bluuebunny/crossref_metadata_2025 huggingface dataset:
Micronutrient Status and their Deficiency Diagnosed through DRIS in Tomato Growing Areas
Authors: Manzoor Rabia , Akhtar Mohammad Saleem , Khan Khalid Saifullah , Rosen Carl
Published: July 2022

The nutritional imbalances in tomato plants determined on the basis of soil and plant tests with interpretations on the critical nutrient level are less well correlated with the corresponding crop yields. Nutrient imbalance in tomatoes yield was assessed using Diagnosis and Recommendation Integrated System (DRIS) approach was more efficient. The study objectives were to evaluate micronutrient status in tomato growing areas and determine the nutrient(s) limiting tomato yield and establish DRIS norms for micronutrients for tomato crop. Twenty-six tomato fields from Chatter plain (Khyber Pakhtunkhwa), and Sheikupura (Punjab) were collected with soil, accompanying leaf index tissue and tomato yield was recorded. Tomato yield data were recorded and divided into high- (≥3.90 kg per 10 plants) and low- yield (3.95 kg per 10 plants) populations. DRIS analysis identified a deficiency of iron in the tomato production areas. Norms established through DRIS can be used for potential tomato yield.
Oral Hygiene dalam Pencegahan Ventilator-Associated Pneumonia pada Pasien Kritis: Literature Review
Authors: Utami Yuli Wahyu , Kristinawati Beti
Published: July 2022

Ventilator-associated pneumonia (VAP) dapat terjadi pada pasien kritis yang dilakukan pemasangan ventilasi mekanis 48 jam setelah intubasi. Kejadian VAP ini dapat dicegah dengan melakukan bundle VAP yang salah satunya dengan melakukan oral hygiene menggunakan bahan antiseptik yang efektif membunuh kuman. Literature review ini bertujuan untuk menganalisis bahan yang efektif digunakan dalam melakukan oral hygiene. Sejumlah 25 artikel dari 1728 artikel terpilih dalam review. Tinjauan sistematis dilakukan menggunakan teknik pelaporan Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Penelusuran artikel dilakukan melalui database online Pubmed, Scientdirect, dan Google Scholar. Artikel dibatasi pada jenis dan tahun (10 tahun terakhir), namun tidak dengan bahasa. Hasil review menunjukkan bahan yang digunakan untuk oral hygiene dan terbukti efektif dalam pencegahan VAP adalah bahan yang mengandung antibakteri dan antiseptik. Kesimpulan literature review ini yaitu oral hygiene dengan menggunakan bahan yang mampu menekan pertumbuhan dan membunuh bakteri terbukti dapat mencegah terjadinya VAP.
Peran Pemerintah dalam Perlindungan Tenaga Kesehatan Terpapar Covid–19
Authors: Effendi Rustam , Handayani Handayani
Published: July 2022

Angka kejadian Covid-19 di Indonesia terkonfirmasi sangat tinggi. Angka sebaran per tanggal 27 Juni 2021 terkonfirmasi 2.093.962, meninggal 56.729 dan sembuh 1.842.457. Peran pemerintah dalam perlindungan tenaga kesehatan sangat dibutuhkan. Beberapa kebijakan dari pemerintah termaktub di dalam ketetapan peraturan diantaranya adanya pemberian bonus dan kompensasi kematian bagi tenaga kesehatan serta program vaksin Covid-19 bagi tenaga medis. Upaya pemerintah dalam mencegah penyebaran dan penularan virus Corona diantaranya kebijakan stay at home, memakai masker, dan mencuci tangan. Penelitian ini bertujuan untuk menganalisis tahapan-tahapan yang sudah kerjakan oleh pemerintah Indonesia ketika menangani Covid-19 serta dalam melindungi tenaga kesehatan. Penelitian ini menggunakan systemic literature review. Dari 7 artikel yang didapat, Indonesia sudah menerapkan kebijakan pengendalian dan pencegahan penularan Covid-19. Kebijakan dari pemerintah membutuhkan dukungan, peran serta dan kesadaran masyarakat. Peraturan dan sistem kesehatan yang baik dan terorganisir dibutuhkan. Koordinasi yang terpola antar stake holder, khususnya  pemerintah  pusat dan pemerintah daerah, serta SOP pencegahan dan pengendalian Covid-19 diperlukan untuk menghambat penyebaran infeksi Covid-19 secara tuntas.
The Hubungan Kebugaran dengan Prestasi Akademik Masa Pandemi Covid-19
Authors: Sajodin Sajodin
Published: July 2022

Kebugaran merupakan komponen penting bagi mahasiswa untuk melaksanakan kegiatan perkuliahan. Perkuliahan daring masa pandemi Covid-19 dalam jangka waktu lama mengakibatkan kejenuhan, kurang konstrasi saat pembelajaran, sehingga menyebabkan penurunan aktivitas fisik sehingga dapat mempengaruhi kebugaran yang dapat mempengaruhi prestasi akademik mereka. Tujuan penelitian ini untuk menganalisis hubungan kebugaran dengan prestasi. Penelitian ini menggunakan metode deskripsi korelasional dengan desain cross sectional. Populasi dalam penelitian ini sebanyak 155 mahasiswa, jumlah sampel digunakan rumus Slovin sehingga sampel sebanyah 61 mahasiswa. Hasil penelitian ini menunjukkan tingkat kebugaran berada pada kategori sangat baik, sedangkan prsetasi akademik kategori baik. Adapun hasil uji Spearman Rank didapatka p-value sebesar 0,341>0,05, dapat disimpulkan tidak adanya hubungan yang bermakna kebugaran dengan prestasi akademik.
Hubungan antara Komponen Health Belief Model dengan Perilaku Pencegahan Covid-19 pada Masyarakat
Authors: Purnama Putri , Yulistiani Mustiah
Published: July 2022

