bluuebunny/crossref_metadata_2025 huggingface dataset:
PELATIHAN KEWIRAUSAHAAN PRODUKSI KERAJINAN TANGAN HOME DÉCOR SERTA OPTIMALISASI PEMASARAN PRODUK MELALUI SOSIAL MEDIA DAN MARKET PLACE PADA IBU-IBU PKK KEC. AMPELGADING KAB. MALANG
Authors: Ernawati Widi Dwi , Oktavia Fathimatus Zahro Fazda , Akbar Dharmawan Iqbal , Maula Farisa Nur , Selviana Vuvut
Published: January 2023

Kaum perempuan dalam masyarakat bisa menjadi satu indikator untuk meningkatkan kesejahteraan dan PKK adalah suatu wadah organisasi perempuan. Ibu-ibu PKK Kecamatan Ampelgading mempunyai latar belakang pendidikan yang sangat bervariasi dengan perekonomian keluarga menengah ke bawah. Dewasa ini, perkembangan teknologi menjadi tantangan tersendiri bagi ibu-ibu. Jika ibu-ibu mampu mengoptimalkan perkembangan teknologi yang dimiliki maka bisa meningkatkan kesejahteraan keluarga mereka. Keterampilan yang dimiliki bisa dikolaborasikan dengan kemandirian mereka untuk dapat mengembangkan berbagai macam peluang usaha. Oleh karena itu, dengan masalah dan potensi yang dimiliki oleh ibu-ibu PKK Ampelgading, pelatihan kewirausahaan produksi kerajinan tangan home décor serta optimalisasi pemasaran produk melalui sosial media dan market place pada ibu-ibu PKK Kecamatan  Ampelgading, Kabupaten Malang diharapkan bisa menjadi solusi sehingga dapat meningkatkan taraf kesejahteraan ibu-ibu PKK tersebut.
ВЛИЯНИЕ СОЦИО-ЭКОНОМИЧЕСКИХ И КУЛЬТУРНЫХ ФАКТОРОВ НА РОСТ И РАЗВИТИЕ ДЕТЕЙ В ВОЗРАСТЕ ОТ 0 ДО 1 ГОДА В ПАКИСТАНЕ
Authors: Баканова Екатерина
Published: January 2023

The weight of newborns in Pakistan is usually kept at the lower limit
of the norm (2.5-3 kg), which is associated with both the peculiarities of the
constitution of Pakistani women and the peculiarities of their life and nutrition.
However, by the age of 1 year, there is a sharp stratification of children in height
and weight: children in wealthy families most often suffer from increased weight
(and even obesity), children from lower social groups - from malnutrition, both
qualitative and quantitative. This phenomenon is associated both with medical
problems and the system of organization of medical pediatric care in the country,
as well as with socio-economic and cultural factors, such as: the availability of
baby food, the culture of baby food, cultural traditions of the region, the level
of family education, and others. According to the study, recommendations are
made to regulate medical, socio-economic and cultural factors for the optimal
development and growth of children in Pakistan.
Clinical adoptive regulatory T Cell therapy: State of the art, challenges, and prospective
Authors: Amini Leila , Kaeda Jaspal , Fritsche Enrico , Roemhild Andy , Kaiser Daniel , Reinke Petra
Published: January 2023

Rejection of solid organ transplant and graft versus host disease (GvHD) continue to be challenging in post transplantation management. The introduction of calcineurin inhibitors dramatically improved recipients’ short-term prognosis. However, long-term clinical outlook remains poor, moreover, the lifelong dependency on these toxic drugs leads to chronic deterioration of graft function, in particular the renal function, infections and de-novo malignancies. These observations led investigators to identify alternative therapeutic options to promote long-term graft survival, which could be used concomitantly, but preferably, replace pharmacologic immunosuppression as standard of care. Adoptive T cell (ATC) therapy has evolved as one of the most promising approaches in regenerative medicine in the recent years. A range of cell types with disparate immunoregulatory and regenerative properties are actively being investigated as potential therapeutic agents for specific transplant rejection, autoimmunity or injury-related indications. A significant body of data from preclinical models pointed to efficacy of cellular therapies. Significantly, early clinical trial observations have confirmed safety and tolerability, and yielded promising data in support of efficacy of the cellular therapeutics. The first class of these therapeutic agents commonly referred to as advanced therapy medicinal products have been approved and are now available for clinical use. Specifically, clinical trials have supported the utility of CD4+CD25+FOXP3+ regulatory T cells (Tregs) to minimize unwanted or overshooting immune responses and reduce the level of pharmacological immunosuppression in transplant recipients. Tregs are recognized as the principal orchestrators of maintaining peripheral tolerance, thereby blocking excessive immune responses and prevent autoimmunity. Here, we summarize rationale for the adoptive Treg therapy, challenges in manufacturing and clinical experiences with this novel living drug and outline future perspectives of its use in transplantation.
Cartilage organoids for cartilage development and cartilage-associated disease modeling
Authors: Lin Weiping , Wang Min , Xu Liangliang , Tortorella Micky , Li Gang
Published: January 2023

