bluuebunny/crossref_metadata_2025 huggingface dataset:
Hubungan Pengkajian Nyeri Menggunakan CPOT Terhadap Perubahan Status Hemodinamik pada pasien di ICU
Authors: Gaghauna Eirene Eunike Meidiana , Santoso Bagus Rahmat
Published: December 2022

Masalah Nyeri merupakan suatu respon alami yang bersifat langsung terhadap suatu peristiwa atau kejadian yang tidak mengenakkan karena kerusakan jaringan, seperti proses penyakit atau tindakan pengobatan dan pembedahan ( Hayati, 2014 dalam Apriani et al, 2018). Munculnya nyeri pada pasien penurunan kesadaran disebabkan oleh penyakit akut dan banyaknya intervensi dan tindakan yang dilakukan di ICU seperti: operasi, trauma, tindakan invasif, perawatan luka dan perubahan posisi pada pasien (Sutari, 2014 dalam Apriani et al, 2018).Tujuan: penelitian ini untuk menganalisis hubungan pengkajian nyeri menggunakan CPOT terhadap perubahan status hemodinamik pada pasien.Metode: Desain penelitian ini adalah penelitian korelasi yang dilakukan analisis data statistik menggunakan Mann-Whitney. Lembar penilaian skala nyeri CPOT dan Lembar Observasi Status hemodinamik.Hasil: pengukuran tingkat nyeri menggunakan CPOT  berhubungan dengan perubahan status hemodinamik dengan kenaikan yang beragam tergantung tingkatan nyeri yang dirasakan oleh pasien.Kesimpulan: perlunya monitoring tingkat nyeri khususnya pada pasien yang menggunakan ventilator diruang Intensive care sebagai salah satu upaya monitoring status hemodinamik yang berpengaruh dalam perbaikan kondisi pasien di ICU. Kata Kunci: CPOT, Nyeri, Status Hemodinamik The Effect of Family Health Seek Behavior to the Outcome of Stroke Patient using National Institute of Health Stroke Scale (NIHSS) in Emergency Department Introduction: Pain is a natural response that is direct to an unpleasant event or event due to tissue damage, such as a disease process or treatment and surgery (Hayati, 2014 in Apriani et al, 2018). The emergence of pain in patients with decreased consciousness is caused by acute illness and the many interventions and actions carried out in the ICU such as: surgery, trauma, invasive procedures, wound care and position changes in patients (Sutari, 2014 in Apriani et al, 2018).Purpose: To analyze the relationship of pain assessment using CPOT to changes in hemodynamic status in patients.Results: The design of this research is correlation research which is analyzed statistical data using Mann-Whitney. CPOT pain scale assessment sheet and Hemodynamic Status Observation Sheet.Conclusion: the need for monitoring the level of pain, especially in patients who use a ventilator in the intensive care room as an effort to monitor hemodynamic status that affects the improvement of the patient's condition in the ICU Keywords: CPOT, Hemodynamic Status, Pain
PENGARUH MOBILISASI DINI TERHADAP PERISTALTIK USUS PADA PASIEN POST OP LAPARATOMI
Authors: Pramono Yosra Sigit , Agustini Meti
Published: December 2022

Latar Belakang: : Laparatomi merupakan pembedahan insisi menuju rongga abdomen dimana operasi yang dapat dilakukan dengan prosedur laparotomi pada bagian digestive antara lain herniotomi, gasterktomi, kolesisduodenostomi  hepatektomi, splenoktomi, appendiktomi, kolostomi. Pemulihan peristaltik usus yang lebih cepat disebabkan oleh adanya kegiatan mobilisasi dini di mana kegiatan mobilisasi tersebut akan berpengaruh pada sistem kardiovaskuler, pernafasan, dan metabolisme.

Tujuan : Mengidentifikasikan pengaruh mobilisasi dini terhadap peristaltik usus pada pasien post op laparatomi di Rumah Sakit Umum Ulin Banjarmasin

Metode: Pra Eksperimen dengan rancangan pretest dan posttest (one group pre-post test design). Sampel dalam penelitian berjumlah 14 orang, metode pengambilan data dilakukan secara non probability sampling yaitu Accidental Sampling

Hasil: Uji Paired Sample T-Test menunjukan p : 0.000 <  0.05 yang mengindikasikan ada pengaruh mobilisasi dini terhadap peristaltik usus pada pasien dengan post op laparatomi.

Kesimpulan:  ada pengaruh mobilisasi dini terhadap peristaltik usus pada pasien dengan post op laparatomi

                                                                        

Kata kunci: Laparatomi, Mobilisasi Dini, Peristaltik Usus
Hubungan Peran Orang Tua Dengan Sikap Remaja Usia 15 19 Tahun Dalam Mengambil Keputusan Pernikahan Dini Di SMKN 2 Simpang Empat Tahun 2021
Authors: Putra Farhandika
Published: December 2022

