bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Status of Intracranial Pressure Monitoring in Patients with Severe Traumatic Brain Injury in Korea : A Post Hoc Analysis of Korea Neurotrauma Databank Project with a Nationwide Survey
Authors: Lee Youngheon , Lee Jung Hwan , Choi Hyuk Jin , Kim Byung Chul , Yu Seunghan , Ha Mahnjeong ,   the KNTDB Investigators
Published: April 2023

Objective : This study aimed to investigate the current status of intracranial pressure (ICP) monitoring in patients with severe traumatic brain injury (sTBI) in Korea and the association between ICP monitoring and prognosis. In addition, a survey was administered to Korean neurosurgeons to investigate the perception of ICP monitoring in patients with sTBI.Methods : This study used data from the second Korea Neurotrauma Databank. Among the enrolled patients with sTBI, the following available clinical data were analyzed in 912 patients : Glasgow coma scale score on admission, ICP monitoring, mortality, and extended Glasgow outcome scale score at 6 months. In addition, we administered a survey, entitled “current status and perception of ICP monitoring in Korean patients with sTBI” to 399 neurosurgeons who were interested in traumatic brain injury.Results : Among the 912 patients, 79 patients (8.7%) underwent ICP monitoring. The mortality and favorable outcome were compared between the groups with and without ICP monitoring, and no statistically significant results were found. Regarding the survey, there were 61 respondents. Among them, 70.4% of neurosurgeons responded negatively to performing ICP monitoring after craniectomy/craniotomy, while 96.7% of neurosurgeons responded negatively to performing ICP monitoring when craniectomy/ craniotomy was not conducted. The reasons why ICP monitoring was not performed were investigated, and most respondents answered that there were no actual guidelines or experiences with post-operative ICP monitoring for craniectomy/craniotomy. However, in cases wherein craniectomy/craniotomy was not performed, most respondents answered that ICP monitoring was not helpful, as other signs were comparatively more important.Conclusion : The proportion of performing ICP monitoring in patients with sTBI was low in Korea. The outcome and mortality were compared between the patient groups with and without ICP monitoring, and no statistically significant differences were noted in prognosis between these groups. Further, the survey showed that ICP monitoring in patients with sTBI was somewhat negatively recognized in Korea.
Nerves, Cough, and Idiopathic Pulmonary Fibrosis
Authors: Harrison Nicholas Kim , Pynn Michael C.
Published: April 2023

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It has a poor prognosis with a median survival of approximately 3 years, and whilst new therapies are finally beginning to offer hope of improved survival, most patients will require palliation of symptoms as their disease progresses. Whilst all patients with IPF complain of breathlessness, up to 80% develop a distressing cough, which is detrimental to their quality of life and difficult to treat. This article examines the possible causes of cough in the wider context of current theories of the pathogenesis of IPF and its associated comorbidities, which may also cause or exacerbate cough. We examine the evidence for increased cough sensitivity in patients with IPF and neuroplasticity in animal models of lung pathology. Finally, we discuss new therapies that are becoming available to treat cough in IPF and their possible mechanisms of action, and which highlight the need for further, appropriately powered studies that include objective measures of cough as an outcome.
The Evaluation and Management of Interstitial Cystitis/Bladder Pain Syndrome
Authors: Kraemer Samantha , Watson Brett , Peters Kenneth M
Published: April 2023

Interstitial cystitis or bladder pain syndrome is a frustrating symptom complex for both the patient and the clinician. Classic Hunner’s lesion interstitial cystitis is clearly a bladder disease and treating the bladder improves symptoms. Non-Hunner’s lesion interstitial cystitis or bladder pain syndrome likely has multiple aetiologies and in many cases the bladder is an innocent bystander in a bigger pelvic process. For many years, non-Hunner’s lesion interstitial cystitis has been treated with bladder-directed therapies, with poor overall outcomes. This literature review article will review the diagnosis and management of interstitial cystitis and encourage the reader to look beyond the bladder to achieve symptom relief.
A Systematic Review of Scrotal Squamous Cell Carcinoma
Authors: Sarkar Debashis
Published: April 2023

The epidemiology of scrotal cancer has changed over time away from occupational exposure to soot. The current incidence of scrotal malignancy is approximately 1 per 1 million males per year. This review summarises the current literature on the management of scrotal squamous cell carcinoma (SCC), including pathogenesis, available diagnostic tools, current treatment, and overall management strategies.

The rarity of SSC cases makes it difficult to recruit patients for studies of this disease. To date, very few studies have been performed, and those that have been completed were limited by a small sample size. This review analyses all available evidence, which varies from retrospective case series to prospective multicentre trials.

Psoralen ultraviolet light A treatment and human papillomavirus infection are significant risk factors for this cancer. Scrotal SCC had lower survival rates compared with other histological subtypes and the 5-year relative survival rate was 77%. Many studies also showed a positive margin, even after wide excision of the lesion. Excision of the primary lesion and a risk-stratified approach for staging and treatment of regional lymph nodes is the mainstay of current management strategies. For patients with clinically negative lymph nodes, sentinel lymph node biopsy and PET scans for patients with suspected pelvic node involvement has improved the diagnostic yield. The new neoadjuvant therapy (both chemotherapy and radiotherapy) has helped to downstage the disease for complete resection.