Cartilage organoids have emerged as powerful modelling technology for recapitulation of joint embryonic events, and cartilage regeneration, as well as pathophysiology of cartilage-associated diseases. Recent breakthroughs have uncovered “mini-joint” models comprising of multicellular components and extracellular matrices of joint cartilage for development of novel disease-modifying strategies for personalized therapeutics of cartilage-associated diseases. Here, we hypothesized that LGR5-expressing embryonic joint chondroprogenitor cells are ideal stem cells for the generation of cartilage organoids as “mini-joints” ex vivo “in a dish” for embryonic joint development, cartilage repair, and cartilage-associated disease modelling as essential research models of drug screening for further personalized regenerative therapy. The pilot research data suggested that LGR5-GFP-expressing embryonic joint progenitor cells are promising for generation of cartilage organoids through gel embedding method, which may exert various preclinical and clinical applications for realization of personalized regenerative therapy in the future.
Fungal keratitis in Iran: Risk factors, clinical features, and mycological profile
Authors: Soleimani Mohammad , Izadi Alireza , Khodavaisy Sadegh , Santos Claudy Oliveira dos , Tehupeiory-Kooreman Marlou C. , Ghazvini Roshanak Daie , Hashemi Seyed Jamal , Mousavi Seyed Amin Ayatollahi , Aala Farzad , Abdorahimi Mahsa , Aminizadeh Mehdi , Abedinifar Zohre , Mahmoudi Shahram , Mohamadi Afsaneh , Rezaie Sara , Verweij Paul E.
Published: January 2023

Introduction

This study was intended to investigate the clinical features and predisposing factors of fungal keratitis (FK), as well as molecular identification and antifungal susceptibility of causative agents in Tehran, Iran.

Methods

This cross-sectional study was carried out from April 2019 to May 2021. All fungi isolates were identified using conventional methods and were confirmed by DNA-PCR-based molecular assays. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) was used to identify yeast species. Minimum inhibitory concentrations (MIC) of eight antifungal agents were assessed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) microbroth dilution reference method.

Results

Fungal etiology was confirmed in 86 (7.23%) of 1189 corneal ulcers. A significant predisposing factor for FK was ocular trauma caused by plant materials. Therapeutic penetrating keratoplasty (PKP) was required in 60.4% of cases. The predominant fungal species isolated was Fusarium spp. (39.5%) followed by Aspergillus spp. (32.5%) and Candida spp. (16.2%).

Discussion

The MIC results indicate that amphotericin B may be appropriate for treating FK caused by Fusarium species. FK caused by Candida spp. can be treated with flucytosine, voriconazole, posaconazole, miconazole, and caspofungin. In developing countries such as Iran, corneal infection due to filamentous fungi is a common cause of corneal damage. In this region, fungal keratitis is observed primarily within the context of agricultural activity and subsequent ocular trauma. Fungal keratitis can be managed better with understanding the ”local“ etiologies and antifungal susceptibility patterns.
Triglyceride-glucose index for the detection of subclinical heart failure with preserved ejection fraction in patients with type 2 diabetes
Authors: Wang Tingting , Xu Jiani , Zhang Hong , Tao Lichan , Huang Xiaolin
Published: January 2023

Objectives

The triglyceride-glucose (TyG) index has been identified as a reliable and simple surrogate of insulin resistance. In this study, we sought to determine the association between TyG index and cardiac function among asymptomatic individuals with type 2 diabetes (T2DM) without history of any cardiovascular disease.

Materials and methods

The cross-sectional study enrolled 180 T2DM patients without cardiac symptoms. Heart failure with preserved ejection fraction (HFpEF) was defined as Heart Failure Association (HFA)-PEFF score ≥ 5 points.

Results

A total of 38 (21.1%) diabetic patients were identified with HFpEF. Compared with the low-TyG group (TyG index <9.47), patients in high-TyG group (TyG index ≥9.47) showed increased risk of metabolic syndrome and diastolic dysfunction (p < 0.05 for each). Furthermore, after adjustment of confounding variables, the TyG index showed positive correlation with risk factors of metabolic syndrome (including BMI, waist circumference, blood pressure, HbA1c, TG, TC, non-HDL-C, and fasting blood glucose, p < 0.05 for each) and parameters of diastolic dysfunction (E/e’ ratio, p < 0.0001) in patients with T2DM. Moreover, Receiver Operating Characteristic curve analysis showed that the TyG index could be better to predict the risk of suspected HFpEF than other indicators (AUC: 0.706, 95% CI: 0.612–0.801). According, on multiple regression analysis, TyG index was independently correlated with the incidence of HFpEF (odds ratio: 0.786, p = 0.0019), indicating that TyG index could be a reliable biomarker to predict the risk of HFpEF.

