reticulum. Rat medial gastrocnemius (MG) muscles were removed immediately (REC0), 1 d (REC1), and 4 d (REC4) after exposure to 100 repeated in vivo damaging ECCs. PCs with 10 repeated nondamaging ECCs were applied 2 d before the damaging ECCs. Damaging ECCs induced in vivo isometric torque depression at 50 and 100 Hz stimulation frequencies at REC1 and REC4, which was accompanied by a significant reduction in the amount of STAC3, an activation of calpain 1, and an increased number of Evans Blue dye positive fibers in MG muscles. Importantly, PCs attenuated all these deleterious alterations induced by damaging ECCs. Moreover, mechanistic experiments performed on normal muscle tissue exposed to various concentration of Ca2+ showed a Ca2+-dependent proteolysis of STAC3, which was prevented by calpain inhibitor MDL-28170. In conclusion, PCs improve recovery from force depression after damaging ECCs, presumably by inhibiting the loss of STAC3 due to the increased permeability of cell membrane and subsequent activation of calpain 1.