The prognosis of scrotal SCC is determined by margin-free excision, depth of infiltration, and its histologic grade. Future trials focussing on the conjunction of SCC with penile cancer, as well as the creation of a multinational network for ‘virtual’ online multidisciplinary meetings, will help to improve the overall survival for scrotal SCC patients.
Pengembangan Taman TOGA Untuk Peningkatan Kesehatan Warga Panti Asuhan Yafikhi Semarang
Authors: Susanti R. , Christijanti Wulan , Habibah Noor Aini , Mustikaningtyas Dewi , Sasi Fitri Arum , Galih Damar , Mumtaz Sasabila , Puspitasari Anisa Dewi Sri
Published: April 2023

Panti Asuhan Yafikhi memiliki lahan kosong yang berpotensi digunakan sebagai perkebunan. Tantangan dalam pengembangan pertanian hortikultura adalah keseimbangan penggunaan bahan organik dan anorganik. Tujuan dari kegiatan pengabdian ini adalah untuk memberdayakan warga panti asuhan Yafikhi dalam (1) merancang arsitektur landscape “Taman TOGA” sesuai dengan luas dan kondisi lahan, (2) mengumpulkan dan menanam toga sesuai dengan landscape yang telah dibuat, (3) Menerapkan bioteknologi dalam pemanfaatan limbah rumah tangga menjadi pupuk organik, (4) merawat dan mengelola kebun TOGA menggunakan pupuk organik, (5) memanfaatkan tanaman obat untuk menjaga kesehatan. Metode yang digunakan adalah workshop, praktik, dan pendampingan. Hasil pengabdian menunjukkan peningkatan pemahaman warga mitra (Panti Asuhan Yafikhi Semarang) tentang pentingnya tanaman obat untuk menjaga kesehatan, terampil merancang dan mewujudkan Taman TOGA, terampil mengelola sampah rumah tangga menjadi kompos padat dan pupuk organik cair, dan terampil menggunakan pupuk organik untuk memelihara taman TOGA.
Pemanfaatan Digital Marketing dalam Percepatan Rintisan Taman Agrowisata Di Desa Tamanrejo Kecamatan Limbangan Kabupaten Kendal
Authors: Meiriyanti Rita , Sijabat Rauly , Nastiti Prianka Ratri
Published: April 2023

Berdasarkan hasil survey dan wawancara yang dilakukan dengan pihak terkait diketahui bahwa permasalahan utama taman Agrowisata di Desa Tamanrejo adalah belum terbangunnya sistem jaringan pemasaran dan promosi produk kepariwisataan. Program Kemitraan Masyarakat ini bertujuan untuk mendorong percepatan rintisan taman Agrowisata di Desa Tamanrejo melalui pemanfaatan peran digital marketing. Dengan menggunakan model digital roadtrip melalui platform Instagram dan Facebook ditemukan bahwa metode tersebut mampu mempromosikan potensi wisata di Desa Tamanrejo, karena fitur utamanya yang mengunggulkan pembagian gambar dan video, sehingga pengguna Instagram dan Facebook seolah-olah merasa berada di kawasan taman Agrowisata. Penggunaan platform Youtube sebagai media untuk mengunggah, menonton, dan berbagi video profil taman Agrowisata. Kegiatan pelatihan mengenai pemanfaatan digital marketing dinilai tepat dilakukan kepada penduduk usia muda, sebagai proporsi terbesar pengguna aktif media sosial. Dengan pelatihan yang dilaksanakan, kelompok pemuda di Desa Tamanrejo dapat secara mandiri merancang konten di media sosial untuk tujuan promosi. Temuan penting dalam pengabdian masyarakat ini adalah guna mencapai percepatan rintisan taman Agrowisata, diperlukan sinergi yang menyeluruh dari semua lapisan Masyarakat. Caranya dengan mendorong pengguna aktif Instagram, Facebook, dan Youtube di Desa Tamanrejo untuk mengikuti “Instagram, Facebook, dan Youtube taman Agrowisata,” membagikan setiap momen yang dilakukan ketika bersinggungan dengan aktivitas wisata di taman Agrowisata.
Molecular mechanisms of drug resistance in breast cancer and potential strategies for overcoming resistance
Authors: Pradubyat Nalinee , Laoharuangchaiyot Jutatip
Published: April 2023

Breast cancer is the most common cause of death from cancer in the world, and drug resistance is one of the most significant barriers to successful therapy for the disease. It is critical to have a solid understanding of the molecular processes driving treatment resistance in breast cancer to design targeted therapies with the potential to overcome this resistance. These complex and multifaceted mechanisms include the activation of signaling pathways that promote cell survival and proliferation, the upregulation of drug efflux pumps, the emergence of cancer stem cells, and genetic and epigenetic changes. This literature review provides an overview of these mechanisms. It discusses potential strategies for overcoming drug resistance in breast cancer, including targeted therapies that specifically target the pathways and mechanisms involved in drug resistance. The review also highlights the need for further research to identify effective strategies for overcoming drug resistance and improving treatment outcomes in breast cancer patients.
PAOX1 expression in mixed-substrate continuous cultures of Komagataella phaffii (Pichia pastoris) is completely determined by methanol consumption regardless of the secondary carbon source
Authors: Singh Anamika , Narang Atul
Published: April 2023