Latar Belakang: Pernikahan dini merupakan perkawinan dibawah umur yang target persiapannya belum dikatakan maksimal. Tujuan: penelitian bertujuan untuk mengetahui hubungan antara faktor sosial (peran) dengan sikap remaja usia 15-19 tahun dalam mengambil keputusan menikah muda. Metode: Rancangan penelitian ini menggunakan desain kuantitatif dengan cross sectional. Sampel dalam penelitian ini 100 responden dengan teknik simple random sampling. Hasil: Hasil penelitian ini didapatkan sebanyak 60 responden (60%) memiliki faktor sosial (peran) positif, dan sebanyak 56 responden (56%) memiliki sikap positif. Analisis dengan menggunakan uji Chi Square didapatkan hasil sig 0,007 (<0,05). Kesimpulan: dari penelitian ini, terdapat hubungan antara faktor sosial (peran) dengan sikap remaja dalam mengambil keputusan menikah muda. Disarankan untuk pihak sekolah SMKN 2 Simpang Empat dapat meningkatkan pengetahuan siswa tentang pengaruh menikah muda dengan cara memberikan edukasi sebagai upaya pencegahan untuk menikah muda.
HUBUNGAN PENGETAHUAN TERHADAP PENERAPAN POLA ASUH ORANG TUA PADA ANAK BERKEBUTUHAN KHUSUS STUDI LITERATUR
Authors: Devianto Aan
Published: December 2022

Latar Belakang: Anak Berkebutuhan Khusus (ABK) adalah anak yang memiliki perbedaan dengan anak-anak secara umum atau rata-rata anak seusianya, ABK diartikan sebagai individu-individu yang mempunyai karakteristik yang berbeda dari individu lainnya atau dipandang tidak normal oleh masyarakat pada umumnya sehingga memerlukan perlakuan khusus dalam memenuhi kebutuhannya. Tujuan: Menjelaskan pengetahuan dengan pola asuh orang tua terhadap Anak Berkebutuhan Khusus (ABK) berdasarkan telaah kritis jurnal. Metode: Penelitian ini menggunakan metode studi literatur yang menganalisis 6 artikel yang telah dipublikasikan melalui mesin pencari Google Schoolar, EBSCO, dan Portal Garuda dengan menyeleksi sebanyak 19.239 artikel dengan kata kunci pengetahuan serta pola asuh orang tua pada anak berkebutuhan khusus. Pencarian dibatasi pada tahun 2016-2020 yang dapat diaksess free full text. Artikel tersebut selanjutnya dilakukan proses identifikasi, skrinning, eligible, dan inklusi artikel. Hasil: Pengetahuan yang memadai akan berdampak pada keterampilan ibu dalam memberikan pola asuh yang baik dan benar sehingga anak berkebutuhan khusus tetap dapat tumbuh dan berkembang ditengah keterbatasan yang mereka alami, dan dari 6 artikel pada penelitian ini di dapatkan adanya hubungan antara pengetahuan dan pola asuh ibu dalam menghadapi anak berkebutuhan khusus. Kesimpulan: Ada hubungan yang signifikan antara pengetahuan dan pola asuh ibu dalam menghadapi anak berkebutuhan khusus.
HUBUNGAN KARAKTERISTIK DENGAN KEPATUHAN PERAWAT DALAM PELAKSANAAN TRIAGE COVID DI IGD
Authors: Aprilia Hanura
Published: December 2022

Background: Triage of patients with Covid-19 is a new thing for nurses who work in the Emergency Department. The implementation of this triage must be carried out in accordance with the guidelines or procedures that have been set, but there are nurses who have not complied with it. This non-compliance varies based on the characteristics of nurses, namely age, gender, education level and length of work of nurses. Objective: This study aims to determine the relationship between age, gender, level of education, length of work and nurse compliance in the implementation of triage for Covid 19 patients in the ER Banjarmasin Islamic Hospital. Method: This study used a cross sectional design. The population was all nurses who served in the ER taken with a total population technique of 33 people. Data analysis using Spearman Rank. Result: The results of the study found that there was a relationship between age and nurse compliance in the implementation of triage for Covid 19 patients with a value of = 0.004 and the strength of the relationship was moderate (r = 0.492), there was a relationship between gender and nurse compliance with a value of = 0.000 and the strength of a strong relationship (r = 0.686), there is a relationship between the level of education and nurse compliance with a value of = 0.036 and the strength of the relationship is moderate (r = 0.367) and there is a relationship between length of work and nurse compliance with a value of = 0.001 and the strength of a strong relationship (r = 0.563). Conclusion: Nurses who have not complied should be given training or socialization about COVID-19 triage.
АВТОРСКИЕ ВОСПОМИНАНИЯ О ВАЖНЫХ СОБЫТИЯХ ЖИЗНИ
Authors: Дурасов Геннадий Петрович
Published: December 2022

Воспоминания известного писателя, этнографа, фольклориста, агиографа и коллекционера Геннадия Петровича Дурасова включают в себя эскизы важнейших эпизодов жизни, связанных с его научно-исследовательской и коллекционной деятельностью. Описаны тесные связи с Рублевским музеем, коллективом его реставраторов в 1970-е – 1980 е годы, переданы экспедиционная атмосфера тех лет, множество важных встреч и знакомств, включение автора в реставрационную и коллекционную деятельность, неожиданное освоение новых профессий и навыков. Отдельная тема – судьба архивов, домашних коллекций, понимание важности коллекционной деятельности. Автор не случайно видит себя музееведом, об этом говорят его теснейшие творческие связи с отдельными музеями страны в Каргополе, Архангельске, Москве, его плодотворное участие в деятельности Всероссийского общества охраны памятников истории и культуры как лектора, корреспондента, практика.
The memoirs of the famous writer, ethnographer, folklorist, hagiographer and collector Gennady Petrovich Durasov include sketches of the most important episodes of life associated with his research and collection activities. Close ties with the Rublevsky Museum and a team of its restorers in the 1970s–1980s are described, the expeditionary atmosphere of those years, many important meetings and acquaintances, the inclusion of the author in restoration and collection activities, the unexpected acquisition of new professions and skills are conveyed. A separate topic is the fate of archives, home collections, understanding the importance of collecting activities. It is not by chance that the author sees himself as a museologist, this is evidenced by his closest creative ties with individual museums of the country in Kargopol, Arkhangelsk, Moscow, his fruitful participation in the activities of the All-Russian Society for the Protection of Historical and Cultural Monuments as a lecturer, correspondent, and practitioner.
Identification and validation of critical genes with prognostic value in gastric cancer
Authors: Dong Ningxin , Ma Xiaolong , Shen Jing , Zheng Yunlu , Li Guiyuan , Zheng Shaoqiang , Huang Xiaoyi
Published: December 2022