Conclusion

The TyG index showed a positive correlation with the risk of subclinical HFpEF in patients with T2DM, providing a new marker to predict and treat HFpEF in diabetes.
Structural changes in silicate melt: A record from high-field strength elements in the Himalayan Cenozoic leucogranites
Authors: Gao Li-E. , Zeng Lingsen , Yan Lilong , Zhao Linghao , Wang Yaying
Published: January 2023

Most Himalayan Cenozoic leucogranites are peraluminous magmas that have experienced various degrees of fractional crystallization. These leucogranites are characterized by relatively high degrees of heterogeneity in their elemental compositions. As the melt’s Zr/Hf ratio passes ∼20, there is an apparent change from positive to negative in the correlation between Zr (or Hf) and Zr/Hf ratio. As Nb/Ta ratio passes ∼5, Nb first decreases and then increases, but Ta first slowly increases and then drastically increases. Such systematic geochemical variations are related to changes in the dissolution behavior of key accessory phases, which are the consequence of silicate melt structural changes associated with fractional crystallization and. As a granitic magma evolves, changes in the melt structure as shown by changes in the compositional parameters (e.g., NBO/T, A/CNK, and M/F) as well as in Zr/Hf and Nb/Ta ratios. When the melt’s Zr/Hf and Nb/Ta ratio passes 20 and 5, respectively, NBO/T, M/F, and A/CNK first decrease and then increase; A/NK and C/NK first decrease and then become nearly constant; Na/K first becomes nearly constant and then increases. Moreover, a substantial change in the melt structure leads to a decrease in granitic viscosity, which in turn fractional crystallization of the granitic melts. Finally, such changes result in the mineralization of economically relevant rare elements in the Himalayan Cenozoic leucogranites.
Sepsis as an independent risk factor in atrial fibrillation and cardioembolic stroke
Authors: Leng Yiming , Li Yalan , Wang Jie , Deng Peizhi , Wang Wei , Wu Jingjing , Wang Wenjuan , Weng Chunyan
Published: January 2023

Background

Electrolyte balance is an important factor to sustain the homeostasis of human body environment and in sepsis pathogenesis. Many current cohort-based studies have already revealed that electrolyte disorder may intensify sepsis and induce stroke. However, the corresponding randomized controlled trials did not show that electrolyte disorder in sepsis has a harmful effect on stroke.

Objectives

The aim of this study was to examine the association of genetically sepsis-derived electrolyte disorder with stroke risk using meta-analysis and Mendelian randomization.

Results

In four studies (182,980 patients), electrolyte disorders were compared with stroke incidence in patients with sepsis. The pooled odds ratio (OR) of stroke is 1.79 [95% confidence interval (CI): 1.23–3.06; p < 0.05], which shows a significant association between electrolyte disorder and stroke in sepsis patients. Furthermore, in order to evaluate the causal association between stroke risk and sepsis-derived electrolyte disorder, a two-sample Mendelian randomization (MR) study was conducted. The genetic variants extracted from a genome-wide association study (GWAS) of exposure data that are strongly associated with frequently used sepsis were used as instrumental variables (IVs). Based on the IVs’ corresponding effect estimates, we estimated overall stroke risk, cardioembolic stroke risk, and stroke induced by large/small vessels from a GWAS meta-analysis with 10,307 cases and 19,326 controls. As a final step to verify the preliminary MR results, we performed sensitivity analysis using multiple types of Mendelian randomization analysis.

Conclusion

Our study revealed the association between electrolyte disorder and stroke in sepsis patients, and the correlation between genetic susceptibility to sepsis and increased risk of cardioembolic stroke, hinting that cardiogenic diseases and accompanying electrolyte disorder interference in due course could help sepsis patients get more benefits in stroke prevention.
Therapeutic efficacy of platinum/etoposide regimens in the treatment of advanced poorly differentiated neuroendocrine carcinomas of the lung: A retrospective analysis
Authors: Puliafito Ivana , Chillari Federico , Russo Alessandro , Cantale Ornella , Sciacca Dorotea , Castorina Luigi , Colarossi Cristina , Franchina Tindara , Vitale Maria Paola , Ricciardi Giuseppina Rosaria Rita , Adamo Vincenzo , Esposito Francesca , Giuffrida Dario
Published: January 2023

Background

Lung neuroendocrine neoplasms (NENs) are rare malignancies developed from bronchial mucosa. Because of its rarity and complex histopathology, there is limited data on the role of chemotherapy in this subset of tumors. Few studies regarding the treatment of poorly differentiated lung NENs, known as neuroendocrine carcinomas (NECs), are available and many limits are detectable as heterogeneity of tumor samples including different origins and different clinical behaviors, moreover, no evidence of therapeutic advances have been achieved along the last thirty years.

