bluuebunny/crossref_metadata_2025 huggingface dataset:
Hubungan Program Pemberian Makanan Tambahan dengan Ibu Hamil Kekurangan Energi Kronis (KEK): Literature Review
Authors: Erna Erna , Misnaniarti Misnaniarti , Idris Haerawati
Published: July 2023

Kurang Energi Kronis (KEK) merupakan masalah gizi pada ibu hamil yang hingga saat ini masih menjadi permasalah gizi di dunia. Upaya yang dilakukan dalam perbaikan gizi ibu hamil KEK adalah dengan pemberian makanan tambahan. Tujuan: untuk mengetahui hubungan program pemberian makanan tambahan dengan ibu hamil kekurangan energi kronik (KEK). Metode: penelitian ini menggunakan literature review dengan cara mengumpulkan artikel yang sesuai topik dan tujuan penulisan yang didapat dari berbagai databased jurnal. Telaah dilakukan dengan menganalisis artikel ilmiah yang didapat dari database elektronik google scholar dan scopus dengan kriteria inklusi, tahun 2013-2023, bahasa indonesia dan bahasa Inggris. Teknik analisis artikel penelitian yaitu dengan format tabel yang berisi penulis, judul, tahun, metode (desain, sampel dan analisis), dan hasil. Hasil: hasil penelitian didapatkan 10 artikel dengan menggunakan perumusan PICO. Berdasarkan 10 artikel penelitian yang diperoleh, menunjukkan bahwa pemberian program pemberian makanan tambahan (PMT) pada ibu hami kekurangan energi kronik (KEK) berpengaruh pada kenaikan asupan energi total, status gizi, berat badan, penambahan lingkar lengan atas (LILA), penurunan kadar malondialdehyde, kekurangan vitamin A dan bayi dengan ibu KEK yang mengonsumsi PMT lahir dengan normal, tidak mengalami BBLR (Bayi Berat Lahir Rendah). Studi literature review ini diharapkan bisa menjadi referensi khususnya dalam bidang kesehatan masyarakat.
Pemahaman Siswa Tentang Penerapan Protokol Kesehatan Selama Pembelajaran Tatap Muka
Authors: Sari Armenia Diah , Rahmadewi Triani
Published: July 2023

Coronavirus Disease 2019 (COVID 19) adalah penyakit menular yang disebabkan oleh Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2). Kelompok usia yang berisiko terjangkit COVID-19 salah satunya anak usia sekolah dan remaja. Pembelajaran tatap muka di sekolah harus dilaksanakan dengan hati-hati agar sekolah tidak menjadi cluster baru penyebaran COVID-19. Pengetahuan dan perilaku siswa penting dalam penerapan protokol kesehatan selama pembelajaran tatap muka. Tujuan dalam penelitian ini untuk menggambarkan pengetahuan dan perilaku siswa tentang penerapan protokol kesehatan selama pembelajaran tatap muka di SD Muhammadiyah Mutihan Wates Yogayakarta. Penelitian ini merupakan penelitian deskriptif analitik dengan cross-sectional. Sampel dalam penelitian ini berjumlah 85 siswa dengan teknik pengambilan sampel menggunakan teknik purposive sampling dengan menggunakan kuesioner pengetahuan dan perilaku. Pengumpulan data menggunakan kuesioner. Hasil penelitian didapatkan yaitu pengetahuan siswa dalam penerapan protokol kesehatan dengan kategori baik sebanyak 58,8% dan kurang sebanyak 42,2%, sedangkan untuk perilaku siswa dengan kategori baik sebanyak 76,5% dan kurang 23,5%. Di harapkan sekolah tetap mempertahankan pengetahuan siswa tentang protokol kesehatan dan selalu memberikan edukasi kepada siswa dalam penerapan protokol kesehatan disekolah.
Overview of Advanced Numerical Methods Classified by Operation Dimensions
Authors: Gao Xiao-Wei , Jiang Wei-Wu , Xu Xiang-Bo , Liu Hua-Yu , Yang Kai , Lv Jun , Cui Miao
Published: July 2023

In this article, the progress of frequently used advanced numerical methods is presented. According to the discretisation manner and manipulation dimensionality, these methods can be classified into four categories: volume-, surface-, line-, and point-operations–based methods. The volume-operation–based methods described in this article include the finite element method and element differential method; the surface-operation–based methods consist of the boundary element method and finite volume method; the line-operation–based methods cover the finite difference method and finite line method; and the point-operation–based methods mainly include the mesh free method and free element method. These methods have their own distinctive advantages in some specific disciplines. For example, the finite element method is the dominant method in solid mechanics, the finite volume method is extensively used in fluid mechanics, the boundary element method is more accurate and easier to use than other methods in fracture mechanics and infinite media, the mesh free method is more flexible for simulating varying and distorted geometries, and the newly developed free element and finite line methods are suitable for solving multi-physics coupling problems. This article provides a detailed conceptual description and typical applications of these promising methods, focusing on developments in recent years.
Exploring the effects of human-centered AI explanations on trust and reliance
Authors: Scharowski Nicolas , Perrig Sebastian A. C. , Svab Melanie , Opwis Klaus , Brühlmann Florian
Published: July 2023