Background: Gastric cancer (GC) is a digestive system tumor with high morbidity and mortality rates. Molecular targeted therapies, including those targeting human epidermal factor receptor 2 (HER2), have proven to be effective in clinical treatment. However, better identification and description of tumor-promoting genes in GC is still necessary for antitumor therapy.

Methods: Gene expression and clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Last absolute shrinkage and selection operator (LASSO) Cox regression were applied to build a prognostic model, the Prognosis Score. Functional enrichment and single-sample gene set enrichment analysis (ssGSEA) were used to explore potential mechanisms. Western blotting, RNA interference, cell migration, and wound healing assays were used to detect the expression and function of myosin light chain 9 (MYL9) in GC.

Results: A four-gene prognostic model was constructed and GC patients from TCGA and meta-GEO cohorts were stratified into high-prognosis score groups or low-prognosis score groups. GC patients in the high-prognosis score group had significantly poorer overall survival (OS) than those in the low-prognosis score groups. The GC prognostic model was formulated as PrognosisScore = (0.06 × expression of BGN) - (0.008 × expression of ATP4A) + (0.12 × expression of MYL9) - (0.01 × expression of ALDH3A1). The prognosis score was identified as an independent predictor of OS. High expression of MYL9, the highest weighted gene in the prognosis score, was correlated with worse clinical outcomes. Functional analysis revealed that MYL9 is mainly associated with the biological function of epithelial-mesenchymal transition (EMT). Knockdown of MYL9 expression inhibits migration of GC cells in vitro.

Conclusion: We found that PrognosisScore is potential reliable prognostic marker and verified that MYL9 promotes the migration and metastasis of GC cells.
Nurse-patient communication on the south Texas border: Negotiating language and cultural discordance during the COVID-19 pandemic
Authors: Gonzalez Ariadne A. , Davis Stuart
Published: December 2022

Throughout the COVID-19 pandemic, medical professionals have experienced unforeseen and often under-discussed hurdles to meeting the surging demand for patient care. In particular, practitioners in under-resourced areas have faced enormous barriers when attempting to adequately address the swell in demand. Analyzing these tensions through the growing body of literature on patient communication during the COVID-19 pandemic, this article centers the work experiences of registered nurses serving on the frontlines of the South Texas-Mexico border of Laredo, Texas. Using a qualitative method of semi-structured and in-depth interviews with nurses working inside two COVID-19 hospital units, our thematic analysis reveals the work challenges generated by language discordance and cultural differences experienced between travel nurses, patients, and their families. Our findings further exposed the added workload and work strain generated from the language and cultural barriers experienced by local bilingual nurses, tracking how during a global pandemic such barriers place material strain on nurses' workload.
E-mental health implementation in inpatient care: Exploring its potential and future challenges
Authors: Van Assche Eva , Bonroy Bert , Mertens Marc , Van den Broeck Lore , Desie Kimberly , Bolinski Felix , Amarti Khadicha , Kleiboer Annet , Riper Heleen , Van Daele Tom
Published: December 2022

Background

There is a great evidence base today for the effectiveness of e-mental health, or the use of technology in mental healthcare. However, large-scale implementation in mental healthcare organisations is lacking, especially in inpatient specialized mental healthcare settings.

Aim

The current study aimed to gain insights into the factors that promote or hinder the implementation of e-mental health applications on organisational, professional and patient levels in Belgium.

Methods

Four Belgian psychiatric hospitals and psychiatric departments of general hospitals invited their professionals and patients to use Moodbuster, which is a modular web-based platform with a connected smartphone application for monitoring. The platform was used in addition to treatment as usual for three to four months. The professionals and patients completed pre- and post-implementation questionnaires on their reasons to participate or to decline participation and experiences with the Moodbuster platform.

Results

Main reasons for the organisations to participate in the implementation study were a general interest in e-mental health and seeing it is a helpful add-on to regular treatment. The actual use of Moodbuster by professionals and patients proved to be challenging with only 10 professionals and 24 patients participating. Implementation was hindered by technical difficulties and inpatient care specific factors such as lack of structural facilities to use e-mental health and patient-specific factors. Professionals saw value in using e-mental health applications for bridging the transition from inpatient to outpatient care. Twenty-two professionals and 31 patients completed the questionnaire on reasons not to participate. For the patients, lack of motivation because of too severe depressive symptoms was the most important reason not to participate. For professionals, it was lack of time and high workload.