Ancaman global Covid-19 terus muncul dan korban terus bertambah sehingga penting meningkatkan pengetahuan dan persepsi masyarakat untuk membentuk perilaku tindakan pencegahan penularan Covid-19. Tujuan penelitian ini untuk mengetahui hubungan komponen health belief model dengan perilaku pencegahan Covid-19 pada masyarakat Kecamatan Langensari Kota Banjar Jawa Barat. Penelitian ini bersifat deskriptif analitis dengan desain cross-sectional. Responden penelitian ini adalah masyarakat kecamatan Langensari dengan jumlah sampel sebanyak 100 responden yang dipilih dengan teknik purposive sampling. Pengambilan data menggunakan kuesioner yang dibagikan melalui google form. Hasil uji chi-square memperoleh hasil perceived susceptibility sebesar 0,000, perceived severity sebesar 0,005, perceived benefit sebesar 0,000, perceived barriers sebesar 0,860, cues to action sebesar  0,000, self-efficacy sebesar 0,000 dan nilai signifikansi p<0,05. Ada hubungan antara perceived susceptibility, perceived severity, perceived benefit, cues to action, self-efficacy dengan perilaku pencegahan covid-19, tetapi tidak ada hubungan antara percived barriers dan perilaku pencegahan Covid-19 (p>0,005). Dari 6 komponen health belief model, self-efficacy memiliki nilai korelasi tertinggi dan berpengaruh dalam melakukan tindakan pencegahan Covid-19 sementara itu yang tidak berpengaruh adalah perceived barriers.
Studi Literatur: Pengalaman Perawat ICU dalam Memberikan Asuhan Keperawatan Spiritual pada Pasien End of Life Care di Masa Pandemi Covid-19
Authors: Nurjanah Evi , Mediani Henny Suzana , Emaliyawati Etika
Published: July 2022

Spiritual care termasuk kedalam komponen end of life care yang berperan memberikan rasa nyaman dan damai pada pasien dan meringankan proses berduka bagi keluarga. Akan tetapi, pandemi Covid-19 menyebabkan banyaknya tantangan pada perawat ICU dalam pelaksanaan spiritual care. Penelitian ini bertujuan untuk mengidentifikasi bukti-bukti empiris mengenai pengalaman perawat ICU dalam memberikan spiritual care pada pasien end of life di masa pandemi Covid-19. Metode penelitian menggunakan literature review yang menganalisis artikel dari 5 database, yaitu Pubmed, Proquest, CINAHL, Science Direct, dan Google Scholar dengan rentang tahun publikasi antara 2020-2022. Kata kunci yang digunakan ‘pandemic Covid-19’, ‘critical care nursing’, ‘end of life care’, ‘dying’, ‘spiritual care’, dan ‘nursing experience’. Artikel diseleksi secara bertahap menggunakan alur PRISMA. 2.727 artikel yang teridentifikasi diseleksi berdasarkan duplikasi dan kriteria inklusi sehingga didapatkan 6 artikel yang layak dianalisis. Hasil analisis menunjukkan bahwa selama pandemi COVID-19 spiritual care merupakan domain yang penting dalam perawatan pasien menjelang ajal. Spiritual care pada pasien end of life dapat mengurangi kecemasan dan meringankan proses berduka bagi keluarga. Pelaksanaan spiritual care di masa pandemi mengalami banyak tantangan sehingga dibutuhkan strategi inovatif dalam mengimplementasikannya. Fasilitas pelayanan kesehatan diharapkan dapat memberikan dukungan kepada perawat untuk melaksanakan spiritual care dengan meningkatkan kompetensi perawat melalui pendidikan dan pelatihan.
ELEMEN IDEMPOTEN DI GELANGGANG Z_n DAN KAITANNYA DENGAN HOMOMORFISMA GELANGGANG
Authors: Aditya Ricky , Herawati Maria Vianney Any
Published: July 2022

Homomorfisma gelanggang merupakan salah satu topik yang dipelajari dalam perkuliahan aljabar abstrak untuk jenjang S1. Definisi dari homomorfisma gelanggang merupakan perluasan dari definisi homomorfisma grup, dengan sifat “mengawetkan struktur” berlaku untuk kedua operasi binernya. Karena aksiomanya lebih banyak, akan lebih sulit untuk mencari contoh-contoh dari homomorfisma gelanggang daripada contoh-contoh homomorfisma grup. Dalam makalah ini akan dikaji suatu karakterisasi dari homomorfisma gelanggang untuk kasus spesifik dari Z_m ke Z_n, yang ternyata berkaitan erat dengan elemen idempoten di gelanggang Z_n. Karakterisasi lebih detail untuk berbagai macam kemungkinan keterkaitan antara nilai m dan n juga akan dipaparkan. Dengan menggunakan karakterisasi-karakterisasi tersebut, akan lebih mudah bagi para dosen pengampu mata kuliah aljabar abstrak dalam memberikan contoh-contoh homomorfisma gelanggang.
IMPLEMENTASI WEIGHT PRODUCT MODEL (WPM) DALAM MEMILIH JENIS ASURANSI
Authors: Andriani Siska , Akhmad Dinar Munggaran , Ulya Muhammad
Published: July 2022