The expression of recombinant proteins by the AOX1 promoter of Komagataella phaffii is typically induced by adding methanol to the cultivation medium. Since growth on methanol imposes a high oxygen demand, the medium is often supplemented with an additional secondary carbon source which serves to reduce the consumption of methanol, and hence, oxygen. Early research recommended the use of glycerol as the secondary carbon source, but more recent studies recommend the use of sorbitol because glycerol represses PAOX1 expression. To assess the validity of this recommendation, we measured the steady state concentrations of biomass, residual methanol, and LacZ expressed from PAOX1 over a wide range of dilution rates (0.02–0.20 h−1) in continuous cultures of the Mut+ strain fed with methanol + glycerol (repressing) and methanol + sorbitol (non-repressing). We find that under these conditions, the specific PAOX1 expression rate (measured as either specific LacZ productivity or specific AOX productivity) is completely determined by the specific methanol consumption rate regardless of the type (repressing/non-repressing) of the secondary carbon source. In both cultures, the specific PAOX1 expression rate is proportional to the specific methanol consumption rate, provided that the latter is below 0.15 g/(gdw-h); beyond this threshold consumption rate, the specific PAOX1 expression rate of both cultures saturates to the same value. Analysis of the data in the literature shows that the same phenomenon also occurs in continuous cultures of Escherichia coli fed with mixtures of lactose plus repressing/non-repressing carbon sources. The specific Plac expression rate is completely determined by the specific lactose consumption rate, regardless of the type of secondary carbon source, glycerol or glucose.
Modulation of T-cell function by myeloid-derived suppressor cells in hematological malignancies
Authors: Bhardwaj Vaishali , Ansell Stephen M.
Published: April 2023

Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes that negatively regulate the immune response to cancer and chronic infections. Abnormal myelopoiesis and pathological activation of myeloid cells generate this heterogeneous population of myeloid-derived suppressor cells. They are characterized by their distinct transcription, phenotypic, biochemical, and functional features. In the tumor microenvironment (TME), myeloid-derived suppressor cells represent an important class of immunosuppressive cells that correlate with tumor burden, stage, and a poor prognosis. Myeloid-derived suppressor cells exert a strong immunosuppressive effect on T-cells (and a broad range of other immune cells), by blocking lymphocyte homing, increasing production of reactive oxygen and nitrogen species, promoting secretion of various cytokines, chemokines, and immune regulatory molecules, stimulation of other immunosuppressive cells, depletion of various metabolites, and upregulation of immune checkpoint molecules. Additionally, the heterogeneity of myeloid-derived suppressor cells in cancer makes their identification challenging. Overall, they serve as a major obstacle for many cancer immunotherapies and targeting them could be a favorable strategy to improve the effectiveness of immunotherapeutic interventions. However, in hematological malignancies, particularly B-cell malignancies, the clinical outcomes of targeting these myeloid-derived suppressor cells is a field that is still to be explored. This review summarizes the complex biology of myeloid-derived suppressor cells with an emphasis on the immunosuppressive pathways used by myeloid-derived suppressor cells to modulate T-cell function in hematological malignancies. In addition, we describe the challenges, therapeutic strategies, and clinical relevance of targeting myeloid-derived suppressor cells in these diseases.
Dose-dependent effect of GFI1 expression in the reconstitution and the differentiation capacity of HSCs
Authors: Xie Xiaoqing , Patnana Pradeep Kumar , Frank Daria , Schütte Judith , Al-Matary Yahya , Künstner Axel , Busch Hauke , Ahmed Helal , Liu Longlong , Engel Daniel R. , Dührsen Ulrich , Rosenbauer Frank , Von Bubnoff Nikolas , Lenz Georg , Khandanpour Cyrus
Published: April 2023

GFI1 is a transcriptional repressor and plays a pivotal role in regulating the differentiation of hematopoietic stem cells (HSCs) towards myeloid and lymphoid cells. Serial transplantation of Gfi1 deficient HSCs repopulated whole hematopoietic system but in a competitive setting involving wild-type HSCs, they lose this ability. The underlying mechanisms to this end are poorly understood. To better understand this, we used different mouse strains that express either loss of both Gfi1 alleles (Gfi1-KO), with reduced expression of GFI1 (GFI1-KD) or wild-type Gfi1/GFI1 (Gfi1-/GFI1-WT; corresponding to the mouse and human alleles). We observed that loss of Gfi1 or reduced expression of GFI1 led to a two to four fold lower number of HSCs (defined as Lin−Sca1+c-Kit+CD150+CD48−) compared to GFI1-WT mice. To study the functional influence of different levels of GFI1 expression on HSCs function, HSCs from Gfi1-WT (expressing CD45.1 + surface antigens) and HSCs from GFI1-KD or -KO (expressing CD45.2 + surface antigens) mice were sorted and co-transplanted into lethally irradiated host mice. Every 4 weeks, CD45.1+ and CD45.2 + on different lineage mature cells were analyzed by flow cytometry. At least 16 weeks later, mice were sacrificed, and the percentage of HSCs and progenitors including GMPs, CMPs and MEPs in the total bone marrow cells was calculated as well as their CD45.1 and CD45.2 expression. In the case of co-transplantation of GFI1-KD with Gfi1-WT HSCs, the majority of HSCs (81% ± 6%) as well as the majority of mature cells (88% ± 10%) originated from CD45.2 + GFI1-KD HSCs. In the case of co-transplantation of Gfi1-KO HSCs with Gfi1-WT HSCs, the majority of HSCs originated from CD45.2+ and therefore from Gfi1-KO (61% ± 20%); however, only a small fraction of progenitors and mature cells originated from Gfi1-KO HSCs (<1%). We therefore in summary propose that GFI1 has a dose-dependent role in the self-renewal and differentiation of HSCs.
Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
Authors: James Christopher , Gomez Kayeromi , Desai Shalin , Patel Hiten D. , Rac Goran , Doshi Chirag P. , Dornbier Ryan , Bajic Petar , Halverson Thomas , Gupta Gopal N. , Quek Marcus L. , Gorbonos Alex , Flanigan Robert , Wolfe Alan J.
Published: April 2023