Conclusions

The current implementation study reveals several important barriers to overcome in order to successfully implement e-mental health in inpatient psychiatric care.
Effect of Codonopsis Radix and Polygonati Rhizoma on the regulation of the IRS1/PI3K/AKT signaling pathway in type 2 diabetic mice
Authors: Mao Yong-po , Song Yi-ming , Pan Sheng-wang , Li Ning , Wang Wen-xiang , Feng Bin-bin , Zhang Jian-hai
Published: December 2022

Objective

Codonopsis Radix and Polygonati Rhizoma (CRPR) has a good hypoglycemic effect. The aims of the present study were to investigate the effect of CRPR on high-fat/high-sugar diet (HFHSD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) mice as well as to investigate the involved mechanism.

Methods

A T2DM mouse model was generated by combining HFHSD and STZ. After the model was established, normal and model groups received the same volume of normal saline intragastrically, and the negative control group was treated with metformin (200 mg/kg·BW). The low, medium, and high CRPR groups received four consecutive weeks of oral gavage with CRPR doses of 2.5, 5, and 10 g/kg·BW, respectively, during the course of the study. Body weight and fasting blood glucose (FBG) were measured on a weekly basis. Enzyme-linked immunosorbent assay (ELISAs) were used to evaluate the serum and liver samples. Hematoxylin and eosin (H&E) staining was utilized to observe the pathological status of the liver and pancreas. Western blot (WB) analysis was performed to evaluate the protein expression levels of PI3K, p-PI3K, AKT, and p-AKT.

Results

Compared to model mice, each treatment group had significantly elevated levels of FBG, total cholesterol (TC), and triacylglycerol (TG) (P<0.01 and P<0.05, respectively). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced in the treatment groups compared to the model group (P<0.01). Compared to the model group, fasting insulin (FINS) levels were elevated in all groups of CRPR (P<0.05), and there were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) in both the low-dose and high-dose CRPR groups (P<0.05). H&E staining indicated that CRPR treatment reduced organ enlargement, improved liver lipid accumulation, and repaired islet injury in T2DM mice. Moreover, WB analysis demonstrated that all CRPR groups significantly upregulated the protein expression of IRS1, p-GSK3β, PI3K, p-Akt and p-FOXO1(P<0.05) as well as significantly downregulated p-IRS1 and FOXO1 protein expression (P<0.05).

Conclusion

The present study demonstrated that CRPR effectively improves the metabolic disturbance of lipids, repairs damaged liver tissues, repairs damaged pancreatic tissues, and reduces insulin resistance (IR) in T2DM mice. The mechanism of action may be associated with upregulation of the IRS1/PI3K/AKT signaling pathway and inhibition of IRS1 phosphorylation.
The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus
Authors: Voss Lasse F. , Howarth Amanda J. , Wittenborn Thomas R. , Hummelgaard Sandra , Juul-Madsen Kristian , Kastberg Kristian S. , Pedersen Mathias K. , Jensen Lisbeth , Papanastasiou Anastasios D. , Vorup-Jensen Thomas , Weyer Kathrin , Degn Søren E.
Published: December 2022

Introduction

Many autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development.

Methods

We blocked the GC pathway by knocking out the transcription factor Bcl-6 in GC B cells, leaving the extrafollicular pathway intact. We tested the impact of this intervention in two murine models of systemic lupus erythematosus (SLE): a pharmacological model based on chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and 564Igi autoreactive B cell receptor knock-in mice. The B cell intrinsic effects were further investigatedin vitroand in autoreactive mixed bone marrow chimeras.

Results

GC block failed to curb autoimmune progression in the R848 model based on anti-dsDNA and plasma cell output, superoligomeric DNA complexes, and immune complex deposition in glomeruli. The 564Igi model confirmed this based on anti-dsDNA and plasma cell output.In vitro, loss of Bcl-6 prevented GC B cell expansion and accelerated plasma cell differentiation. In a competitive scenarioin vivo, B cells harboring the genetic GC block contributed disproportionately to the plasma cell output.

Discussion

We identified the extrafollicular pathway as a key contributor to autoimmune progression. We propose that therapeutic targeting of low quality and poorly controlled extrafollicular responses could be a desirable strategy to curb autoreactivity, as it would leave intact the more stringently controlled and high-quality GC responses providing durable protection against infection.
Impact of hepatic steatosis on treatment response of autoimmune hepatitis: A retrospective multicentre analysis
Authors: Liu Peiyan , Li Mingkai , Zhao Lili , Yu Hongsheng , Zhao Chang , Chen Jianning , Shi Ruifang , Zhou Li , Zhou Qi , Wu Bin , Li Jia
Published: December 2022

Background

There is a paucity of data on whether steatosis impacts autoimmune hepatitis (AIH) treatment response. We aimed to evaluate the influence of baseline steatosis on the biochemical response, fibrosis progression, and adverse longterm outcomes of AIH.

Methods

Steatosis was diagnosed by a controlled attenuation parameter (CAP) ≥ 248 dB / m. Only patients who underwent immunosuppressive therapy with available liver histological material at diagnosis and qualified CAP within seven days of the liver biopsy were included. Univariate and multivariate analyses were subsequently conducted.

Results

The multicentre and retrospective cohort enrolled 222 subjects (88.3% female, median age 54 years, median follow-up 48 months) in the final analysis, and 56 (25.2%) patients had hepatic steatosis. Diabetes, hypertension, and significant fibrosis at baseline were more common in the steatosis group than in the no steatosis group. After adjusting for confounding factors, hepatic steatosis was an independent predictor of insufficient biochemical response (OR: 8.07) and identified as an independent predictor of long-term adverse outcomes (HR: 4.07). By subgroup multivariate analysis (different degrees of steatosis, fibrosis, and prednisone dose), hepatic steatosis independently showed a relatively stable correlation with treatment response. Furthermore, in contrast to those without steatosis, a significant increase in liver stiffness (LS) was observed in patients with steatosis (4.1%/year vs. -16%/year, P < 0.001).