Transparency is widely regarded as crucial for the responsible real-world deployment of artificial intelligence (AI) and is considered an essential prerequisite to establishing trust in AI. There are several approaches to enabling transparency, with one promising attempt being human-centered explanations. However, there is little research into the effectiveness of human-centered explanations on end-users' trust. What complicates the comparison of existing empirical work is that trust is measured in different ways. Some researchers measure subjective trust using questionnaires, while others measure objective trust-related behavior such as reliance. To bridge these gaps, we investigated the effects of two promising human-centered post-hoc explanations, feature importance and counterfactuals, on trust and reliance. We compared these two explanations with a control condition in a decision-making experiment (N = 380). Results showed that human-centered explanations can significantly increase reliance but the type of decision-making (increasing a price vs. decreasing a price) had an even greater influence. This challenges the presumed importance of transparency over other factors in human decision-making involving AI, such as potential heuristics and biases. We conclude that trust does not necessarily equate to reliance and emphasize the importance of appropriate, validated, and agreed-upon metrics to design and evaluate human-centered AI.
Development and validation of the motivation to publish scale-scientific articles (EMP-AC) for Peruvian university students
Authors: Mamani-Benito Oscar , Torres-Miranda Julio , Apaza-Tarqui Edison Effer , Tito-Betancur Madona , Morales-García Wilter C. , Turpo-Chaparro Josué Edison
Published: July 2023

Objective

To design and validate the motivation to publish scale-scientific articles (EMP-AC) for Peruvian university students.

Methods

This was an instrumental study in which 653 health, business, humanities and engineering students from private and state universities in the 3 regions of Peru participated. The scale was designed in 5 stages following international standards. The internal structure was assessed through both an Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA).

Results

The content analysis by expert judges also supported the representativeness of the items related to the construction. The internal structure of the 13-item scale was confirmed through the Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) which showed a structure of three factors: commitment, behavior, and intentional state as initially proposed. Previous analyses of goodness of fit indices were satisfactory (χ2 (167) = 276.93, p  <  0.001; CFI = 0.95; TLI = 0.93; RMSEA = 0.07 [0.06–0.08]; SRMR = 0.06).

Conclusion

The EMP-AC shows initial evidence of validity and reliability; therefore, it can be applied in the study of the motivation to publish scientific articles by Peruvian university students.
Therapeutic response to pazopanib: case report and literature review on molecular abnormalities of aggressive prolactinomas
Authors: Medina Eduardo J. , Zohdy Youssef M. , Porto Edoardo , Revuelta Barbero Juan M. , Bray David , Maldonado Justin , Rodas Alejandra , Mayol Miguel , Morales Bryan , Neill Stewart , Read William , Pradilla Gustavo , Ioachimescu Adriana , Garzon-Muvdi Tomas
Published: July 2023

Introduction

Aggressive prolactinomas (APRLs) pose a significant clinical challenge due to their high rate of regrowth and potentially life-threatening complications. In this study, we present a case of a patient with an APRL who had a trial of multiple therapeutic modalities with the aim to provide a review of molecular abnormalities and management of APRLs by corroborating our experience with previous literature.

Methods

A total of 268 articles were reviewed and 46 were included. Case reports and series, and studies that investigated the molecular and/or genetic analysis of APRLs were included. Special care was taken to include studies describing prolactinomas that would fall under the APRL subtype according to the European Society of Endocrinology guidelines; however, the author did not label the tumor as “aggressive” or “atypical”. Addiontionally, we present a case report of a 56-year-old man presented with an invasive APRL that was resistant to multiple treatment modalities.

Results

Literature review revealed multiple molecular abnormalities of APRLs including mutations in and/or deregulation of ADAMTS6, MMP-9, PITX1, VEGF, POU6F2, CDKN2A, and Rb genes. Mismatch repair genes, downregulation of microRNAs, and hypermethylation of specific genes including RASSF1A, p27, and MGMT were found to be directly associated with the aggressiveness of prolactinomas. APRL receptor analysis showed that low levels of estrogen receptor (ER) and an increase in somatostatin receptors (SSTR5) and epidermal growth factor receptors (EGFR) were associated with increased invasiveness and higher proliferation activity. Our patient had positive immunohistochemistry staining for PD-L1, MSH2, and MSH6, while microarray analysis revealed mutations in the CDKN2A and POU6F2 genes. Despite undergoing two surgical resections, radiotherapy, and taking dopamine agonists, the tumor continued to progress. The patient was administered pazopanib, which resulted in a positive response and the patient remained progression-free for six months. However, subsequent observations revealed tumor progression. The patient was started on PD-L1 inhibitor pembrolizumab, yet the tumor continued to progress.