Introduction

Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC.

Methods

Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated.

Results

Across the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort.

Conclusion

IVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.
Study on the process of cardiomyocyte apoptosis after pulsed field ablation
Authors: Fan Shaobo , Jia Fenglin , Cui Yingjian , Wu Dongyan , He Le , Zhang Fan , Xue Zhixiao , Xu Xinyu , Lu Fengmin , Ma Wei , Su Siying , Chen Yanpeng , Liu Zhenxu
Published: April 2023

Background

The development of pulsed field ablation (PFA) as a new technique for pulmonary vein isolation (PVI) has been advancing rapidly in recent years. My team's previous work has shown the safety and long-term efficacy of bipolar asymmetric pulses in animal experiments. However, in ongoing clinical trials, we have observed that atrial fibrillation (AF) recurs in some patients after surgery, but the rhythm returns to normal without surgical intervention after seven days, and there is no recurrence in the follow-up.Based on this observation, we have proposed the hypothesis that myocardial cell apoptosis may play a role in AF recurrence after PFA. Our team has designed animal experiments to verify this hypothesis and further investigate the process of PFA-induced cardiomyocyte apoptosis.

Methods

Pulse field ablation was performed on 15 dogs and the animals were dissected at various time points after the operation (immediately, 3 days, 7 days, 30 days, and 150 days). To obtain ablation voltage maps, electroanatomic mapping was performed before and after ablation and before dissection. The ablation area was also subjected to HE and TUNEL staining to analyze apoptosis and pathological results.

Results

The edge area of the ablation in the pulmonary vein (PV) demonstrated continuous dynamic changes from 0 to 2 h after the operation and a slight expansion of the ablation range was observed in the long-term follow-up. Myocardial intima hyperplasia was observed from 0 to 7 days. Local apoptosis was detected from 0 to 2 h and massive, concentrated apoptosis was observed at 3 days. No recurrence of apoptosis was seen at 7 days, 30 days, and 150 days.

Conclusions

The results of this study showed that after pulse field ablation (PFA), the central ablation area of the canine heart experienced immediate cardiomyocyte death. Meanwhile, cardiomyocytes in the edge ablation area underwent apoptosis, which began from 0 to 2 h post-operation and ended between 3 and 7 days. This process occurred simultaneously with intimal thickening.In the long-term follow-up group, there was no recovery of isolation and no recurrence of cardiomyocyte apoptosis, and no change was observed in the endomyocardial intima.
Crustal thickness of the Jiaodong Peninsula in the Mesozoic: Implications for the destruction of the North China Craton
Authors: Dong Leilei , Bai Xin , Song Mingchun , Wang Runsheng
Published: April 2023

The North China Craton underwent extensive and widespread crustal reworking (or decratonization) during the Mesozoic. However, how the decratonization operated is not well understood. Zircon compositions are widely used by the scientific community to reconstruct crustal thicknesses. In this study, we sampled 13 magmatic rocks in the Jiaodong Peninsula and used zircon Eu/Eu* to constrain the crustal thickness of the Jiaodong area and reveal decratonization processes in the Mesozoic time. The reconstructed crustal thickness using zircon Eu/Eu* is approximately 70 km in the Jurassic, and this value is 89 km at around 130 Ma, after which the crustal thickness drops to 30–40 km at ca. 110 Ma. These results are generally compatible with or slightly higher than the calculation results using a whole-rock La/Yb proxy for the Jurassic and ∼130 Ma rocks. Crustal thickness estimated using a whole-rock La/Yb proxy for the ∼110 Ma rocks is thicker than 70 km, which is not consistent with the geological facts and the result given by zircon proxy. The whole-rock proxy failed in estimating crustal thickness because of amphibole fractionation for the ∼110 Ma rocks. The crustal thickening from Jurassic to ∼130 Ma was probably related to the westward subduction of the Paleo-Pacific slab. The thinning of the crust from 130 to 110 Ma is not a rapid process but occurs more slowly than expected, which might be explained by the chemical erosion process rather than a mechanical delamination model. The chemical erosion was most likely induced by a rollback of the subducting slab and an upwelling of the asthenosphere.
Dyslipidemia and serum cystatin C levels as biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus
Authors: Dejenie Tadesse Asmamaw , Abebe Endeshaw Chekol , Mengstie Misganaw Asmamaw , Seid Mohammed Abdu , Gebeyehu Natnael Atnafu , Adella Getachew Asmare , Kassie Gizchew Ambaw , Gebrekidan Amanuel Yosef , Gesese Molalegn Mesele , Tegegne Kirubel Dagnaw , Anley Denekew Tenaw , Feleke Sefineh Fenta , Zemene Melkamu Aderajew , Dessie Anteneh Mengist , Moges Natnael , Kebede Yenealem Solomon , Bantie Berihun , Adugna Dagnew Getnet
Published: April 2023