Conclusions

Concomitant hepatic steatosis was significantly associated with poor response to treatment in AIH patients. Routine CAP measurements are therefore essential to guide the management of AIH.
Duration biased distribution of clinical and immunological phenotypes in active SLE
Authors: Yan Qingran , Liu Bei , Yang Minjie , Li Qianqian , Wang Jieying , Li Ting , Lu Liangjing
Published: December 2022

Introduction

This study is aimed to map the clinical and immunological features of active lupus patients with different disease duration.

Methods

For clinical phenotype analysis, we enriched eligible medical records with active SLE (SLEDAI-2k≥8) from the Renji Lupus registry, a single-center database of hospitalized SLE patients with standard care, which covered national-wide patients. Patients with repeated hospitalization records in this enrichment were analyzed longitudinally as validation for the cross-sectional study above.

Results

We enriched a total of 1313 eligible records on active SLE (SLEDAI-2k≥8) for cross-sectional analysis. Stratified into four groups by a 5-year interval of disease duration, these active SLE patients showed a significantly shifting clinical phenotype along with the duration (ascending nephritis, pulmonary hypertension and descending fever, cutaneous symptoms, arthritis, and neuropsychiatric manifestations), especially in stratifications with disease onset age ≤ 45 years old. A longitudinal analysis of 55 patients with repeated hospitalizations for active lupus showed a similar trend. In the cross-sectional study of 222 records with full information on serology and lymphocyte subsets, peripheral B cell proportion, anti-dsDNA antibody, and serum IgG/IgM negatively correlated with duration, while CD8+ T cell proportion was positively correlated (P values, 0.029-4.8×10-17), which were supported by the sensitivity analysis in patient subgroups according to disease onset age and recent treatment. Multivariate linear regression identified duration as the only significant associator with both B cell and CD8+ T cell proportion (P values, 8.9×10-8 and 7.6×10-5, respectively). These duration biased immune phenotypes were highly consistent with the longitudinal observation in 14 patients with repeated hospitalizations.

Conclusions

Both clinical and immunological features of active SLE are significantly duration biased distributed, which merits further investigations in the evolution of SLE pathogenesis.
T cell repertoire profiling in allografts and native tissues in recipients with COVID–19 after solid organ transplantation: Insight into T cell–mediated allograft protection from viral infection
Authors: Fu Jianing , Rust Dylan , Fang Zhou , Jiao Wenyu , Lagana Stephen , Batal Ibrahim , Chen Bryan , Merl Sarah , Jones Rebecca , Sykes Megan , Weiner Joshua
Published: December 2022

Introduction

The effects of the SARS-CoV-2 virus on the body, and why the effects are more severe in certain patients, remain incompletely understood. One population of special interest is transplant recipients because of their immunosuppressed state. Understanding the pathophysiology of graft dysfunction in transplant patients with the COVID-19 viral syndrome is important for prognosticating the risk to the graft as well as understanding how best to prevent and, if necessary, treat graft injury in these patients.

Methods

We analyzed multiple types of solid organ transplant recipients (liver, kidney, heart or lung) at our institution who died from SARS-CoV-2 and underwent autopsy (n = 6) or whose grafts were biopsied during active SARS-CoV-2 infection (n = 8). Their serum inflammatory markers were examined together with the histological appearance, viral load, and TCR repertoire of their graft tissue and, for autopsy patients, several native tissues.

Results

Histology and clinical lab results revealed a systemic inflammatory pattern that included elevated inflammatory markers and diffuse tissue damage regardless of graft rejection. Virus was detected throughout all tissues, although most abundant in lungs. The TCR repertoire was broadly similar throughout the tissues of each individual, with greater sharing of dominant clones associated with more rapid disease course. There was no difference in viral load or clonal distribution of overall, COVID-associated, or putative SARS-CoV-2-specific TCRs between allograft and native tissue. We further demonstrated that SARSCoV-2-specific TCR sequences in transplant patients lack a donor HLArestricted pattern, regardless of distribution in allograft or native tissues,suggesting that recognition of viral antigens on infiltrating recipient cells can effectively trigger host T cell anti-viral responses in both the host and graft.

Discussion

Our findings suggest a systemic immune response to the SARS-CoV-2 virus in solid organ transplant patients that is not associated with rejection and consistent with a largely destructive effect of recipient HLA-restricted T cell clones that affects donor and native organs similarly.
Case Report: Isolated facial and trigeminal nerve palsy without ataxia in anti-GQ1b antibody syndrome secondary to Mycoplasma pneumonia
Authors: Deng Shuwen , Yin Lihong , Lu Wei , Ouyang Song , Yin Weifan
Published: December 2022

The presence of anti-GQ1b antibodies in serum or cerebrospinal fluid is a diagnostic indicator of the Miller–Fisher variant of Guillain–Barré syndrome (GBS), whereas anti-GQ1b antibody syndrome is rarely presented as acute bilateral pain in the cheeks and masticatory muscle fatigue without ophthalmoplegia, ataxia, or limb weakness. Here, we report a case of a female patient diagnosed with GBS characterized only by the involvement of the facial and trigeminal nerves who was positive for serum anti-GQ1b antibodies secondary to Mycoplasma pneumoniae infection. The patient was treated with macrolide antibiotics and neurotrophic drugs, and her symptoms were significantly alleviated after 1 month. This case indicates a new clinical presentation of GBS and anti-GQ1b antibody syndrome with a differential diagnosis of multiple cranial nerve damage of which neurological physicians should be aware. Positive anti-GQ1b antibodies secondary to infection were observed in this case, and antibiotic treatment resulted in a favorable prognosis. The specific underlying mechanism requires further investigation.
Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination
Authors: Koers Jana , Marsman Casper , Steuten Juulke , Tol Simon , Derksen Ninotska I. L. , ten Brinke Anja , van Ham S. Marieke , Rispens Theo
Published: December 2022