Conclusion

APRLs are complex tumors that require a multidisciplinary management approach. Knowledge of the molecular underpinnings of these tumors is critical for understanding their pathogenesis and identifying potential targets for precision medical therapy.
Normalization of puberty and adult height in girls with Turner syndrome: results of the Swedish Growth Hormone trials initiating transition into adulthood
Authors: Kriström Berit , Ankarberg-Lindgren Carina , Barrenäs Marie-Louise , Nilsson Karl Olof , Albertsson-Wikland Kerstin
Published: July 2023

Objective

To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.

Methods

National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3–16 years at GH start during year 1987–1998, with AH in 2003–2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3–9 years (young; n=79) or 9–16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin® Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in heightSDS, AHSDS, and age at PO and at AH were evaluated.

Results

At GH start, heightSDS was −2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose–response in both young and old TS girls; the mean difference was (95%CI) 0.66 (−0.91 to −0.26) and 0.57 (−1.0 to −0.13), respectively. The prepubertal gainSDS (1.3–2.1) was partly lost during puberty (−0.4 to −2.1). Age/heightSDS at PO ranged from 13 years/−0.42 for GH67young to 15.2 years/−1.47 for GH33old. At AH, GH67old group became tallest (17.2 years; 159.9 cm; −1.27 SDS; total gainSDS, 1.55) compared to GH67young group being least delayed (16.1 years; 157.1 cm; −1.73 SDS; total, 1.08). The shortest was the GH33young group (17.3 years; 153.7 cm: −2.28 SDS; total gainSDS, 0.53), and the most delayed was the GH33old group, (18.5 years; 156.5 cm; −1.82 SDS; total gainSDS, 0.98).

Conclusion

For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood.
Development of a prediction model for neonatal hypoglycemia risk factors: a retrospective study
Authors: Wu Tian , Huang Yi-Yan , Song Wei , Redding Sharon R. , Huang Wei-Peng , Ouyang Yan-Qiong
Published: July 2023

Background

It’s challenging for healthcare workers to detect neonatal hypoglycemia due to its rapid progression and lack of aura symptoms. This may lead to brain function impairment for the newborn, placing a significant care burden on the family and creating an economic burden for society. Tools for early diagnosis of neonatal hypoglycemia are lacking. This study aimed to identify newborns at high risk of developing neonatal hypoglycemia early by developing a risk prediction model.

Methods

Using a retrospective design, pairs (470) of women and their newborns in a tertiary hospital from December 2021 to September 2022 were included in this study. Socio-demographic data and clinical data of mothers and newborns were collected. Univariate and multivariate logistic regression were used to screen optimized factors. A neonatal hypoglycemia risk nomogram was constructed using R software, and the calibration curve and receiver operator characteristic curve (ROC) was utilized to evaluate model performance.

Results

Factors integrated into the prediction risk nomogram were maternal age (odds ratio [OR] =1.10, 95% CI: 1.04, 1.17), fasting period (OR=1.07, 95% CI: 1.03, 1.12), ritodrine use (OR=2.00, 95% CI: 1.05, 3.88), gestational diabetes mellitus (OR=2.13, 95% CI: 1.30, 3.50), gestational week (OR=0.80, 95% CI: 0.66, 0.96), fetal distress (OR=1.76, 95% CI: 1.11, 2.79) and neonatal body mass index (OR=1.50, 95% CI: 1.24, 1.84). The area under the curve (AUC) was 0.79 (95% confidence interval [CI]: 0.75, 0.82), specificity was 0.82, and sensitivity was 0.62.

Conclusion

The prediction model of this study demonstrated good predictive performance. The development of the model identifies advancing maternal age, an extended fasting period before delivery, ritodrine use, gestational diabetes mellitus diagnosis, fetal distress diagnosis and an increase in neonatal body mass index increase the probability of developing neonatal hypoglycemia, while an extended gestational week reduces the probability of developing neonatal hypoglycemia.
Prognosis prediction and comparison between pancreatic signet ring cell carcinoma and pancreatic duct adenocarcinoma: a retrospective observational study
Authors: Zhou Hui , Li Xiao-xue , Huang Yun-peng , Wang Yong-xiang , Zou Heng , Xiong Li , Liu Zhong-tao , Wen Yu , Zhang Zi-jian
Published: July 2023

Background

Pancreatic signet ring cell carcinoma (PSRCC) is a rare and aggressive cancer that has been reported primarily as case reports. Due to limited large-scale epidemiological and prognostic analyses, the outcomes of PSRCC patients varies greatly in the absence of recognized first-line treatment strategies. This study aimed to compare the clinical features, treatment, and prognosis of PSRCC and pancreatic ductal cell carcinoma (PDAC), the most common subtype of pancreatic cancer, and to establish predictive models for these subtypes.

Methods

The data on PSRCC and PDAC patients from 1998 to 2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Thereafter, the clinical, demographic, and treatment characteristics of the two groups and the differences and influencing factors of the two groups were evaluated by propensity score matching (PSM), Kaplan–Meier survival curves, Cox risk regression analyses, and least absolute shrinkage and selection operator (LASSO) analysis. Next, prognosis models were constructed and validated by KM and ROC analysis. Finally, a nomogram was constructed, based on the results of these analyses, to predict survival outcomes of PSRCC and PDAC patients.