Method

We performed a retrospective analysis of 70 patients affected by poorly differentiated lung NECs: half of patients underwent a first line therapy with a combination of cisplatin plus etoposide; the remaining patients receiving carboplatin instead of cisplatin, plus etoposide. Results: In our analysis, the outcomes of patients treated with either cisplatin or carboplatin schedule are similar in terms of ORR (44% versus 33%), DCR (75% versus 70%), PFS (6.0 versus 5.0 months) and OS (13.0 versus 10 months). Median number of chemotherapy cycles was 4 (range 1-8). The 18% of patients required a dose reduction. Main toxicities reported were hematological (70.5%), gastrointestinal (26.5%) and fatigue (18%).

Conclusion

Survival rate in our study suggests that high grade lung NENs are characterized by an aggressive behavior and a poor prognosis, despite the treatment with platinum/etoposide according to available data. Clinical results of present study contribute to strengthen available data on the usefulness of platinum/etoposide regimen in the treatment of poorly differentiated lung NENs
Impact of endocrine disrupting chemicals and pharmaceuticals on Sertoli cell development and functions
Authors: Corpuz-Hilsabeck Maia , Culty Martine
Published: January 2023

Sertoli cells play essential roles in male reproduction, from supporting fetal testis development to nurturing male germ cells from fetal life to adulthood. Dysregulating Sertoli cell functions can have lifelong adverse effects by jeopardizing early processes such as testis organogenesis, and long-lasting processes such as spermatogenesis. Exposure to endocrine disrupting chemicals (EDCs) is recognized as contributing to the rising incidence of male reproductive disorders and decreasing sperm counts and quality in humans. Some drugs also act as endocrine disruptors by exerting off-target effects on endocrine tissues. However, the mechanisms of toxicity of these compounds on male reproduction at doses compatible with human exposure are still not fully resolved, especially in the case of mixtures, which remain understudied. This review presents first an overview of the mechanisms regulating Sertoli cell development, maintenance, and functions, and then surveys what is known on the impact of EDCs and drugs on immature Sertoli cells, including individual compounds and mixtures, and pinpointing at knowledge gaps. Performing more studies on the impact of mixtures of EDCs and drugs at all ages is crucial to fully understand the adverse outcomes these chemicals may induce on the reproductive system.
Association between preconception anti-androgen therapy and pregnancy outcomes of patients with PCOS: A prospective cohort study
Authors: Zhang Xiaowei , Miao Huazhang , Zhou Jiahe , Chen Yuan , Ou Yanlan , Song Yue , Peng Xiuhong , Li Yuancheng , Li Li
Published: January 2023

Background

Polycystic ovary syndrome (PCOS) not only increases fertility challenges for women of reproductive age, but also leads to increased complications during pregnancy and even affects the birth weight of newborns. Also, hyperandrogenemia is associated with lower pregnancy rates and lower live birth rates and may even play a role in preterm delivery and pre-eclampsia in patients with PCOS. However, it is still controversial whether PCOS patients are treated with androgen-lowering therapy before pregnancy.

Objective

To assess the effect of anti-androgen therapy prior to ovulation induction on maternal and infant pregnancy outcomes in patients with PCOS.

Methods

Prospective cohort study.

Results

A total of 296 patients with PCOS were enrolled in the study. The prevalence of adverse pregnancy outcomes, and neonatal complications was lower in DRSP(with drospirenone ethinyl estradiol tablets (II) pretreatment) group than in NO-DRSP(without drospirenone ethinyl estradiol tablets (II) pretreatment) groups (DRSP vs. NO-DRSP: adverse pregnancy outcomes, 12.16% vs. 27.03%, P=0.001; neonatal complications, 17.16% vs. 36.67%, P<0.001). No significant difference was found in maternal complications. Further subgroup analysis revealed that PCOS with pretreatment decreased the risk of preterm delivery (2.99% vs. 10.00%; Adjusted RR, 3.80; 95% CI, 1.19-12.13), pregnancy loss (9.46% vs. 18.92%; Adjusted RR, 2.07; 95% CI, 1.08-3.96), low birth weight (0.75% vs 7.50%; Adjusted RR, 12.08; 95% CI, 1.50-97.31), fetal malformations(1.49% vs. 8.33%; Adjusted RR, 5.63; 95% CI, 1.20-26.33).There were no significant differences in the incidence of DM and PIH as pregnancy complications between the two groups (P>0.05).

Conclusion

Our findings suggest that preconception androgen-lowering therapy in patients with PCOS improves pregnancy outcomes and reduces neonatal complications.
Long noncoding RNA MyD88 functions as a promising diagnostic biomarker in hepatocellular carcinoma
Authors: Wang Zhihuai , Gao Peng , Sun Weijun , Rehman Adeel ur , Jiang Jiakai , Xu Suobao , Xue Cailin , Zhu Chunfu , Qin Xihu
Published: January 2023

Background

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies. Alpha-fetoprotein (AFP) has some limitations in diagnosing early HCC. Recently, long noncoding RNAs (lncRNAs) showed great potential as tumor diagnostic biomarkers, and lnc-MyD88 was previously identified as a carcinogen in HCC. Here, we explored its diagnostic value as a plasma biomarker.