The generation of high-affinity antibodies requires an efficient germinal center (GC) response. As differentiating B cells cycle between GC dark and light zones they encounter different oxygen pressures (pO2). However, it is essentially unknown if and how variations inpO2affect B cell differentiation, in particular for humans. Using optimizedin vitrocultures together with in-depth assessment of B cell phenotype and signaling pathways, we show that oxygen is a critical regulator of human naive B cell differentiation and class switch recombination. Normoxia promotes differentiation into functional antibody secreting cells, while a population of CD27++B cells was uniquely generated under hypoxia. Moreover, time-dependent transitions between hypoxic and normoxicpO2during culture - reminiscent ofin vivoGC cyclic re-entry - steer different human B cell differentiation trajectories and IgG class switch recombination. Taken together, we identified multiple mechanisms trough which oxygen pressure governs human B cell differentiation.
Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration
Authors: Huang Tingting , OuYang XIaoxiao , Li Jiwei , Shi Bingbing , Shan Zhengda , Shi Zhiyuan , Yang Zhangru
Published: December 2022

Background

The F-box and WD repeat domain containing (FBXW) family of SCF E3 complexes has 10 members that are responsible for ubiquitination and degradation of substrate proteins involved in cell cycle regulation and tumorigenesis. Among them, FBXW1 (also called b-TrCP1/BTRC) and FBXW7 are the central proteins in this category. However, there is still a lack of elaborate exploration of the contribution of FBXW family members, especially FBXW1 and FBXW7, in various tumor types.

Methods

In this present study, we preliminarily analyzed the genetic structure characteristics of the FBXW family, and systematically investigated their expression patterns and clinical correlations based on the TCGA pan-cancer data. Survival analysis of FBXWs was also conducted through the Kaplan-Meier method. In addition, we assessed their immune infiltration level through immune-related algorithms like Timer and xCell.

Results

There were obvious genetic heterogeneity and different clinical traits in FBXW family members. Moreover, we found that FBXW family genes may be useful in predicting prognosis and therapeutic efficacy using survival analysis. In addition, the immune infiltration of FBXW family was also clearly illustrated in this study. The results showed these genes were closely involved in immune components such as immune score, immune subtypes, tumor-infiltrating lymphocytes and immune checkpoints. Notedly, FBXW1 as an oncogene and FBXW7 as a tumor suppressor gene also show opposite relationships on immune cells.

Conclusion

Our results provided valuable strategies to guide the therapeutic orientation concerning the role of FBXW family genes in cancer.
Methylation changes induced by a glycodendropeptide immunotherapy and associated to tolerance in mice
Authors: Núñez Rafael , Rodríguez María J. , Lebrón-Martín Clara , Martín-Astorga María del Carmen , Palomares Francisca , Ramos-Soriano Javier , Rojo Javier , Torres María J. , Cañas José Antonio , Mayorga Cristobalina
Published: December 2022

Introduction

Allergen-specific immunotherapy (AIT) is applied as treatment to rise tolerance in patients with food allergies. Although AIT is thoroughly used, the underlying epigenetic events related to tolerant induction are still unknown. Thus, we aim to investigate epigenetic changes that could be related to tolerance in dendritic cells (DCs) from anaphylactic mice to lipid transfer proteins, Pru p 3, in the context of a sublingual immunotherapy (SLIT) with a glycodendropeptide (D1ManPrup3) that has demonstrated tolerant or desensitization responses depending on the treatment dose.

Methods

Changes in DNA methylation in CpG context were determined comparing Sensitized (Antigen-only) animals and two groups receiving SLIT with the D1ManPrup3 nanostructure (D1ManPrup3-SLIT): Tolerant (2nM D1ManPrup3) and Desensitized (5nM D1ManPrup3), against anaphylactic animals. DNA from lymph nodes-DCs were isolated and then, Whole Genome Bisulphite Sequencing was performed to analyze methylation.

Results

Most differentially methylated regions were found on the area of influence of gene promoters (DMPRs). Compared to the Anaphylactic group, the highest value was found in Desensitized mice (n = 7,713 DMPRs), followed by Tolerant (n = 4,091 DMPRs) and Sensitized (n = 3,931 DMPRs) mice. Moreover, many of these epigenetic changes were found in genes involved in immune and tolerance responses (Il1b, Il12b, Il1a, Ifng, and Tnf) as shown by functional enrichment (DCs regulation, B cell-mediated immunity, and effector mechanisms).