Results

A total of 84,789 patients (432 PSRCC and 84357 PDAC patients) were included in this study. The results of the study revealed that, compared to the PDAC patients, PSRCC patients were more likely to be male, aged between 58–72 years, have larger tumor masses, and less likely to undergo chemotherapy. Before PSM, the overall survival and cancer-specific survival of the PSRCC group were significantly lower than those PDAC group, but there was no difference in the prognosis of the two groups after PSM. Additionally, lymph node ratio (LNR), log odds of positive lymph node (LODDS), tumor size, age, T-stage, marital status, and summary stage were found to be independent prognostic factors for PSRCC. Lastly, the prediction model and nomogram based on these prognostic factors could accurately predict the survival rate of the patients in SEER datasets and external validation datasets.

Conclusion

The prognosis of PSRCC and PDAC patients is similar under the same conditions; however, PSRCC patients may have more difficulty in receiving better treatment, thus resulting in their poor prognosis.
Field studies of PERC and Al-BSF PV module performance loss using power and I-V timeseries
Authors: Curran Alan J. , Yu Xuanji , Liu Jiqi , Colvin Dylan J. , Iqbal Nafis , Moran Thomas , Brownell Brent , Li Mengjie , Davis Kristopher O. , Huey Bryan D. , Jaubert Jean-Nicolas , Braid Jennifer L. , Bruckman Laura S. , French Roger H.
Published: July 2023

We have studied the degradation of both full-sized modules and minimodules with PERC and Al-BSF cell variations in fields while considering packaging strategies. We demonstrate the implementations of data-driven tools to analyze large numbers of modules and volumes of timeseries data to obtain the performance loss and degradation pathways. This data analysis pipeline enables quantitative comparison and ranking of module variations, as well as mapping and deeper understanding of degradation mechanisms. The best performing module is a half-cell PERC, which shows a performance loss rate (PLR) of −0.27 ± 0.12% per annum (%/a) after initial losses have stabilized. Minimodule studies showed inconsistent performance rankings due to significant power loss contributions via series resistance, however, recombination losses remained stable. Overall, PERC cell variations outperform or are not distinguishable from Al-BSF cell variations.
High-quality RNA extraction and the regulation of genes encoding cellulosomes are correlated with growth stage in anaerobic fungi
Authors: Brown Jennifer L. , Gierke Taylor , Butkovich Lazarina  V. , Swift Candice L. , Singan Vasanth , Daum Christopher , Barry Kerrie , Grigoriev Igor V. , O’Malley Michelle A.
Published: July 2023

Anaerobic fungi produce biomass-degrading enzymes and natural products that are important to harness for several biotechnology applications. Although progress has been made in the development of methods for extracting nucleic acids for genomic and transcriptomic sequencing of these fungi, most studies are limited in that they do not sample multiple fungal growth phases in batch culture. In this study, we establish a method to harvest RNA from fungal monocultures and fungal–methanogen co-cultures, and also determine an optimal time frame for high-quality RNA extraction from anaerobic fungi. Based on RNA quality and quantity targets, the optimal time frame in which to harvest anaerobic fungal monocultures and fungal-methanogen co-cultures for RNA extraction was 2-5 days of growth post-inoculation. When grown on cellulose, the fungal strain Anaeromyces robustus cocultivated with the methanogen Methanobacterium bryantii upregulated genes encoding fungal carbohydrate-active enzymes and other cellulosome components relative to fungal monocultures during this time frame, but expression patterns changed at 24-hour intervals throughout the fungal growth phase. These results demonstrate the importance of establishing methods to extract high-quality RNA from anaerobic fungi at multiple time points during batch cultivation.
Kidney function and cardiovascular diseases: a large-scale observational and Mendelian randomization study
Authors: Hu Chang , Li Yiming , Qian Yaoyao , Wu Zhenying , Hu Bo , Peng Zhiyong
Published: July 2023

Background

Prior observational studies have found an association between kidney function and cardiovascular diseases (CVDs). However, these studies did not investigate causality. Therefore, the aim of this study is to examine the causal relationship between kidney function and CVDs.

Methods

We utilized data from the eICU Collaborative Research Database (eICU-CRD) from the years 2014-2015 to evaluate the observational association between renal failure (RF) and CVDs. To investigate the causal effects of kidney function (estimated glomerular filtration rate [eGFR] and chronic kidney disease [CKD]) and CVDs (including atrial fibrillation [AF], coronary artery disease [CAD], heart failure [HF], any stroke [AS], and any ischemic stroke [AIS]), we conducted a two-sample bidirectional Mendelian randomization (MR) analysis.