Background

Diabetic nephropathy is a leading cause of end-stage renal disease. The diagnostic markers of nephropathy, including the presence of albuminuria and/or a reduced estimated glomerular filtration rate, are not clinically ideal, and most of them are raised after a significant reduction in renal function. Therefore, it is crucial to seek more sensitive and non-invasive biomarkers for the diagnosis of diabetic nephropathy.

Objective of the study

This study aimed to investigate the serum cystatin C levels and dyslipidemia for the detection of diabetic nephropathy in patients with type 2 diabetes mellitus.

Methodology

A hospital-based comparative cross-sectional study was conducted from December 2021 to August 2022 in Tikur, Anbessa specialized teaching hospital with a sample size of 140 patients with type2 diabetes mellitus. Socio-demographic data was collected using a structured questionnaire, and 5 mL of blood was collected from each participant following overnight fasting for biochemical analyses.

Results

In type 2 diabetes patients with nephropathy, we found significant lipoprotein abnormalities and an increase in serum cystatin C (P < 0.001) compared to those without nephropathy. Serum cystatin C, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, low density lipoprotein, very low-density lipoprotein, high density lipoprotein, and duration of diabetes were identified as being significantly associated with diabetic nephropathy (P < 0.05) in multivariable logistic regression analysis. The mean values of total cholesterol levels, triglyceride levels, and high-density lipoprotein cholesterol levels were also found to be significantly higher (P < 0.05) in females as compared to male type-2 diabetic patients. The fasting blood glucose levels and lipid profiles of the participants were found to be significantly associated with serum cystatin C levels.

Conclusion

The present study found significant serum cystatin C and lipoprotein abnormalities in T2DM patients with diabetic nephropathy when compared with those without diabetic nephropathy, and these lipoprotein abnormalities were significantly associated with serum cystatin C levels.
Association of miR-196a2 and miR-27a polymorphisms with gestational diabetes mellitus susceptibility in a Chinese population
Authors: Zeng Qiaoli , Zou Dehua , Liu Na , Wei Yue , Yang Jing , Wu Weibiao , Han Fengqiong , He Rongrong , Guo Runmin
Published: April 2023

Introduction

MiR-196a2 and miR-27a play a key role in the regulation of the insulin signaling pathway. Previous studies have indicated that miR-27a rs895819 and miR-196a2 rs11614913 have a strong association with type 2 diabetes (T2DM), but very few studies have investigated their role in gestational diabetes mellitus (GDM).

Methods

A total of 500 GDM patients and 502 control subjects were enrolled in this study. Using the SNPscan™ genotyping assay, rs11614913 and rs895819 were genotyped. In the data treatment process, the independent sample t test, logistic regression and chi-square test were used to evaluate the differences in genotype, allele, and haplotype distributions and their associations with GDM risk. One-way ANOVA was conducted to determine the differences in genotype and blood glucose level.

Results

There were obvious differences in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP) and parity between GDM and healthy subjects (P < 0.05). After adjusting for the above factors, the miR-27a rs895819 C allele was still associated with an increased risk of GDM (C vs. T: OR=1.245; 95% CI: 1.011-1.533; P = 0.039) and the TT-CC genotype of rs11614913-rs895819 was related to an increased GDM risk (OR=3.989; 95% CI: 1.309-12.16; P = 0.015). In addition, the haplotype T-C had a positive interaction with GDM (OR=1.376; 95% CI: 1.075-1.790; P=0.018), especially in the 18.5 ≤ pre-BMI < 24 group (OR=1.403; 95% CI: 1.026-1.921; P=0.034). Moreover, the blood glucose level of the rs895819 CC genotype was significantly higher than that of the TT and TC genotypes (P < 0.05). The TT-CC genotype of rs11614913-rs895819 showed that the blood glucose level was significantly higher than that of the other genotypes.

Discussion

Our findings suggest that miR-27a rs895819 is associated with increased GDM susceptibility and higher blood glucose levels.
Spatial heterogeneity and Immune infiltration of cellular lysosomal pathways reveals a new blueprint for tumor heterogeneity in esophageal cancer
Authors: Wei Jinxing , Wu XiaoMing , Wang Shuohao , Liu Siqing , Gao Xia
Published: April 2023

Background

Esophageal squamous cell carcinoma (ESCC) is a common Malignant tumor of digestive tract which have a potential association with lysosomal pathway. The purpose of this study was to explore the correlation between lysosome pathway and immune infiltration of ESCC.