Discussion

In conclusion, different doses of D1ManPrup3-SLIT induce different DNA methylation changes, which are reflected in the induction of distinct responses, tolerance, or desensitization.
Influence of patch size on hydrodynamic flow in submerged aquatic vegetation
Authors: Matsumura K. , Nakayama K. , Matsumoto H.
Published: December 2022

Blue carbon, or carbon dioxide captured and stored by submerged aquatic vegetation (SAV) in ecosystems, has been attracting attention as a measure to mitigate climate change. Since the scale of SAV meadows is smaller than that of topography length scale, with the former often occurring in patches, the flexibilities of SAV motion induce complicated interactions with water flows and make it difficult to estimate carbon sequestration rates. Therefore, this study aims to clarify the influences of SAV patches on water flows and mass transport using laboratory experiments and numerical simulations. An SAV model was successfully applied to analyze the results of laboratory experiments, revealing good agreement and showing that the size of an SAV patch significantly affects the water flows. The extent to which the patch occupies the channel width was revealed to be the most substantial factor in controlling carbon absorption by SAV, and deflection was found to be another significant factor. Implementing global warming countermeasures is a critical goal of climate change mitigation, so our study outcome is expected to be helpful for improving and promoting blue carbon as a negative emission strategy.
Inferring individual marine migration from otolith ecogeochemical signatures of a wide-ranging fish
Authors: Hanson Nora , Ounsley James , Middlemas Stuart J. , Gilbey John , Todd Christopher D.
Published: December 2022

Despite technical advances in archival tag attachment and functional longevity, long-term tracking of individuals of some fish species remains prohibitively difficult. Here we combined high resolution stable isotope sampling of otoliths, genetic assignment, growth increment analyses and a simple movement model to inform a hidden Markov model of the location of individual wild Atlantic salmon (Salmo salar L.) at sea. The model provided a reconstruction of North Atlantic migration for a species which is extremely difficult to track throughout its marine life-stage. We show that plausible emigration and return migration patterns can be achieved from wild fish. Simulations of simplified northward and westward movement patterns in the North Atlantic were used to quantify precision and accuracy of the model which differed between these two directional scenarios. Because otolith-derived migratory information does not rely on capture, release and subsequent recapture of the individual, this can be retrieved from any fish. Thus these techniques offer a powerful tool for improving our understanding of the processes that govern movement and survival of individual fish during a protracted and largely unobservable life-stage in the oceanic environment.
Modifying aluminum phthalocyanine with quantum dots to promote cellular uptake and enhance the efficacy of anticancer photodynamic therapy
Authors: Lei Li , Dai Bin , Han Ting , Zhou Cheng , Gong Zhao , Zhang Ping
Published: December 2022

Photodynamic therapy (PDT) is regarded as an alternative anti-tumor therapy which involves the administration of photosensitizers (PSs) and irradiation with specific light. However, conventional PDT therapy has been limited to the efficiency of PS delivery. A nanocarrier system could provide an effective platform for PS delivery and improve the efficiency of antitumor PDT. In this article, we prepared a complex consisting of aluminum phthalocyanine (AlPcS) and CdSe/CdZnS core-shell structure QDs and investigated the interaction between the complex and tumor cells. A more significant internalization of the conjugation was observed compared to free AlPcS via confocal fluorescence imaging. The tumor cells exhibited an obvious apoptotic trend after QD–AlPcS-mediated PDT.
Risk for excessive anticoagulation during hemodialysis is associated with type of vascular access and bedside coagulation testing: Results of a cross-sectional study
Authors: De Troyer Marijke , Wissing Karl Martin , De Clerck Dieter , Cambier Marie-Laure , Robberechts Tom , Tonnelier Annelies , François Karlien
Published: December 2022

Background

Recommendations and practice patterns for heparin dosing during hemodialysis show substantial heterogeneity and are scantly supported by evidence. This study assessed the variability in unfractionated heparin (UFH) dosing during hemodialysis and its clinical and biological anticoagulatory effects, and identified explanatory factors of heparin dosing.

Methods

Cross-sectional study assessing UFH dosing, coagulation tests – activated partial thromboplastin time (aPTT) and activated clotting time (ACT) before dialysis start, 1 h after start and at treatment end (4 h) – and measurement of residual blood compartment volume of used dialyzers.

Results

101 patients, 58% male, with a median dialysis vintage of 33 (6–71) months received hemodialysis using a total UFH dose of 9,306 ± 4,079 (range 3,000–23,050) IU/session. Use of a dialysis catheter (n = 56, 55%) was associated with a 1.4 times higher UFH dose (p < 0.001) irrespective of prior access function. aPTT increased significantly more than ACT both 1 h and 4 h after dialysis start, independent of the dialysis access used. 53% of patients with catheter access and ACT ratio < 1.5, 1 h after dialysis start had simultaneous aPTT ratios > 2.5. Similar findings were present at 1 h for patients with AVF/AVG and at dialysis end for catheter use. No clinically significant clotting of the extracorporeal circuit was noted during the studied sessions. Dialyzer’s blood compartment volume was reduced with a median of 9% (6–20%) without significant effect of UFH dose, aPTT or ACT measurements and vascular access type.

Conclusion

UFH dose adaptations based on ACT measurements frequently result in excessive anticoagulation according to aPTT results. Higher doses of UFH are used in patients with hemodialysis catheters without evidence that this reduces dialyzer clotting.
Psychometric evaluation of a national exam for clinical undergraduates
Authors: Han Yuting , Jiang Zhehan , Ouyang Jinying , Xu Lingling , Cai Ting
Published: December 2022

Background

As a high-stake national-level examination administrated before students’ clerkship in China, the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU) has received much attention from the relevant educational departments and society at large. Investigating SCTCMU’s validity and reliability is critical to the national healthcare profession education.