Asuransi merupakan suatu alat untuk mengurangi risiko keuangan, dengan cara pengumpulan unit-unit exposure dalam jumlah yang memadai, untuk membuat agar kerugian individu dapat diperkirakan. Dalam menentukan pilihan pada suatu produk atau jenis asuransi, kerap sekali ditemukan kasus-kasus atau masalah-masalah yang dihadapi oleh calon nasabah, seperti salah memilih jenis asuransi yang akhirnya akan menimbulkan rasa ketidakpuasan terhadap suatu layanan asuransi yang dipilih. Hal ini disebabkan karena kurangnya pemahaman dari nasabah terhadap detail dan kegunaan dari produk-produk yang ditawarkan, dan bila hal itu terus berlanjut, maka akan ada banyak nasabah yang merasa bahwa pelayanan yang didapatkan tidak cocok bahkan tidak memuaskan yang pada akhirnya nasabah tersebut tidak ingin memakai lagi jasa asuransi tersebut dikemudian hari. penelitian ini adalah merancang dan mengimplementasikan Sistem Pendukung Keputusan Berbasis Web Untuk Pemilihan Jenis Asuransi Bagi Calon Nasabah Dengan Metode Weighted Product. Nasabah akan mendapatkan hasil keputusan untuk menentukan jenis asuransi menggunakan metode weight product.
The effects of lactic acid bacteria and molasses on microbial community and fermentation performance of mixed silage of king grass and cassava foliage
Authors: Liu Yue , Chen Ting , Sun Rong , Zi Xuejuan , Li Mao
Published: July 2022

In the present study, we aim to investigate the effects of lactic acid bacteria (LAB) and molasses (M) on the microbial community and fermentation performance of mixed silage of king grass (KG) and cassava foliage (CF). A completely randomized design was used for the experiment. Mixed material was ensiled with no additive added (CK) for 60 days. Alternatively, mixed silage was supplemented with M, LAB (L), or M + LAB (ML) and then subjected to fermentation. Compared with the CK group, the contents of lactic acid and propionic acid in the L group were enhanced, whereas the content of acetic acid was reduced. Moreover, the levels of pH, butyric acid, and ammonia-N were not significantly changed. In contrast, the lower contents of pH, acetic acid, propionic acid, and butyric acid, as well as ammonia-N in the M and ML groups were observed, whereas the content of lactic acid was elevated. Additives could change the silage quality of mixed silage to different extents. The effect of the L treatment was not ideal, and the ML group had a better fermentation quality compared with the M group. In terms of microbial community, the relative abundance of desirable Lactobacillus was increased in the M, L, and ML groups. The relative abundance of Pseudomonas was decreased in the M and L groups. Compared with the CK group, the relative abundance of Stenotrophomonas was decreased, especially in the M (0.18%) and ML (0.19%) groups. For Paenibacillus, its relative abundance was increased in the ML group and more significantly increased in the M group. In summary, the combination of LAB and M at an equal ratio had a more positive effect on the fermentation quality and microbial community of mixed silage than LAB and M alone.
ChanFAD: A Functional Annotation Database for Ion Channels
Authors: Castro Elizabeth V. , Shepherd John W. , Guggenheim Ryan S. , Sengvoravong Manimone , Hall Bailey C. , Chappell McKenzie K. , Hearn Jessica A. , Caraccio Olivia N. , Bissman Cora , Lantow Sydney , Buehner Damian , Costlow Harry R. , Prather David M. , Zonza Abigail M. , Witt Mallory , Zahratka Jeffrey A.
Published: July 2022

Ion channels are integral membrane protein complexes critical for regulation of membrane potential, cell volume, and other signaling events. As complex molecular assemblies with many interacting partners, ion channels have multiple structural and functional domains. While channel sequence and functional data are readily available across multiple online resources, there is an unmet need for functional annotation directly relating primary sequence information, 2D interactions, and three-dimensional protein structure. To this end, we present ChanFAD (Channel Functional Annotation Database), to provide the research community with a centralized resource for ion channel structure and functional data. ChanFAD provides functional annotation of PDB structures built on the National Center for Biotechnology Information’s iCn3D structure viewing tool while providing additional information such as primary sequence, organism, and relevant links to other databases. Here we provide a brief tour of ChanFAD functionality while showing example use cases involving drug-channel interactions and structural changes based on mutation. ChanFAD is freely available and can be accessed at https://www.chanfad.org/.
A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model
Authors: Marzagalli Monica , Pelizzoni Giorgia , Fedi Arianna , Vitale Chiara , Fontana Fabrizio , Bruno Silvia , Poggi Alessandro , Dondero Alessandra , Aiello Maurizio , Castriconi Roberta , Bottino Cristina , Scaglione Silvia
Published: July 2022

The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous “extravasation” process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect (tumor cell apoptosis). Since NK cells infiltration and phenotype is correlated with prognosis and response to immunotherapy, their phenotype is also investigated: most importantly, a clear decrease in CD16-positive NK cells within the migrated and infiltrated population is observed. The proposed immune-tumor OOC-based model represents a promising approach for faithfully recapitulating the human pathology and efficiently employing the immunotherapies testing, eventually in a personalized perspective. An immune-organ on chip to recapitulate the tumor-mediated infiltration of circulating immune cells within 3D tumor model.
Autocrine/Paracrine Slit–Robo Signaling Controls Optic Lobe Development in Drosophila melanogaster
Authors: González-Ramírez M. Constanza , Rojo-Cortés Francisca , Candia Noemí , Garay-Montecinos Jorge , Guzmán-Palma Pablo , Campusano Jorge M. , Oliva Carlos
Published: July 2022