Materials and methods

Quantitative real-time PCR was adopted to detect lnc-MyD88 expression in plasma samples of 98 HCC patients, 52 liver cirrhosis (LC) patients, and 105 healthy people. The correlation between lnc-MyD88 and clinicopathological factors was analyzed through chi-square test. The receiver operating characteristic (ROC) curve was used to analyze the sensitivity, specificity, Youden index, and area under the curve (AUC) of lnc-MyD88 and AFP alone and in combination for the diagnosis of HCC. The relationship between MyD88 and immune infiltration was analyzed by single sample gene set enrichment analysis (ssGSEA) algorithm.

Results

Lnc-MyD88 was highly expressed in plasma samples of HCC and hepatitis B virus (HBV)-associated HCC patients. Lnc-MyD88 had better diagnostic value than AFP in HCC patients using healthy people or LC patients as control (healthy people, AUC: 0.776 vs. 0.725; LC patients, AUC: 0.753 vs. 0.727). The multivariate analysis showed that lnc-MyD88 had great diagnostic value for distinguishing HCC from LC and healthy people. Lnc-MyD88 had no correlation with AFP. Lnc-MyD88 and AFP were independent diagnostic factors for HBV-associated HCC. The AUC, sensitivity, and Youden index of the combined diagnosis of lnc-MyD88 and AFP combined were higher than those of lnc-MyD88 and AFP alone. The ROC curve of lnc-MyD88 for the diagnosis of AFP-negative HCC was plotted with a sensitivity of 80.95%, a specificity of 79.59%, and an AUC value of 0.812 using healthy people as control. The ROC curve also presented its great diagnostic value using LC patients as control (sensitivity: 76.19%, specificity: 69.05%, AUC value: 0.769). Lnc-MyD88 expression was correlated with microvascular invasion in HBV-associated HCC patients. MyD88 was positively correlated with infiltrating immune cells and immune-related genes.

Conclusion

The high expression of plasma lnc-MyD88 in HCC is distinct and could be utilized as a promising diagnostic biomarker. Lnc-MyD88 had great diagnostic value for HBV-associated HCC and AFP-negative HCC, and it had higher efficacy in combination with AFP.
Preventing stillbirth from obstructed labor: A sensorized, low-cost device to train in safer operative birth
Authors: Jaufuraully Shireen , Salvadores Fernandez Carmen , Bagchi Biswajoy , Gupta Priya , Desjardins Adrien , Siassakos Dimitrios , David Anna L. , Tiwari Manish K.
Published: January 2023

Background

98% of stillbirths occur in low- and middle- income countries. Obstructed labor is a common cause for both neonatal and maternal mortality, with a lack of skilled birth attendants one of the main reasons for the reduction in operative vaginal birth, especially in low- and middle- income countries. We introduce a low cost, sensorized, wearable device for digital vaginal examination to facilitate accurate assessment of fetal position and force applied to the fetal head, to aid training in safe operative vaginal birth.

Methods

The device consists of flexible pressure/force sensors mounted onto the fingertips of a surgical glove. Phantoms of the neonatal head were developed to replicate sutures. An Obstetrician tested the device on the phantoms by performing a mock vaginal examination at full dilatation. Data was recorded and signals interpreted. Software was developed so that the glove can be used with a simple smartphone app. A patient and public involvement panel was consulted on the glove design and functionality.

Results

The sensors achieved a 20 Newton force range and a 0.1 Newton sensitivity, leading to 100% accuracy in detecting fetal sutures, including when different degrees of molding or caput were present. They also detected sutures and force applied with a second sterile surgical glove on top. The software developed allowed a force threshold to be set, alerting the clinician when excessive force is applied. Patient and public involvement panels welcomed the device with great enthusiasm. Feedback indicated that women would accept, and prefer, clinicians to use the device if it could improve safety and reduce the number of vaginal examinations required.

Conclusion

Under phantom conditions to simulate the fetal head in labor, the novel sensorized glove can accurately determine fetal sutures and provide real-time force readings, to support safer clinical training and practice in operative birth. The glove is low cost (approximately 1 USD). Software is being developed so fetal position and force readings can be displayed on a mobile phone. Although substantial steps in clinical translation are required, the glove has the potential to support efforts to reduce the number of stillbirths and maternal deaths secondary to obstructed labor in low- and -middle income countries.
Determinants of maternal satisfaction with focused antenatal care services rendered at public health facilities in the West Shewa Zone, Central Ethiopia: A multicentre cross-sectional study
Authors: Bekele Gemechu Gelan , Seifu Benyam , Roga Ephrem Yohannes
Published: January 2023

Background

Every woman has the right to receive quality care during pregnancy. It is proven that antenatal care (ANC) reduces maternal and perinatal morbidity and mortality. The government of Ethiopia is also making intense efforts to increase the coverage of ANC. However, among pregnant women, the levels of satisfaction with the care provided are overlooked, as the percentage of women who complete all ANC visits is below 50. Therefore, this study aims to assess maternal satisfaction with ANC services rendered at public health facilities in the West Shewa Zone, Ethiopia.