Results

In the observational analysis, a total of 157,883 patients were included. After adjusting for potential confounding factors, there was no significant association between baseline RF and an increased risk of developing CVDs during hospitalization [adjusted odds ratio (OR): 1.056, 95% confidence interval (CI): 0.993 to 1.123, P = 0.083]. Conversely, baseline CVDs was significantly associated with an increased risk of developing RF during hospitalization (adjusted OR: 1.189, 95% CI: 1.139 to 1.240, P < 0.001). In the MR analysis, genetically predicted AF was associated with an increased risk of CKD (OR: 1.050, 95% CI: 1.016 to 1.085, P = 0.004). HF was correlated with lower eGFR (β: -0.056, 95% CI: -0.090 to -0.022, P = 0.001). A genetic susceptibility for AS and AIS was linked to lower eGFR (β: -0.057, 95% CI: -0.079 to -0.036, P < 0.001; β: -0.029, 95% CI: -0.050 to -0.009, P = 0.005; respectively) and a higher risk of CKD (OR: 1.332, 95% CI: 1.162 to 1.528, P < 0.001; OR: 1.197, 95% CI: 1.023 to 1.400, P = 0.025; respectively). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of kidney function on CVDs. Outcomes remained consistent in sensitivity analyses.

Conclusion

Our study provides evidence for causal effects of CVDs on kidney function. However, the evidence to support the causal effects of kidney function on CVDs is currently insufficient. Further mechanistic studies are required to determine the causality.
Co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells attenuates human NK cell-mediated degranulation
Authors: Cross-Najafi Arthur A. , Farag Kristine , Isidan Abdulkadir , Li Wei , Zhang Wenjun , Lin Zhansong , Walsh Julia R. , Lopez Kevin , Park Yujin , Higgins Nancy G. , Cooper David K.C. , Ekser Burcin , Li Ping
Published: July 2023

Natural killer (NK) cells play an important role in immune rejection in solid organ transplantation. To mitigate human NK cell activation in xenotransplantation, introducing inhibitory ligands on xenografts via genetic engineering of pigs may protect the graft from human NK cell-mediated cytotoxicity and ultimately improve xenograft survival. In this study, non-classical HLA class I molecules HLA-E and HLA-G were introduced in an immortalized porcine liver endothelial cell line with disruption of five genes (GGTA1, CMAH, β4galNT2, SLA-I α chain, and β-2 microglobulin) encoding three major carbohydrate xenoantigens (αGal, Neu5Gc, and Sda) and swine leukocyte antigen class I (SLA-I) molecules. Expression of HLA-E and/or HLA-G on pig cells were confirmed by flow cytometry. Endogenous HLA-G molecules as well as exogenous HLA-G VL9 peptide could dramatically enhance HLA-E expression on transfected pig cells. We found that co-expression of HLA-E and HLA-G on porcine cells led to a significant reduction in human NK cell activation compared to the cells expressing HLA-E or HLA-G alone and the parental cell line. NK cell activation was assessed by analysis of CD107a expression in CD3-CD56+ population gated from human peripheral blood mononuclear cells. CD107a is a sensitive marker of NK cell activation and correlates with NK cell degranulation and cytotoxicity. HLA-E and/or HLA-G on pig cells did not show reactivity to human sera IgG and IgM antibodies. This in vitro study demonstrated that co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells provided a superior inhibition in human xenoreactive NK cells, which may guide further genetic engineering of pigs to prevent human NK cell mediated rejection.
Tertiary lymphoid structures in pancreatic cancer: a new target for immunotherapy
Authors: Zou Xinlei , Guan Canghai , Gao Jianjun , Shi Wujiang , Cui Yunfu , Zhong Xiangyu
Published: July 2023

Pancreatic cancer (PC) is extremely malignant and shows limited response to available immunotherapies due to the hypoxic and immunosuppressive nature of its tumor microenvironment (TME). The aggregation of immune cells (B cells, T cells, dendritic cells, etc.), which is induced in various chronic inflammatory settings such as infection, inflammation, and tumors, is known as the tertiary lymphoid structure (TLS). Several studies have shown that TLSs can be found in both intra- and peritumor tissues of PC. The role of TLSs in peritumor tissues in tumors remains unclear, though intratumoral TLSs are known to play an active role in a variety of tumors, including PC. The formation of intratumoral TLSs in PC is associated with a good prognosis. In addition, TLSs can be used as an indicator to assess the effectiveness of treatment. Targeted induction of TLS formation may become a new avenue of immunotherapy for PC. This review summarizes the formation, characteristics, relevant clinical outcomes, and clinical applications of TLSs in the pancreatic TME. We aim to provide new ideas for future immunotherapy of PC.
Treatment and survival analysis for 40-year SEER data on upper esophageal cancer
Authors: Wu Xi , Zhu Ming-Chuang , Li Guo-Liang , Xiong Peng , Sun Wei , Zhang Ni , Zhao Bo , Li Le-Qun , Fu Xiang-Ning , Zhu Min
Published: July 2023

Background

Upper esophageal cancer (UEC) is rare in both Eastern and Western countries. The epidemiological characteristics and long-term survival of UEC patients are less known. In addition, the choice of optimal treatment for UEC has been controversial.

Methods

Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected using the SEER database. Student's t-test and Pearson's chi-square test were used to compare the differences in parameters among different groups. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rates were calculated by using the Kaplan–Meier method. Cox proportional hazard regression was used to analyze predictive factors.