Cell segregation mechanisms play essential roles during the development of the central nervous system (CNS) to support its organization into distinct compartments. The Slit protein is a secreted signal, classically considered a paracrine repellent for axonal growth through Robo receptors. However, its function in the compartmentalization of CNS is less explored. In this work, we show that Slit and Robo3 are expressed in the same neuronal population of the Drosophila optic lobe, where they are required for the correct compartmentalization of optic lobe neuropils by the action of an autocrine/paracrine mechanism. We characterize the endocytic route followed by the Slit/Robo3 complex and detected genetic interactions with genes involved in endocytosis and actin dynamics. Thus, we report that the Slit-Robo3 pathway regulates the morphogenesis of the optic lobe through an atypical autocrine/paracrine mechanism in addition to its role in axon guidance, and in association with proteins of the endocytic pathway and small GTPases.
Short-term and long-term alterations of gastrointestinal microbiota with different H. pylori eradication regimens: A meta-analysis
Authors: Chen Bing , Li Xin-meng , Cai Ting , Wang Fen
Published: July 2022

Background and Aims

The impacts of Helicobacter pylori (H. pylori) eradication on the gastrointestinal microbiota are controversial, and whether the short-term and long-term changes in the gastrointestinal microbiota following different eradication regimens are consistent remains inconclusive. This study aimed to examine the effects of various eradication regimens on the gastrointestinal microflora at follow-up evaluations within 7 days, at 1–3 months, and over 6 months changes in the gastrointestinal microbiota.

Materials and Methods

Studies reported on the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrails.gov databases before March 2022 were collected. Data analysis and visualization were conducted using Review Manager 5.4.1. The tool of the Cochrane Collaboration to assess the risk of bias was suitable for randomized controlled trials with the Newcastle–Ottawa scale for nonrandomized controlled trials. In addition, the process was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Results

After a series of rigorous screenings, a total of 34 articles with 1,204 participants were included for this review analysis. The results showed changes in the gut microflora at the phylum level or the family and genus levels. After metronidazole-containing triple therapy, the number of Enterobacteriaceae increased at 1–3 months follow-up. After Metronidazole-free triple therapy, Actinobacteria decreased significantly, and this trend lasted for more than 6 months. Within 7 days after eradication treatment, the follow-up results showed a decrease in the number of Lactobacillus. After Bismuth-containing quadruple therapy, the changes in Actinobacteria fluctuated with the follow-up time. The changes in Proteobacteria showed a downward trend lasting for 1–3 months after eradication but returned to baseline levels over 6 months after eradication. Subgroup analyses indicated that host age could influence changes in the gut microbiota.

Conclusion

Different eradication regimens had varied effects on the short-term and long-term abundance of the gastrointestinal microbiota, but the decreasing trend of the microbiota diversity was the same for all regimens at the short-term follow-up. This study summarizes the changes of gut microbiota at different stages after different eradication regimens and hope to provide some references for supplementing probiotics, while further studies is needed to support these findings.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021292726
The controlling nutritional status score and clinical outcomes in patients with heart failure: Pool analysis of observational studies
Authors: Huang Xian-Wen , Luo Jian-Jing , Baldinger Beatrice
Published: July 2022

Background and aims

Malnutrition is very common in patients with heart failure (HF) and is associated with a worse clinical outcome. The Controlling Nutritional Status (CONUT) score is an easily derived index for the evaluation of malnutrition. This study aimed to evaluate the association between the CONUT score and the prognosis in patients with HF.

Methods and results

Electronic databases were searched for potential studies from inception up to February 15, 2022. Observational cohort studies included adult participants with HF, and reported the associations between the CONUT score and the adjusted relative risk (RR) of all-cause mortality, and patients with composite major adverse cardiac outcomes (MACEs) were included. We finally included 18 studies comprising 12,532 participants with HF for analysis. The median age of the patients was 70.5 years old, and 35.4% were women. After a median follow-up duration of 32.5 months, patients with HF with a higher CONUT score were associated with a higher risk of all-cause mortality (per 1 increment of the CONUT score: RR, 1.21, 95% CI, 1.13–1.29, I2 = 68%, P for heterogeneity = 0.002) and MACEs (per 1 increment of the CONUT score: RR, 1.14, 95% CI, 1.06–1.23, I2 = 81%, P for heterogeneity <0.0001) after adjusting for other prognostic factors. When the CONUT score was divided into the normal nutritional status and malnourished status, malnourished patients with HF were associated with increased risks of all-cause death (RR, 1.61, 95% CI, 1.40–1.85, I2 = 17%, P for heterogeneity = 0.29) and MACEs (RR, 2.12, 95% CI, 1.49–3.02, I2 = 87%, P for heterogeneity <0.0001), compared with those with normal nutritional status.

Conclusions

The CONUT score is associated with the clinical outcomes in patients with HF, and can be used as a screening tool of nutritional status in HF to improve prognosis.
Early-Onset Diabetes Mellitus in Chromosome 8p11.2 Deletion Syndrome Combined With Becker Muscular Dystrophy - A Case Report
Authors: Cao Conghui , Wang Xiaoli , Zhao Xiaojuan
Published: July 2022

Background

Chromosome 8p11.2 includes several key genes in development such as the FGFR1, ANK1, KAT6A, and SLC20A2 genes. Deletion of this fragment causes a contiguous gene syndrome. Currently, few cases of interstitial deletion of whole 8p11.2 have been reported. We report a rare case of 8p11.2 deletion syndrome with the unique phenotypes, presenting with early-onset diabetes.