Methods

A facility-based cross-sectional study was conducted among women who were receiving ANC in public health facilities in Central Ethiopia between September 1 and October 15, 2021. A total of 411 women were selected using the systematic random sampling method. The questionnaire was pretested and the data were collected electronically using CSEntry. The collected data were exported to SPSS version 26. The characteristics of the study participants were described using frequency and percentage. Bivariate and multivariate logistic regression were used to identify the factors associated with maternal satisfaction with focused ANC service.

Result

This study revealed that 46.7% [95% confidence interval (CI) (41.7%–51.6%)] of women were satisfied with ANC service. Factors such as the quality of the health institution [adjusted odd ratio (AOR) = 5.10, (95% CI: 3.33–7.75)], place of residence [AOR = 2.38, (95% CI: 1.21–4.70)], history of abortion [AOR = 0.19, (95% CI: 0.07–0.49)], and previous mode of delivery [AOR = 0.30, (95% CI: 0.15–0.60)] were significantly associated with women's satisfaction with focused ANC service.

Conclusion

More than half of pregnant women who received ANC were dissatisfied with the service they received. This should be a cause for concern, as the level of satisfaction is lower than that of the findings of previous studies conducted in Ethiopia. Institutional variables, interactions with patients, and previous experiences of pregnant women have an impact on the level of satisfaction. Due attention should be paid to primary health and communication of health professionals with pregnant women to improve the levels of satisfaction with focused ANC service.
Magnitude and associated factors of adverse perinatal outcomes among women with oligohydramnios at 3rd trimester at University of Gondar comprehensive specialized hospital, North West Ethiopia
Authors: Molla Mezigebu , Mengistu Zelalem , Tsehaye Winta , Sisay Getasew
Published: January 2023

Background

Oligohydramnios is a pregnancy condition characterized by low volume of amniotic fluid. Based on ultrasound measurement, it is defined as a single maximum vertical pocket of liquor less than 2 cm or summation of four quadrants vertical pockets of liquor measurement less than 5 cm. It is associated with multiple adverse perinatal outcomes (APO) and complicates 0.5%–5% of pregnancies.

Objective

To assess magnitude and associated factors of adverse perinatal outcome among women with oligohydramnios at 3rd trimester at University of Gondar Comprehensive Specialized Hospital, North West Ethiopia

Methods

Institution based cross-sectional study was employed from April 1 to September 30, 2021 in which 264 participants were involved. All women with oligohydramnios at 3rd trimester who meet the inclusion criteria were included. Semi- structured questionnaire was used for data collection after Pre-tested. Collected data was checked for completeness; clarity then coded and entered using Epi data version 4.6.0.2 then exported to STATA version 14.1 for analysis.

Result

The magnitude of APO was 46.6% (95%CI: 40.5–52.7%). Null parity [AOR =  2.2, 95%CI (1.2–4.2)], presence of hypertensive disorders of pregnancy (HDP) [AOR = 4.9, 95%CI (2.0–12.1)] and presence of intrauterine growth restriction (IUGR) [AOR = 8.4, 95%CI (3.5–20.2)] were found to be predictors of APO.

Conclusion

Third trimester oligohydramnios is associated with APO. The presence of HDP, IUGR and being nulliparous were predictors of APO.
Melanocortin therapies to resolve fibroblast-mediated diseases
Authors: Khodeneva Natalya , Sugimoto Michelle A. , Davan-Wetton Camilla S. A. , Montero-Melendez Trinidad
Published: January 2023

Stromal cells have emerged as central drivers in multiple and diverse diseases, and consequently, as potential new cellular targets for the development of novel therapeutic strategies. In this review we revise the main roles of fibroblasts, not only as structural cells but also as players and regulators of immune responses. Important aspects like fibroblast heterogeneity, functional specialization and cellular plasticity are also discussed as well as the implications that these aspects may have in disease and in the design of novel therapeutics. An extensive revision of the actions of fibroblasts on different conditions uncovers the existence of numerous diseases in which this cell type plays a pathogenic role, either due to an exacerbation of their 'structural' side, or a dysregulation of their 'immune side'. In both cases, opportunities for the development of innovative therapeutic approaches exist. In this regard, here we revise the existing evidence pointing at the melanocortin pathway as a potential new strategy for the treatment and management of diseases mediated by aberrantly activated fibroblasts, including scleroderma or rheumatoid arthritis. This evidence derives from studies involving models of in vitro primary fibroblasts, in vivo models of disease as well as ongoing human clinical trials. Melanocortin drugs, which are pro-resolving mediators, have shown ability to reduce collagen deposition, activation of myofibroblasts, reduction of pro-inflammatory mediators and reduced scar formation. Here we also discuss existing challenges, both in approaching fibroblasts as therapeutic targets, and in the development of novel melanocortin drug candidates, that may help advance the field and deliver new medicines for the management of diseases with high medical needs.
Inhibition of thrombin on endothelium enhances recruitment of regulatory T cells during IRI and when combined with adoptive Treg transfer, significantly protects against acute tissue injury and prolongs allograft survival
Authors: Peng Qi , Nowocin Anna , Ratnasothy Kulachelvy , Smith Richard A. , Smyth Lesley A. , Lechler Robert I. , Dorling Anthony , Lombardi Giovanna
Published: January 2023