Results

In the past 40 years, the cases of UEC have gradually increased, and the proportion of adenocarcinoma (AD) has gradually increased (from 3.6% to 11.8%, p < 0.001). There has been a significant increase (1973–1982 vs. 2004–2013) in median OS (7 months vs. 10 months, p < 0.001) and median ECSS (7 months vs. 11 months, p < 0.001) among UEC patients from 1973 to 2013. For the impact of different treatments, the results showed that the ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). Subgroup analysis showed that ECSS and OS were highest among patients treated with SWR compared with R+S and RWS for patients with localized disease. For regional disease, ECSS and OS were highest among patients with R+S compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC.

Conclusion

Although the long-term survival of UEC remains poor, it has gradually increased since 1973. This should be closely related to the improvement of medical care over the past 40 years. Different treatment methods have a great influence on the long-term survival of UEC. For localized diseases, surgery may be a better choice. For regional disease, surgery plus adjuvant or neoadjuvant radiotherapy may be more beneficial to improve the long-term prognosis of UEC patients.
Short-term outcome of patients with adult IgA vasculitis: a single-center experience
Authors: Hočevar Alojzija , Ostrovršnik Jaka , Jurčić Vesna , Tomšič Matija , Rotar Žiga
Published: July 2023

Background

Follow-up data on IgA vasculitis (IgAV) in adults are scarce. We aimed to investigate the outcome of adult IgAV in a well-defined cohort.

Methods

Data from histologically proven patients diagnosed between January 2010 and July 2022 with at least a 3-month follow-up were analyzed. The frequency and type of relapses and information on kidney function were extracted. Risk factors for IgAV relapse and decline in renal function were studied using the Cox hazards regression analysis. Mortality in IgAV was assessed using the Kaplan–Meier analysis and the standardized mortality ratio (SMR).

Results

In total, 265 patients were followed for a median of 24 months. At baseline, 38.9, 29.8, and 44.5% had articular, gastrointestinal, and renal involvement, respectively. Initially, 189 (71.3%) patients received systemic glucocorticoids, and 32 (12.1%) patients received an additional immunomodulator. During follow-up, 42 (15.8%) patients relapsed. Relapses were more common in younger patients (HR 1.03 [95%CI 1.01–1.05]) and those without baseline glucocorticoid treatment (HR 3.70 [95%CI 2.0–6.67]). Furthermore, 74 (27.9%) patients had persistent abnormal urinalysis and a substantial (≥20%) decline in glomerular filtration rate (eGFR) was recorded in 41 (15.5%) patients. The factors associated with persistent abnormal urinalysis were an absence of IgAV joint involvement and baseline immunomodulatory treatment. Pre-existent chronic kidney disease and heart failure were associated with eGFR decline. The overall SMR was 1.4 (95%CI 1.14–1.71) compared to the Slovenian general population.

Conclusion

IgAV relapses occurred in 15% of patients, with younger patients with symptomatically managed IgAV experiencing it more frequently. Heart failure emerged as a predictor of persistent abnormal urinalysis and a decline in eGFR. Adults with IgAV had increased mortality compared to the general population.
Efficacy and safety of parecoxib and flurbiprofen axetil for perioperative analgesia in children: a network meta-analysis
Authors: Chen Xi , Chen Pan , Chen Xiao , Huang Min , Tang Kejing , He Qiuyi
Published: July 2023

Objective

The aim of this study was to systematically review the efficacy and safety of parecoxib and flurbiprofen axetil for perioperative analgesia in children through Bayesian network meta-analysis.

Methods

We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, VIP, and Wanfang Data databases on 18 July 2022 to obtain randomized controlled trials comparing perioperative parecoxib or flurbiprofen with placebo or standard treatment for pediatric analgesia. The outcomes were the postoperative pain score and the incidence of adverse events. The Gemtc package of R-4.0.3 and Stata 17.0 were used for Bayesian network meta-analysis.

Results

We retrieved 942 articles and 49 randomized controlled trials involving 3,657 patients who met the inclusion criteria. Compared with children who received placebo treatment, those who received flurbiprofen axetil had lower pain sores at each time point within 24 h postoperatively, and those who received parecoxib had lower pain sores at each time point within 12 h postoperatively. Compared with children who received tramadol treatment, both the children who received flurbiprofen axetil or parecoxib had lower pain scores at 8 h postoperatively. The ranking results demonstrated that flurbiprofen axetil had significant superiority in reducing pain scores at 2, 4, and 12 h postoperatively, and parecoxib had significant superiority in reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively. In terms of safety, compared with children who received placebo, those who received flurbiprofen axetil or parecoxib had a lower incidence of total adverse events and postoperative agitation. Compared with tramadol, flurbiprofen axetil and parecoxib both significantly reduced the incidence of total adverse events and postoperative nausea and vomiting. Compared with flurbiprofen axetil or fentanyl, parecoxib significantly reduced the incidence of postoperative nausea and vomiting. The ranking results showed that parecoxib was advantageous in decreasing the incidence of total adverse events and postoperative nausea and vomiting.

Conclusion

Flurbiprofen axetil was most effective at reducing pain scores at 2, 4, and 12 h postoperatively. Parecoxib had an advantage in terms of reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively, as well as the incidence of total adverse events and postoperative nausea and vomiting.