Case Description

A 20-year-old man with a 1-year history of diabetes mellitus was admitted to the Endocrinology Clinic. Physical examination revealed the dysmorphic facial features, and broad and foreshortened halluces. Laboratory examination indicated spherocytosis anemia, and hypogonadotropic hypogonadism. Bone mineral density analysis showed decreased bone density in the lumbar vertebrae. Brain CT showed calcification. Whole-exome sequencing revealed a 7.05-Mb deletion in 8p11 containing 43 OMIM genes, and a large in-frame deletion of exons 48–55 in the DMD gene. Metformin was given to the patient after which his blood glucose was well controlled. HCG was injected subcutaneously and was supplemented with calcium and vitamin D, which led to an improvement in the patient’s quality of life.

Conclusion

We report a rare case of 8p11.2 deletion syndrome with unique phenotypes, and early-onset diabetes. It is challenging for endocrinologists to simultaneously reconcile a combination of these diseases across multiple disciplines. We discussed the influencing factors of early-onset diabetes in this patient and speculated that it was caused by complex interactions of known and unknown genetic backgrounds and environmental factors.
ACTH-independent Cushing’s syndrome due to ectopic endocrinologically functional adrenal tissue caused by a GNAS heterozygous mutation: a rare case of McCune–Albright syndrome accompanied by central amenorrhea and hypothyroidism: a case report and literature review
Authors: Takedani Kai , Yamamoto Masahiro , Tanaka Sayuri , Ishihara Shinichiro , Taketani Takeshi , Kanasaki Keizo
Published: July 2022

In a small number of cases, the development of ectopic residual adrenal lesions during embryogenesis causing Cushing’s syndrome due to the production of excess cortisol has been reported. A 29-year-old woman was admitted to our hospital for fatigue and recent amenorrhea. Her plasma ACTH was <1.5 pg/mL, and her serum cortisol was 21.4 pg/mL after the 8 mg dexamethasone suppression test, revealing the presence of ACTH-independent Cushing’s syndrome; however, her bilateral adrenal glands were atrophied. Abdominal CT revealed a 40-mm round tumor on the right renal hilum and remarkably accumulated 131I-labelled adosterol. CT and bone scintigraphy showed that 99mTc-methylene diphosphonate had accumulated in her dissymmetric skull at the right-frontoparietal region. The tumor on the right renal hilum was laparoscopically removed. Her cortisol levels rapidly decreased to below the normal range, and glucocorticoids were administered to rescue adrenal insufficiency. The resected tumor was yellowish in appearance and 4.5×3.0×2.8 cm in size. Immunohistochemical staining for SF-1, P450scc, CYP17A, CYP21A, and CYP11B1 indicated that this tumor produced cortisol. Exome sequencing analysis revealed that the GNAS heterozygous mutation (c.601C>T, p. Arg201Cys; accession number, NM_000516.5) was found in approximately 20% of the adrenal tumor sample. A mutation of GNAS, encoding the Gsα subunit that mediates GPCR signaling, causes the constitutive activation of adenylyl cyclase, resulting in hypersecretion of hormones regulated by the GPCR. GNAS mutation is one of the major genetic causes of cortisol-producing adrenal tumors independent of ACTH secretion. Considering the combination of GNAS mutation with one of the typical clinical triad characteristics, fibrous dysplasia of bone, we diagnosed this patient with McCune–Albright syndrome accompanied by ACTH-independent Cushing’s syndrome caused by an ectopic residual adrenal tumor due to GNAS mutation. This case highlights that GNAS involves a previously unknown pathological mechanism in which inhibition of the natural elimination of remnant tissue leads to ectopic endocrine hypersecretion.
Leucine zipper downregulated in cancer 1 may serve as a favorable prognostic biomarker by influencing proliferation, colony formation, cell cycle, apoptosis, and migration ability in hepatocellular carcinoma
Authors: Chen Huaping , Chen Siyuan , Chen Chen , Li Aifeng , Wei Zhixiao
Published: July 2022

Aims: Leucine zipper downregulated in cancer 1 (LDOC1) inhibits tumor growth in several cancers. However, the expression and function of LDOC1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we aimed to investigate how LDOC1 influenced tumor progression and the biological functions of HCC.

Methods: The transcription levels of LDOC1 were determined using the GEPIA and UALCAN online databases and a real-time polymerase chain reaction. Western blot and immunohistochemistry were used to validate the protein levels of LDOC1. The online Kaplan-Meier Plotter was applied for survival analysis. Then lentivirus transfection was used to construct LDOC1 exogenous overexpression cell lines. Proliferation, clone formation, cell cycle, apoptosis, and migration assays were performed with the LDOC1-upregulated Huh7 and Hep3B cell lines. The phosphorylated and total levels of AKT and mTOR were determined using a Western blot to explore the potential molecular mechanism of LDOC1.

Results: In the GEPIA and UALCAN analyses, LDOC1 was lowly expressed in tumors, had high expression in normal tissue samples (p < 0.05), and negatively correlated with tumor grade progression. The down-regulation of LDOC1 in HCC was validated with real-time polymerase chain reaction, Western blot, and immunohistochemistry (all p < 0.05). LDOC1 transcription levels were negatively associated with overall, progression-free, recurrence-free, and disease-specific survival (all p < 0.05). The functional experiments suggested that the overexpression of LDOC1 contributed to increased G1 and G2 stages in Huh7, while increased G2 stage in Hep3B, and decreased cell proliferation, clone formation, and migration, as well as increased the apoptosis rate compared with the control group (all p < 0.05). Furthermore, LDOC1 up-regulation reduced the p-AKT/AKT and p-mTOR/mTOR, which indicates an inactivation of the AKT/mTOR pathway.