Methods

The cell type annotation of ESCC patients and the distribution of their gene markers were analyzed by single cell data. They were also grouped according to the expression of lysosomal pathways. Gene set variation analysis (GSVA) enriched pathway scoring, Cellchat cell communication was performed to demonstrate the tumour-associated pathway scores and interactions of different cell populations. Relevant differential genes were screened, prognostic risk markers were constructed and direct associations of lysosomal pathway-related gene risk scores with immune infiltration and tumour treatment drug sensitivity were assessed by algorithms. In cellular experiments, qPCR and flow cytometry were used to assess the role of the lysosomal pathway gene-MT1X on tumour cell development.

Results

ESCC single cell data were annotated into 7 Cluster clusters by t-sne downscaling analysis. Cellchat analysis revealed that the “MIF” cellular communication network is the main communication mode of the lysosomal pathway in ESCC cells. The lysosomal pathway genetic risk model was found to be significantly different from ESCC prognosis in both the training and validation groups. The lysosome pathway gene risk model was associated with treatment resistance in ESCC patients using oncopredict R package. The correlation between the expression of lysosomal-DEG and tumour immune infiltration and immune cell types by the MCPcounter method. Cellular assays showed that the lysosomal pathway gene MT1X was less expressed in oesophageal cancer cells than in normal oesophageal epithelial cells. Knockdown of MT1X significantly promoted the growth rate of oesophageal cancer cells.

Conclusion

Based on the single cell sequencing technology and transcriptomic analysis, we confirmed that there is a close association between the lysosomal pathway and the immune infiltration and treatment sensitivity of ESCC, which may be a potential target for a new direction of ESCC therapy.
Missed meal boluses and poorer glycemic control impact on neurocognitive function may be associated with white matter integrity in adolescents with type 1 diabetes
Authors: Litmanovitch Edna , Geva Ronny , Leshem Avital , Lezinger Mirit , Heyman Eli , Gidron Maor , Yarmolovsky Jessica , Sasson Efrat , Tal Sigal , Rachmiel Marianna
Published: April 2023

Background

The notion that pediatric type 1 diabetes impacts brain function and structure early in life is of great concern. Neurological manifestations, including neurocognitive and behavioral symptoms, may be present from childhood, initially mild and undetectable in daily life. Despite intensive management and technological therapeutic interventions, most pediatric patients do not achieve glycemic control targets for HbA1c. One of the most common causes of such poor control and frequent transient hyperglycemic episodes may be lifestyle factors, including missed meal boluses.

Objective

The aim of this study was to assess the association between specific neurocognitive accomplishments—learning and memory, inhibition ability learning, and verbal and semantic memory—during meals with and without bolusing, correlated to diffusion tensor imaging measurements of major related tracts, and glycemic control in adolescents with type 1 diabetes compared with their healthy siblings of similar age.

Study design and methods

This is a case–control study of 12- to 18-year-old patients with type 1 diabetes (N = 17, 8 male patients, diabetes duration of 6.53 ± 4.1 years) and their healthy siblings (N = 13). All were hospitalized for 30 h for continuous glucose monitoring and repeated neurocognitive tests as a function of a missed or appropriate pre-meal bolus. This situation was mimicked by controlled, patient blinded manipulation of lunch pre-meal bolus administration to enable capillary glucose level of <180 mg/dl and to >240 mg/d 2 hours after similar meals, at a similar time. The diabetes team randomly and blindly manipulated post-lunch glucose levels by subcutaneous injection of either rapid-acting insulin or 0.9% NaCl solution before lunch. A specific neurocognitive test battery was performed twice, after each manipulation, and its results were compared, along with additional neurocognitive tasks administered during hospitalization without insulin manipulation. Participants underwent brain imaging, including diffusion tensor imaging and tractography.

Results

A significant association was demonstrated between glycemic control and performance in the domains of executive functions, inhibition ability, learning and verbal memory, and semantic memory. Inhibition ability was specifically related to food management. Poorer glycemic control (>8.3%) was associated with a slower reaction time.

Conclusion

These findings highlight the potential impairment of brain networks responsible for learning, memory, and controlled reactivity to food in adolescents with type 1 diabetes whose glycemic control is poor.
Note on the potential to increase the accuracy of source term calculations for spent nuclear fuel
Authors: Seidl Marcus , Schillebeeckx Peter , Rochman Dimitri
Published: April 2023

The accuracy of source term predictions is an important factor which determines the efficiency of interim and final storage of spent nuclear fuel. To minimize the required number of storage containers and to minimize the volume and mass of facilities while maintaining safety margins requires accurate codes to predict the decay heat and the gamma and neutron sources with minimum bias for time points ranging from months to thousands of years. While the relevant nuclear data for the purpose of criticality safety received high attention in the last decades and have been extensively verified with dedicated tests, nuclear data relevant for spent nuclear fuel had smaller priority. Mostly results from a radiochemical analysis of samples taken from commercially irradiated fuel have been used for validation purposes. The comparatively sparse data available from tests which exclusively focus on nuclide vector validation under research conditions means that many factors enter the uncertainty estimate of the measurement-theory comparisons and limits the ability to validate codes to a high accuracy. Firstly, the current status of validation efforts is reviewed. Secondly, fields of improvement are explored. Thirdly, the character of uncertainty distributions in measurement-theory comparisons (C/E) of nuclide vectors is analyzed. Currently there are indications that the C/E data is thick tailed which limits improvement of code validation efforts.
How chronic anthropogenic noise can affect wildlife communities
Authors: Kok Annebelle C. M. , Berkhout Boris W. , Carlson Nora V. , Evans Neil P. , Khan Nicola , Potvin Dominique A. , Radford Andrew N. , Sebire Marion , Shafiei Sabet Saeed , Shannon Graeme , Wascher Claudia A. F.
Published: April 2023