Ischemia-reperfusion injury (IRI) amplifies T cell alloimmune responses after transplantation with thrombin playing a key pro-inflammatory role. To explore the influence of thrombin on regulatory T cell recruitment and efficacy we used a well-established model of IRI in the native murine kidney. Administration of the cytotopic thrombin inhibitor PTL060 inhibited IRI, and by skewing expression of chemokines (reducing CCL2 and CCL3 but increasing CCL17 and CCL22) increased the infiltration of M2 macrophages and Tregs. When PTL060 was combined with infusion of additional Tregs, these effects were further amplified. To test the benefits of thrombin inhibition in a transplant model, BALB/c hearts were transplanted into B6 mice with or without perfusion with PTL060 in combination with Tregs. Thrombin inhibition or Treg infusion alone led to small increments in allograft survival. However, the combined therapy led to modest graft prolongation by the same mechanisms as in renal IRI; graft survival was accompanied by increased numbers of Tregs and anti-inflammatory macrophages, and reduced expression of pro-inflammatory cytokines. While the grafts succumbed to rejection associated with the emergence of alloantibody, these data suggest that thrombin inhibition within the transplant vasculature enhances the efficacy of Treg infusion, a therapy that is currently entering the clinic to promote transplant tolerance.
Retinal structural and microvascular changes in myelin oligodendrocyte glycoprotein antibody disease and neuromyelitis optica spectrum disorder: An OCT/OCTA study
Authors: Lang Yanlin , Kwapong William Robert , Kong Lingyao , Shi Ziyan , Wang Xiaofei , Du Qin , Wu Bo , Zhou Hongyu
Published: January 2023

Purpose

To compare the optical coherence tomography (OCT)/OCT angiography (OCTA) measures in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

Methods

Twenty-one MOG, 21 NMOSD, and 22 controls were enrolled in our study. The retinal structure [retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (GCIPL)] was imaged and assessed with the OCT; OCTA was used to image the macula microvasculature [superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP)]. Clinical information such as disease duration, visual acuity, and frequency of optic neuritis and disability was recorded for all patients.

Results

Compared with NMOSD patients, MOGAD patients showed significantly reduced SVP density (P = 0.023). No significant difference (P > 0.05) was seen in the microvasculature and structure when NMOSD-ON was compared with MOG-ON. In NMOSD patients, EDSS, disease duration, reduced visual acuity, and frequency of ON significantly correlated (P < 0.05) with SVP and ICP densities; in MOGAD patients, SVP correlated with EDSS, duration, reduced visual acuity, and frequency of ON (P < 0.05), while DCP density correlated with disease duration, visual acuity, and frequency of ON.

Conclusions

Distinct structural and microvascular changes were identified in MOGAD patients compared with NMOSD patients suggesting that the pathological mechanisms are different in NMOSD and MOGAD. Retinal imaging via the SS-OCT/OCTA might have the potential to be used as a clinical tool to evaluate the clinical features associated with NMOSD and MOGAD.
Association between human leukocyte antigen and immunosuppressive treatment outcomes in Chinese patients with aplastic anemia
Authors: Chen Lingyun , Ge Meili , Huo Jiali , Ren Xiang , Shao Yingqi , Li Xingxin , Huang Jinbo , Wang Min , Nie Neng , Zhang Jing , Peng Jin , Zheng Yizhou
Published: January 2023

Background

Activated cytotoxic T cells (CTLs) recognize the auto-antigens presented on hematopoietic stem/progenitor cells (HSPCs) through class I human leukocyte antigen (HLA) molecules and play an important role in the immune pathogenesis of aplastic anemia (AA). Previous reports demonstrated that HLA was related to the disease susceptibility and response to immunosuppressive therapy (IST) in AA patients. Recent studies have indicated that specific HLA allele deletions, which helped AA patients to evade CTL-driven autoimmune responses and escape from immune surveillance, may lead to high-risk clonal evolution. Therefore, HLA genotyping has a particular predictive value for the response to IST and the risk of clonal evolution. However, there are limited studies on this topic in the Chinese population.