Systematic trial registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=348886, PROSPERO (CRD42022348886).
Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses
Authors: Lumeij Lucas B. , van Huijstee Aile N. , Cappaert Natalie L. M. , Kessels Helmut W.
Published: July 2023

Our knowledge on synaptic transmission in the central nervous system has often been obtained by evoking synaptic responses to populations of synapses. Analysis of the variance in synaptic responses can be applied as a method to predict whether a change in synaptic responses is a consequence of altered presynaptic neurotransmitter release or postsynaptic receptors. However, variance analysis is based on binomial statistics, which assumes that synapses are uniform. In reality, synapses are far from uniform, which questions the reliability of variance analysis when applying this method to populations of synapses. To address this, we used an in silico model for evoked synaptic responses and compared variance analysis outcomes between populations of uniform versus non-uniform synapses. This simulation revealed that variance analysis produces similar results irrespectively of the grade of uniformity of synapses. We put this variance analysis to the test with an electrophysiology experiment using a model system for which the loci of plasticity are well established: the effect of amyloid-β on synapses. Variance analysis correctly predicted that postsynaptically produced amyloid-β triggered predominantly a loss of synapses and a minor reduction of postsynaptic currents in remaining synapses with little effect on presynaptic release probability. We propose that variance analysis can be reliably used to predict the locus of synaptic changes for populations of non-uniform synapses.
Identification of a miRNA–mRNA regulatory network for post-stroke depression: a machine-learning approach
Authors: Qiu Huaide , Shen Likui , Shen Ying , Mao Yiming
Published: July 2023

Objective

The study aimed to explore the miRNA and mRNA biomarkers in post-stroke depression (PSD) and to develop a miRNA–mRNA regulatory network to reveal its potential pathogenesis.

Methods

The transcriptomic expression profile was obtained from the GEO database using the accession numbers GSE117064 (miRNAs, stroke vs. control) and GSE76826 [mRNAs, late-onset major depressive disorder (MDD) vs. control]. Differentially expressed miRNAs (DE-miRNAs) were identified in blood samples collected from stroke patients vs. control using the Linear Models for Microarray Data (LIMMA) package, while the weighted correlation network analysis (WGCNA) revealed co-expressed gene modules correlated with the subject group. The intersection between DE-miRNAs and miRNAs identified by WGCNA was defined as stroke-related miRNAs, whose target mRNAs were stroke-related genes with the prediction based on three databases (miRDB, miRTarBase, and TargetScan). Using the GSE76826 dataset, the differentially expressed genes (DEGs) were identified. Overlapped DEGs between stroke-related genes and DEGs in late-onset MDD were retrieved, and these were potential mRNA biomarkers in PSD. With the overlapped DEGs, three machine-learning methods were employed to identify gene signatures for PSD, which were established with the intersection of gene sets identified by each algorithm. Based on the gene signatures, the upstream miRNAs were predicted, and a miRNA–mRNA network was constructed.

Results

Using the GSE117064 dataset, we retrieved a total of 667 DE-miRNAs, which included 420 upregulated and 247 downregulated ones. Meanwhile, WGCNA identified two modules (blue and brown) that were significantly correlated with the subject group. A total of 117 stroke-related miRNAs were identified with the intersection of DE-miRNAs and WGCNA-related ones. Based on the miRNA-mRNA databases, we identified a list of 2,387 stroke-related genes, among which 99 DEGs in MDD were also embedded. Based on the 99 overlapped DEGs, we identified three gene signatures (SPATA2, ZNF208, and YTHDC1) using three machine-learning classifiers. Predictions of the three mRNAs highlight four miRNAs as follows: miR-6883-5p, miR-6873-3p, miR-4776-3p, and miR-6738-3p. Subsequently, a miRNA–mRNA network was developed.

Conclusion

The study highlighted gene signatures for PSD with three genes (SPATA2, ZNF208, and YTHDC1) and four upstream miRNAs (miR-6883-5p, miR-6873-3p, miR-4776-3p, and miR-6738-3p). These biomarkers could further our understanding of the pathogenesis of PSD.
Quality appraisal of clinical practice guidelines for motor neuron diseases or related disorders using the AGREE II instrument
Authors: Ou Jia-Yin , Liu Jun-Jun , Xu Jing , Li Jia-Yu , Liu Yang , Liu You-Zhang , Lu Li-Ming , Pan Hua-Feng , Wang Lin
Published: July 2023

Objectives

This study aimed to systematically assess the quality of CPGs for motor neuron diseases (MNDs) or related disorders and identify the gaps that limit evidence-based practice.

Methods

Four scientific databases and six guideline repositories were searched for eligible CPGs. Three researchers assessed the eligible CPGs using the Appraisal of Guidelines Research and Evaluation II instrument. The distribution of the level of evidence and strength of recommendation of these CPGs were determined. The univariate regression analysis was used to explore the characteristic factors affecting the quality of CPGs.