Anthropogenic noise is a major pollutant in terrestrial and aquatic ecosystems. Since the industrial revolution, human activities have become increasingly noisy, leading to both acute and chronic disturbance of a wide variety of animals. Chronic noise exposure can affect animals over their lifespan, leading to changes in species interactions and likely altering communities. However, the community-level impacts of chronic noise are not well-understood, which impairs our ability for effective mitigation. In this review, we address the effects of chronic noise exposure on communities and explore possible mechanisms underlying these effects. The limited studies on this topic suggest that noise can affect communities by changing the behavior and/or physiology of species in a community, which results in direct or knock-on consequences for other species in the ecosystem. Major knowledge gaps remain due to the logistically complex and financially expensive nature of the long-term studies needed to address these questions. By identifying these gaps and suggesting approaches to answer them, we provide a road map toward mitigating the effects of a noisy world.
Disease threats to tigers and their prey
Authors: Gilbert Martin , Dvornicky-Raymond Zachary , Bodgener Jessica
Published: April 2023

The contraction of the global tiger population over the last 100 years into small, often isolated subpopulations has made them increasingly vulnerable to the impact of disease. Despite this, the health of wild tigers continues to be insufficiently funded and explored. For example, canine distemper virus (CDV), has been associated with localized declines and increased risk of extinction, and yet has received little research attention in most tiger range countries. The emergence of new pathogenic threats has posed fresh challenges, including African swine fever virus (ASFV), which has the potential to devastate wild boar populations, and severe acute respiratory syndrome coronavirus (SARS-CoV2) with implications for tiger conservation that remain unknown. The objective of this review is to synthesize current research on the health of tigers and their prey that impacts the conservation of tigers in the wild. Published sources are interpreted based on three mechanisms through which disease can affect the viability of tiger populations: (1) by reducing the survival of adult tigers, (2) by reducing breeding productivity, and (3) by reducing the carrying capacity of tiger habitat through decreased prey abundance. Examples of CDV, SARS-CoV2, carnivore protoparvovirus 1 and ASFV are used to illustrate these processes and inform discussion of research and mitigation priorities.
Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs
Authors: Brady Rachel V. , Thamm Douglas H.
Published: April 2023

Macrophages are ancient, phagocytic immune cells thought to have their origins 500 million years ago in metazoan phylogeny. The understanding of macrophages has evolved to encompass their foundational roles in development, homeostasis, tissue repair, inflammation, and immunity. Notably, macrophages display high plasticity in response to environmental cues, capable of a strikingly wide variety of dynamic gene signatures and phenotypes. Macrophages are also involved in many pathological states including neural disease, asthma, liver disease, heart disease, cancer, and others. In cancer, most tumor-associated immune cells are macrophages, coined tumor-associated macrophages (TAMs). While some TAMs can display anti-tumor properties such as phagocytizing tumor cells and orchestrating an immune response, most macrophages in the tumor microenvironment are immunosuppressive and pro-tumorigenic. Macrophages have been implicated in all stages of cancer. Therefore, interest in manipulating macrophages as a therapeutic strategy against cancer developed as early as the 1970s. Companion dogs are a strong comparative immuno-oncology model for people due to documented similarities in the immune system and spontaneous cancers between the species. Data from clinical trials in humans and dogs can be leveraged to further scientific advancements that benefit both species. This review aims to provide a summary of the current state of knowledge on macrophages in general, and an in-depth review of macrophages as a therapeutic strategy against cancer in humans and companion dogs.
Differential analysis of fish meal substitution with two soybean meals on juvenile pearl gentian grouper
Authors: Pang Aobo , Xin Yu , Xie Ruitao , Wang Zhuoduo , Zhang Wei , Tan Beiping
Published: April 2023

Fermented soybean meal and soybean protein concentrate are products of soybean that have been processed physically or biologically, and their use as an alternative to fish meal results in a significant reduction in the effects of anti-nutritional factors (ANFs) in soybean on aquatic species. Replacing fish meal with soybean protein concentrate and fermented soybean meal can meet the high protein requirements of carnivorous fish while effectively reducing aquaculture costs; however, excessive substitution can also cause economic losses. In this study, we used transcriptome sequencing to investigate the impacts of fermented soybean meal and soybean protein concentrate on the growth and physiology of pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) juveniles and to examine the mechanisms by which fermented soybean meal and soybean protein concentrate impair the intestinal condition of fish. Originally weighed 12.55 ± 0.06 g, the selected pearl gentian groupers were categorised into three treatment groups: one group was fed fish meal-based diets (FM, control group), one group was fed fish meal- and soybean protein concentrate-based diets (SPC40) and one group was fed fish meal- and fermented soybean meal-based diets (FSBM40), with the same crude protein and crude fat content in all three diets. The experiment was conducted for 10 weeks. The growth results showed that both the fermented soybean meal and soybean protein concentrate diets significantly inhibited the growth of the fish. Based on the results of enzyme activity, substance content and gene expression levels associated with intestinal damage and intestinal inflammation, it is highly likely that the fermented soybean meal and soybean protein concentrate diets affected the intestinal health of the fish and triggered intestinal inflammation. This study provides a theoretical basis to further explore the mechanism of soybean-initiated intestinal problems in fish.
Efficacy and safety of Tuina (Chinese Therapeutic Massage) for knee osteoarthritis: A randomized, controlled, and crossover design clinical trial
Authors: Liu Kaoqiang , Zhan Yunfan , Zhang Yujie , Zhao Ye , Chai Yongli , Lv Hua , Yuan Weian
Published: April 2023