Conclusion: The tumor-suppressor LDOC1 varied in HCC and non-HCC tissues, which can serve as a candidate prognostic biomarker. LDOC1 influenced survival by affecting proliferation, colony formation, cell cycle, apoptosis, and migration ability, which might be attributed to the AKT/mTOR inhibition in HCC.
Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts
Authors: Kingdom Rebecca , Wright Caroline F.
Published: July 2022

The same genetic variant found in different individuals can cause a range of diverse phenotypes, from no discernible clinical phenotype to severe disease, even among related individuals. Such variants can be said to display incomplete penetrance, a binary phenomenon where the genotype either causes the expected clinical phenotype or it does not, or they can be said to display variable expressivity, in which the same genotype can cause a wide range of clinical symptoms across a spectrum. Both incomplete penetrance and variable expressivity are thought to be caused by a range of factors, including common variants, variants in regulatory regions, epigenetics, environmental factors, and lifestyle. Many thousands of genetic variants have been identified as the cause of monogenic disorders, mostly determined through small clinical studies, and thus, the penetrance and expressivity of these variants may be overestimated when compared to their effect on the general population. With the wealth of population cohort data currently available, the penetrance and expressivity of such genetic variants can be investigated across a much wider contingent, potentially helping to reclassify variants that were previously thought to be completely penetrant. Research into the penetrance and expressivity of such genetic variants is important for clinical classification, both for determining causative mechanisms of disease in the affected population and for providing accurate risk information through genetic counseling. A genotype-based definition of the causes of rare diseases incorporating information from population cohorts and clinical studies is critical for our understanding of incomplete penetrance and variable expressivity. This review examines our current knowledge of the penetrance and expressivity of genetic variants in rare disease and across populations, as well as looking into the potential causes of the variation seen, including genetic modifiers, mosaicism, and polygenic factors, among others. We also considered the challenges that come with investigating penetrance and expressivity.
Integrated analysis of mRNA-single nucleotide polymorphism-microRNA interaction network to identify biomarkers associated with prostate cancer
Authors: Wang Zhiwen , Zhu Xi , Zhai Hongyun , Wang Yanghai , Hao Gangyue
Published: July 2022

Background: Prostate cancer is one of the most common malignancies among men worldwide currently. However, specific mechanisms of prostate cancer were still not fully understood due to lack of integrated molecular analyses. We performed this study to establish an mRNA-single nucleotide polymorphism (SNP)-microRNA (miRNA) interaction network by comprehensive bioinformatics analysis, and search for novel biomarkers for prostate cancer.

Materials and methods: mRNA, miRNA, and SNP data were acquired from Gene Expression Omnibus (GEO) database. Differential expression analysis was performed to identify differentially expressed genes (DEGs) and miRNAs (DEMs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, protein-protein interaction (PPI) analysis and expression quantitative trait loci (eQTL) analysis of DEGs were conducted. SNPs related to DEMs (miRSNPs) were downloaded from the open-source website MirSNP and PolymiRTS 3.0. TargetScan and miRDB databases were used for the target mRNA prediction of miRNA. The mRNA-SNP-miRNA interaction network was then constructed and visualized by Cytoscape 3.9.0. Selected key biomarkers were further validated using the Cancer Genome Atlas (TCGA) database. A nomogram model was constructed to predict the risk of prostate cancer.

Results: In our study, 266 DEGs and 11 DEMs were identified. KEGG pathway analysis showed that DEGs were strikingly enriched in focal adhesion and PI3K-Akt signaling pathway. A total of 60 mRNA-SNP-miRNAs trios were identified to establish the mRNA-SNP-miRNA interaction network. Seven mRNAs in mRNA-SNP-miRNA network were consistent with the predicted target mRNAs of miRNA. These results were largely validated by the TCGA database analysis. A nomogram was constructed that contained four variables (ITGB8, hsa-miR-21, hsa-miR-30b and prostate-specific antigen (PSA) value) for predicting the risk of prostate cancer.

Conclusion: Our study established the mRNA-SNP-miRNA interaction network in prostate cancer. The interaction network showed that hsa-miR-21, hsa-miR-30b, and ITGB8 may be utilized as new biomarkers for prostate cancer.
Identification of immune hub genes participating in the pathogenesis and progression of Vogt-Koyanagi-Harada disease
Authors: Wang Yiqi , Ju Yahan , Wang Jiajing , Sun Na , Tang Zhimin , Gao Huiqin , Gu Ping , Ji Jing
Published: July 2022

Background

Vogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disorder characterized by bilateral granulomatous uveitis. The objective of this study was to identify immune hub genes involved in the pathogenesis and progression of VKH disease.

Methods

High throughput sequencing data were downloaded from the Gene Expression Omnibus (GEO) and an immune dataset was downloaded from ImmPort. Immune differentially expressed genes (DEGs) were obtained from their intersection in the GEO and ImmPort datasets. Immune hub genes for VKH disease were selected through differential expression analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), protein-protein interaction (PPI) network, and clustering analyses. Confidence in the immune hub genes was subsequently validated using box plots and receiver operating characteristic (ROC) curves.