Results

Fifteen CPGs met the eligibility criteria: 10 were for MND and 5 were for spinal muscular atrophy. The mean overall rating score was 44.5%, and only 3 of 15 CPGs were of high quality. The domains that achieved low mean scores were applicability (24.4%), rigor of development (39.9%), and stakeholder involvement (40.3%). Most recommendations were based on low-quality evidence and had a weak strength. The CPGs that were updated, meant for adults, and evidence based, and used a CPG quality tool and a grading system were associated with higher scores in certain specific domains and overall rating.

Conclusion

The overall quality of CPGs for MNDs or related disorders was poor and recommendations were largely based on low-quality evidence. Many areas still need improvement to develop high-quality CPGs, and the use of CPG quality tools should be emphasized. A great deal of research on MNDs or related disorders is still needed to fill the large evidence gap.
Case study: persistent recovery of hand movement and tactile sensation in peripheral nerve injury using targeted transcutaneous spinal cord stimulation
Authors: Chandrasekaran Santosh , Bhagat Nikunj A. , Ramdeo Richard , Ebrahimi Sadegh , Sharma Pawan D. , Griffin Doug G. , Stein Adam , Harkema Susan J. , Bouton Chad E.
Published: July 2023

Peripheral nerve injury can lead to chronic pain, paralysis, and loss of sensation, severely affecting quality of life. Spinal cord stimulation has been used in the clinic to provide pain relief arising from peripheral nerve injuries, however, its ability to restore function after peripheral nerve injury have not been explored. Neuromodulation of the spinal cord through transcutaneous spinal cord stimulation (tSCS), when paired with activity-based training, has shown promising results towards restoring volitional limb control in people with spinal cord injury. We show, for the first time, the effectiveness of targeted tSCS in restoring strength (407% increase from 1.79 ± 1.24 N to up to 7.3 ± 0.93 N) and significantly increasing hand dexterity in an individual with paralysis due to a peripheral nerve injury (PNI). Furthermore, this is the first study to document a persisting 3-point improvement during clinical assessment of tactile sensation in peripheral injury after receiving 6 weeks of tSCS. Lastly, the motor and sensory gains persisted for several months after stimulation was received, suggesting tSCS may lead to long-lasting benefits, even in PNI. Non-invasive spinal cord stimulation shows tremendous promise as a safe and effective therapeutic approach with broad applications in functional recovery after debilitating injuries.
Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
Authors: Imamura Yukio , Matsumoto Hisatake , Imamura Jun , Matsumoto Naoya , Yamakawa Kazuma , Yoshikawa Nao , Murakami Yuki , Mitani Satoko , Nakagawa Junichiro , Yamada Tomoki , Ogura Hiroshi , Oda Jun , Shimazu Takeshi
Published: July 2023

Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1β (IL-1β) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1β levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1β levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.
Effects of exercise based on ACSM recommendations on bone mineral density in individuals with osteoporosis: a systematic review and meta-analyses of randomized controlled trials
Authors: Cui Wenlai , Li Dong , Jiang Yueshuai , Gao Yang
Published: July 2023

Purpose: To analyze the effects of different exercise dose on lumbar spine and femoral neck bone mineral density (BMD) in individuals with osteoporosis (OP).

Design: A systematic search was conducted in four electronic databases, namely, PubMed, Embase, Web of Science, and Cochrane, with the topic of the impact of exercise on BMD in individuals with OP. Randomized controlled trials comparing exercise intervention with no intervention were identified, and changes in lumbar spine and femoral neck BMD were reported and evaluated using standardized mean difference (SMD) and 95% confidence interval (95% CI). The intervention measures in the studies were evaluated and categorized as high adherence with the exercise testing and prescription recommendations for individuals with OP developed by the American College of Sports Medicine (ACSM) or low/uncertainty adherence with ACSM recommendations. A random effects model was used to conduct meta-analyses and compare the results between subgroups.

Results: A total of 32 studies involving 2005 participants were included in the analyses, with 14 studies categorized as high adherence with ACSM recommendations and 18 studies categorized as low or uncertain adherence. In the analyses of lumbar spine BMD, 27 studies with 1,539 participants were included. The combined SMD for the high adherence group was 0.31, while the combined SMD for the low or uncertain adherence group was 0.04. In the analyses of femoral neck BMD, 23 studies with 1,606 participants were included. The combined SMD for the high adherence group was 0.45, while the combined SMD for the low or uncertain adherence group was 0.28. Within resistance exercise, the subgroup with high ACSM adherence had a greater impact on lumbar spine BMD compared to the subgroup with low or uncertain ACSM adherence (SMD: 0.08 > −0.04). Similarly, for femoral neck BMD, resistance exercise with high ACSM adherence had a higher SMD compared to exercise with low or uncertain ACSM adherence (SMD: 0.49 > 0.13).

Conclusion: The results suggest that exercise interventions with high adherence to ACSM recommendations are more effective in improving lumbar spine and femoral neck BMD in individuals with OP compared to interventions with low or uncertain adherence to ACSM recommendations.

Systematic Review Registration: PROSPERO, identifier CRD42023427009