Background

Knee osteoarthritis (KOA) is a highly prevalent joint disease among the middle-aged and elderly population that can lead to pain, functional impairment, decreased quality of life, and a large number of medical expenses. Physical therapy is one of the main treatment methods for KOA. In China, Tuina has been widely used in the treatment of KOA, but up to now, there is no high-quality medical evidence to support its effectiveness and safety. The purpose of this study was to objectively evaluate the efficacy and safety of Tuina in the treatment of KOA.

Methods

A crossover design clinical trial was performed on 96 patients. The test group and the control group in the trial were allocated randomly in a ratio of 1:1. The test group received Tuina treatment for 4 weeks first and then received health education intervention for another 4 weeks. The control group received health education intervention for 4 weeks first and then received Tuina treatment for another 4 weeks. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score was chosen as the primary outcome. The WOMAC pain score, WOMAC stiffness, WOMAC daily activity score, and visual analog scale (VAS) score were the secondary outcomes. Adverse events during the intervention were collected in both groups.

Results

Compared with the baseline, the WOMAC total score, WOMAC pain score, WOMAC stiffness, WOMAC daily activity, and VAS score of patients in both groups were improved significantly at weeks 4 and 8 (p < 0.001). All patients who received Tuina treatment were significantly superior to those who received health education intervention in the WOMAC total score (194.96, 95% CI = 164.94–224.97, P < 0.001), WOMAC pain score (45.96, 95% CI = 35.82–56.09, P < 0.001), WOMAC stiffness (31.42, 95% CI = 26.37–36.46, P < 0.001), WOMAC daily activity (117.58, 95% CI = 97.56–137.61, P < 0.001), and VAS score (1.07, 95% CI = 0.83–1.32, P < 0.001). Both groups had no serious adverse events during the treatment.

Conclusion

This trial demonstrated that Tuina can reduce joint pain in patients with KOA and improve the physical functions of the knee joint effectively and safely.

Clinical trial registration

This trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR-TTRCC-13003157). http://www.chictr.org.cn/showproj.aspx?proj=6402.
Effects of phenyl acids on different degradation phases during thermophilic anaerobic digestion
Authors: Prem Eva Maria , Schwarzenberger Alessa , Markt Rudolf , Wagner Andreas Otto
Published: April 2023

Aromatic compounds like phenyl acids (PA) can accumulate during anaerobic digestion (AD) of organic wastes due to an increased entry of lignocellulose, secondary plant metabolites or proteins, and thermodynamic challenges in degrading the benzene ring. The effects of aromatic compounds can be various – from being highly toxic to be stimulating for methanogenesis – depending on many parameters like inoculum or molecular characteristics of the aromatic compound. To contribute to a better understanding of the consequences of PA exposure during AD, the aim was to evaluate the effects of 10 mM PA on microbial communities degrading different, degradation phase–specific substrates in thermophilic batch reactors within 28  days: Microcrystalline cellulose (MCC, promoting hydrolytic to methanogenic microorganisms), butyrate or propionate (promoting syntrophic volatile fatty acid (VFA) oxidisers to methanogens), or acetate (promoting syntrophic acetate oxidisers to methanogens). Methane production, VFA concentrations and pH were evaluated, and microbial communities and extracellular polymeric substances (EPS) were assessed. The toxicity of PA depended on the type of substrate which in turn determined the (i) microbial diversity and composition and (ii) EPS quantity and quality. Compared with the respective controls, methane production in MCC reactors was less impaired by PA than in butyrate, propionate and acetate reactors which showed reductions in methane production of up to 93%. In contrast to the controls, acetate concentrations were high in all PA reactors at the end of incubation thus acetate was a bottle-neck intermediate in those reactors. Considerable differences in EPS quantity and quality could be found among substrates but not among PA variants of each substrate. Methanosarcina spp. was the dominant methanogen in VFA reactors without PA exposure and was inhibited when PA were present. VFA oxidisers and Methanothermobacter spp. were abundant in VFA assays with PA exposure as well as in all MCC reactors. As MCC assays showed higher methane yields, a higher microbial diversity and a higher EPS quantity and quality than VFA reactors when exposed to PA, we conclude that EPS in MCC reactors might have been beneficial for absorbing/neutralising phenyl acids and keeping (more susceptible) microorganisms shielded in granules or biofilms.