Results

A total of 254 DEGs were screened and after the intersection with ImmPort, 20 genes were obtained as immune DEGs. Functional enrichment analysis indicated that the key genes were mainly involved in several types of immune pathways (such as the lymphocyte mediated and leukocyte mediated immune responses, natural killer cell mediated cytotoxicity, and antigen binding) and immunodeficiency diseases. Following PPI network analysis, the top seven genes in cluster 1 were selected as potential immune hub genes in VKH. After evaluating the accuracy of the hub genes, one gene (GNLY) was excluded because its expression level was statistically similar in VKH patients and healthy controls. Finally, six immune hub genes, namely KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2 were identified as playing important roles in the occurrence and development of VKH disease.

Conclusion

Six immune hub genes (KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2) identified by our bioinformatics analyses may provide new diagnostic and therapeutic targets for VKH disease.
Chanalyzer: A Computational Geometry Approach for the Analysis of Protein Channel Shape and Dynamics
Authors: Raffo Andrea , Gagliardi Luca , Fugacci Ulderico , Sagresti Luca , Grandinetti Simone , Brancato Giuseppe , Biasotti Silvia , Rocchia Walter
Published: July 2022

Morphological analysis of protein channels is a key step for a thorough understanding of their biological function and mechanism. In this respect, molecular dynamics (MD) is a very powerful tool, enabling the description of relevant biological events at the atomic level, which might elude experimental observations, and pointing to the molecular determinants thereof. In this work, we present a computational geometry-based approach for the characterization of the shape and dynamics of biological ion channels or pores to be used in combination with MD trajectories. This technique relies on the earliest works of Edelsbrunner and on the NanoShaper software, which makes use of the alpha shape theory to build the solvent-excluded surface of a molecular system in an aqueous solution. In this framework, a channel can be simply defined as a cavity with two entrances on the opposite sides of a molecule. Morphological characterization, which includes identification of the main axis, the corresponding local radius, and the detailed description of the global shape of the cavity, is integrated with a physico-chemical description of the surface facing the pore lumen. Remarkably, the possible existence or temporary appearance of fenestrations from the channel interior towards the outer lipid matrix is also accounted for. As a test case, we applied the present approach to the analysis of an engineered protein channel, the mechanosensitive channel of large conductance.
A Cryptogenic Stroke Associated With Infective Endocarditis and Antiphospholipid Antibody Syndrome: Case Report and Literature Review
Authors: Chen Lei , Zhang Ping , Zhu Xuan , Zhang Minmin , Deng Benqiang
Published: July 2022

Introduction

Accurate definition of stroke etiology is crucial, as this will guide effective targets for treatment. Both antiphospholipid antibody syndrome (APS) and infective endocarditis (IE) can be independent risk factors for ischemic stroke in young adults. When an embolic stroke occurs with IE and APS simultaneously, the origin of the embolic source is difficult to identify.

Case Report

A 19-year-old man was admitted to the hospital for the onset of stroke. A diagnosis of APS accompanied by IE was made after a series of examinations. We identified aortic valve vegetation as the embolic source. Although both APS and IE can induce valve vegetation, we considered IE to be the primary cause according to the infective clues. Despite treatment with ampicillin, the patient's fever persisted, and surgical aortic valve replacement was performed urgently. The patient recovered without recurrence of stroke during the 1-year follow-up.

Conclusion

A considerable challenge for physicians is evaluating all the signs suggestive of embolic sources in acute stroke and identifying the primary etiology when there are multiple causes. Early diagnosis and surgical intervention for bicuspid aortic valve (BAV) vegetation complicated by acute stroke may yield favorable clinical results.
Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection
Authors: Sandler Carolina X. , Cvejic Erin , Valencia Braulio M. , Li Hui , Hickie Ian B. , Lloyd Andrew R.
Published: July 2022

Prospective cohort studies following individuals from acute infections have documented a prevalent post-infective fatigue state meeting diagnostic criteria for chronic fatigue syndrome (CFS) – that is, a post-infective fatigue syndrome (PIFS). The Dubbo Infection Outcomes Study (DIOS) was a prospective cohort following individuals from acute infection with Epstein-Barr virus (EBV), Ross River virus (RRV), or Q fever through to assessment of caseness for CFS designated by physician and psychiatrist assessments at 6 months. Previous studies in DIOS have revealed that functional genetic polymorphisms in both immunological (pro- and anti-inflammatory cytokines) and neurological (the purinergic receptor, P2X7) genes are associated with both the severity of the acute infection and subsequent prolonged illness. Principal components analysis was applied to self-report data from DIOS to describe the severity and course of both the overall illness and concurrent mood disturbance. Associations between demographics and acute infection characteristics, with prolonged illness course as well as the PIFS outcome were examined using multivariable statistics. Genetic haplotype-driven functional variations in the neuropeptide Y (NPY) gene previously shown to be associated with brain responses to stress, and to trait anxiety were also examined as predictors. The sample included 484 subjects (51% female, median age 32, IQR 19–44), of whom 90 (19%) met diagnostic criteria for CFS at 6 months. Participants with greater overall illness severity and concurrent mood disturbance in the acute illness had a more prolonged illness severity (HR = 0.39, 95% CI: 0.34–0.46, p < 0.001) and mood disturbance (HR = 0.36, 95% CI: 0.30–0.42, p < 0.001), respectively. Baseline illness severity and RRV infection were associated with delayed recovery. Female gender and mood disturbance in the acute illness were associated with prolonged mood disturbance. Logistic regression showed that the odds of an individual being diagnosed with PIFS increased with greater baseline illness severity (OR = 2.24, 95% CI: 1.71–2.94, p < 0.001). There was no association between the NPY haplotypes with overall illness severity or mood disturbance either during the acute illness phase or with prolonged illness (p > 0.05). Severe acute infective illnesses predicted prolonged illness, prolonged mood disturbance and PIFS. These factors may facilitate early intervention to manage both PIFS and mood disturbances.
The metabolic addiction of cancer stem cells
Authors: Sahoo Om Saswat , Pethusamy Karthikeyan , Srivastava Tryambak P. , Talukdar Joyeeta , Alqahtani Mohammed S. , Abbas Mohamed , Dhar Ruby , Karmakar Subhradip
Published: July 2022