Materials and methods

Raw responses from SCTCMU, answered by 44,332 examines of 4th-year undergraduate medical students on 300 multiple-choice items, were used to evaluate the quality of the exam via psychometric methods based on item response theory (IRT). The core assumptions and model-data fit of IRT models were evaluated, as well as the item properties and information functions.

Results

The IRT models were fitted to the observed assessment data, where all the required assumptions were met. The IRT analysis showed that most items had acceptable psychometric properties, and the passing score was located close to the lowest measurement error computed from the model outcomes.

Conclusion

The proposed modern psychometric method provides a practical and informative approach to calibrating and analyzing medical education assessments. This work showcases a realistic depiction of the IRT analysis process and therefore facilitates the work of applied researchers wanting to conduct, interpret, and report IRT analyses on medical assessments.
Reliability of CD44, CD24, and ALDH1A1 immunohistochemical staining: Pathologist assessment compared to quantitative image analysis
Authors: Yaghjyan Lusine , Heng Yujing J. , Baker Gabrielle M. , Bret-Mounet Vanessa , Murthy Divya , Mahoney Matt B. , Mu Yi , Rosner Bernard , Tamimi Rulla M.
Published: December 2022

Background

The data on the expression of stem cell markers CD44, CD24, and ALDH1A1 in the breast tissue of cancer-free women is very limited and no previous studies have explored the agreement between pathologist and computational assessments of these markers. We compared the immunohistochemical (IHC) expression assessment for CD44, CD24, and ALDH1A1 by an expert pathologist with the automated image analysis results and assessed the homogeneity of the markers across multiple cores pertaining to each woman.

Methods

We included 81 cancer-free women (399 cores) with biopsy-confirmed benign breast disease in the Nurses’ Health Study (NHS) and NHSII cohorts. IHC was conducted with commercial antibodies [CD44 (Dako, Santa Clara, CA, USA) 1:25 dilution; CD24 (Invitrogen, Waltham, MA, USA) 1:200 dilution and ALDH1A1 (Abcam, Cambridge, United Kingdom) 1:300 dilution]. For each core, the percent positivity was quantified by the pathologist and Definiens Tissue Studio. Correlations between pathologist and computational scores were evaluated with Spearman correlation (for categorical positivity: 0, >0–<1, 1–10, >10–50, and >50%) and sensitivity/specificity (for binary positivity defined with 1 and 10% cut-offs), using the pathologist scores as the gold standard. Expression homogeneity was examined with intra-class correlation (ICC). Analyses were stratified by core [normal terminal duct-lobular units (TDLUs), benign lesions] and tissue type (epithelium, stroma).

Results

Spearman correlation between pathologist and Definiens ranged between 0.40–0.64 for stroma and 0.66–0.68 for epithelium in normal TDLUs cores and between 0.24–0.60 for stroma and 0.61–0.64 for epithelium in benign lesions. For stroma, sensitivity and specificity ranged between 0.92–0.95 and 0.24–0.60, respectively, with 1% cut-off and between 0.43–0.88 and 0.73–0.85, respectively, with 10% cut-off. For epithelium, 10% cut-off resulted in better estimates for both sensitivity and specificity. ICC between the cores was strongest for CD44 for both stroma and epithelium in normal TDLUs cores and benign lesions (range 0.74–0.80). ICC for CD24 and ALDH1A ranged between 0.42–0.63 and 0.44–0.55, respectively.

Conclusion

Our findings show that computational assessments for CD44, CD24, and ALDH1A1 exhibit variable correlations with manual assessment. These findings support the use of computational platforms for IHC evaluation of stem cell markers in large-scale epidemiologic studies. Pilot studies maybe also needed to determine appropriate cut-offs for defining staining positivity.
Recent changes in the mutational dynamics of the SARS-CoV-2 main protease substantiate the danger of emerging resistance to antiviral drugs
Authors: Parigger Lena , Krassnigg Andreas , Schopper Tobias , Singh Amit , Tappler Katharina , Köchl Katharina , Hetmann Michael , Gruber Karl , Steinkellner Georg , Gruber Christian C.
Published: December 2022

Introduction

The current coronavirus pandemic is being combated worldwide by nontherapeutic measures and massive vaccination programs. Nevertheless, therapeutic options such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main-protease (Mpro) inhibitors are essential due to the ongoing evolution toward escape from natural or induced immunity. While antiviral strategies are vulnerable to the effects of viral mutation, the relatively conserved Mpro makes an attractive drug target: Nirmatrelvir, an antiviral targeting its active site, has been authorized for conditional or emergency use in several countries since December 2021, and a number of other inhibitors are under clinical evaluation. We analyzed recent SARS-CoV-2 genomic data, since early detection of potential resistances supports a timely counteraction in drug development and deployment, and discovered accelerated mutational dynamics of Mpro since early December 2021.

Methods

We performed a comparative analysis of 10.5 million SARS-CoV-2 genome sequences available by June 2022 at GISAID to the NCBI reference genome sequence NC_045512.2. Amino-acid exchanges within high-quality regions in 69,878 unique Mpro sequences were identified and time- and in-depth sequence analyses including a structural representation of mutational dynamics were performed using in-house software.

Results

The analysis showed a significant recent event of mutational dynamics in Mpro. We report a remarkable increase in mutational variability in an eight-residue long consecutive region (R188-G195) near the active site since December 2021.

Discussion

The increased mutational variability in close proximity to an antiviral-drug binding site as described herein may suggest the onset of the development of antiviral resistance. This emerging diversity urgently needs to be further monitored and considered in ongoing drug development and lead optimization.