Cancer stem cells (CSC) are the minor population of cancer originating cells that have the capacity of self-renewal, differentiation, and tumorigenicity (when transplanted into an immunocompromised animal). These low-copy number cell populations are believed to be resistant to conventional chemo and radiotherapy. It was reported that metabolic adaptation of these elusive cell populations is to a large extent responsible for their survival and distant metastasis. Warburg effect is a hallmark of most cancer in which the cancer cells prefer to metabolize glucose anaerobically, even under normoxic conditions. Warburg’s aerobic glycolysis produces ATP efficiently promoting cell proliferation by reprogramming metabolism to increase glucose uptake and stimulating lactate production. This metabolic adaptation also seems to contribute to chemoresistance and immune evasion, a prerequisite for cancer cell survival and proliferation. Though we know a lot about metabolic fine-tuning in cancer, what is still in shadow is the identity of upstream regulators that orchestrates this process. Epigenetic modification of key metabolic enzymes seems to play a decisive role in this. By altering the metabolic flux, cancer cells polarize the biochemical reactions to selectively generate “onco-metabolites” that provide an added advantage for cell proliferation and survival. In this review, we explored the metabolic-epigenetic circuity in relation to cancer growth and proliferation and establish the fact how cancer cells may be addicted to specific metabolic pathways to meet their needs. Interestingly, even the immune system is re-calibrated to adapt to this altered scenario. Knowing the details is crucial for selective targeting of cancer stem cells by choking the rate-limiting stems and crucial branch points, preventing the formation of onco-metabolites.
Risk factors for the progression from acute recurrent to chronic pancreatitis among children in China
Authors: Zeng Jingqing , Zhang Jiayu , Hu Yabin , Wang Xiumin , Deng Zhaohui
Published: July 2022

Background

Risk factors for progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children are poorly understood.

Aim

To summarize the clinical characteristics of children with ARP and CP, identify the risk factors of CP, and investigate the factors associated with rapid progression from initial onset of ARP to CP.

Methods

The following variables were included in the risk factor analysis: sex, age at onset, family history, pancreas or biliary tract structural abnormalities, and genetic variations. Univariate and multivariate logistic regression analyses were used to assess the risk factors of CP. The Kaplan–Meier curves of the ARP progression to CP for various risk factor groupings were constructed and compared using the log-rank test. The Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR) of progression to CP for each risk variable.

Results

In total, 276 children were studied, of whom 136 progressed to CP. Among them, 41 had pancreatic duct obstructive disease; 105 underwent genetic testing, of whom 68 were found to have genetic variations. Among the remaining 140 patients who did not progress to CP, 61 had biliary obstructions. Forty-three of these children underwent genetic testing, and 15 were found to have genetic variations. Risk factor analysis showed that children with gene mutations were at a higher risk of progressing to CP [odds ratio (OR) = 3.482; 95% confidence interval (CI): 1.444–8.398; P = 0.005]; children with pancreas divisum (PD) had a higher risk of CP than those without (OR = 8.665; 95% CI: 1.884, 9.851; P = 0.006). Further, children whose first ARP occurred at an older age might develop CP faster (HR = 1.070; 95% CI: 1.003, 1.141; P = 0.039). Children with gene mutations had a faster rate of progression to CP after onset than children without gene mutations (HR = 1.607; 95% CI: 1.024, 2.522; P = 0.039), PRSS1 gene mutations were more associated (P = 0.025). There was no difference in the rate of progression from ARP to CP in children with PD (P = 0.887); however, endoscopic retrograde cholangiopancreatography (ERCP) intervention delayed the progression to CP in ARP patients with PD (P = 0.033).

Conclusion

PRSS1 gene mutations and PD are key risk factors for ARP progression to CP in children. PD itself does not affect the disease progression rate, but therapeutic ERCP can be beneficial to patients with ARP with symptomatic PD and delay the progression to CP.
The Efficient Techniques for Non-Linear Fractional View Analysis of the KdV Equation
Authors: Khan Hassan , Khan Qasim , Tchier Fairouz , Singh Gurpreet , Kumam Poom , Ullah Ibrar , Sitthithakerngkiet Kanokwan , Tawfiq Ferdous
Published: July 2022

The solutions to fractional differentials equations are very difficult to investigate. In particular, the solutions of fractional partial differential equations are challenging tasks for mathematicians. In the present article, an extension to this idea is presented to obtain the solutions of non-linear fractional Korteweg–de Vries equations. The solutions comparison of the proposed problems is done via two analytical procedures, which are known as the Residual power series method (RPSM) and q-HATM, respectively. The graphical and tabular analysis are presented to show the reliability and competency of the suggested techniques. The comparison has shown the greater contact between exact, RPSM, and q-HATM solutions. The fractional solutions are in good control and provide many important dynamics of the given problems.