Methods

To explore the value of HLA genotyping in Chinese patients with AA, 95 AA patients treated with IST were retrospectively investigated.

Results

The alleles HLA-B*15:18 and HLA-C*04:01 were associated with a superior long-term response to IST (P = 0.025; P = 0.027, respectively), while the allele HLA-B*40:01 indicated an inferior result (P = 0.02). The allele HLA-A*01:01 and HLA-B*54:01 were associated with high-risk clonal evolution (P = 0.032; P = 0.01, respectively), and the former had a higher frequency in very severe AA (VSAA) patients than that in severe AA (SAA) patients (12.7% vs 0%, P = 0.02). The HLA-DQ*03:03 and HLA-DR*09:01 alleles were associated with high-risk clonal evolution and poor long-term survival in patients aged ≥40 years. Such patients may be recommended for early allogeneic hematopoietic stem cell transplantation rather than the routine IST treatment.

Conclusion

HLA genotype has crucial value in predicting the outcome of IST and long-term survival in AA patients, and thus may assist an individualized treatment strategy.
Immune responses in mildly versus critically ill COVID-19 patients
Authors: Nasrollahi Hamid , Talepoor Atefe Ghamar , Saleh Zahra , Eshkevar Vakili Mahsa , Heydarinezhad Paria , Karami Narges , Noroozi Maryam , Meri Seppo , Kalantar Kurosh
Published: January 2023

The current coronavirus pandemic (COVID-19), caused by SARS-CoV-2, has had devastating effects on the global health and economic system. The cellular and molecular mediators of both the innate and adaptive immune systems are critical in controlling SARS-CoV-2 infections. However, dysregulated inflammatory responses and imbalanced adaptive immunity may contribute to tissue destruction and pathogenesis of the disease. Important mechanisms in severe forms of COVID-19 include overproduction of inflammatory cytokines, impairment of type I IFN response, overactivation of neutrophils and macrophages, decreased frequencies of DC cells, NK cells and ILCs, complement activation, lymphopenia, Th1 and Treg hypoactivation, Th2 and Th17 hyperactivation, as well as decreased clonal diversity and dysregulated B lymphocyte function. Given the relationship between disease severity and an imbalanced immune system, scientists have been led to manipulate the immune system as a therapeutic approach. For example, anti-cytokine, cell, and IVIG therapies have received attention in the treatment of severe COVID-19. In this review, the role of immunity in the development and progression of COVID-19 is discussed, focusing on molecular and cellular aspects of the immune system in mild vs. severe forms of the disease. Moreover, some immune- based therapeutic approaches to COVID-19 are being investigated. Understanding key processes involved in the disease progression is critical in developing therapeutic agents and optimizing related strategies.
Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells
Authors: Verdier Julien , Fayet Odessa-Maud , Hemery Edouard , Truffault Frédérique , Pinzón Natalia , Demeret Sophie , Behin Anthony , Fadel Elie , Guihaire Julien , Corneau Aurélien , Blanc Catherine , Berrih-Aknin Sonia , Le Panse Rozen
Published: January 2023

Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity.
The human microbiome: A promising target for lung cancer treatment
Authors: Sun Ying , Wen Miaomiao , Liu Yue , Wang Yu , Jing Pengyu , Gu Zhongping , Jiang Tao , Wang Wenchen
Published: January 2023

Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management.
Novel method to quantify peptidylarginine deiminase activity shows distinct citrullination patterns in rheumatoid and juvenile idiopathic arthritis
Authors: Yu Karen , Dillemans Luna , Gouwy Mieke , Bessa Helena , Metzemaekers Mieke , Martens Erik , Matthys Patrick , Bossuyt Xavier , Verschueren Patrick , Wouters Carine , De Somer Lien , Proost Paul
Published: January 2023

Introduction

Peptidylarginine deiminases (PADs) mediate citrullination, an irreversible posttranslational modification that converts arginine to citrulline residues in proteins. Rheumatoid arthritis (RA) is characterized by unique autoantibodies that recognize citrullinated peptides, which are highly specific for this disease. However, the mechanism preceding the anti-citrulline response remains largely unclear. PAD enzymes are known to fuel the autoimmune response by generating autoreactive epitopes, and sustain local synovial inflammation through neutrophil extracellular trap formation. Therefore, detecting endogenous PAD activity is important to understand the pathogenesis of arthritis.

Methods

In this study, we improved a fluorescent in vitro assay to enable endogenous PAD activity characterization in complex samples. We combine the use of an in-house synthetic, arginine-rich substrate and a negatively charged dye molecule to visualize enzyme activity.

Results

This pioneering PAD assay allowed profiling of active citrullination in leukocytes and in local and systemic samples of an arthritis cohort. Our results reveal that RA and juvenile idiopathic arthritis (JIA) synovial fluids display similar levels of PAD activity. In contrast, citrullination was limited in joints of patients suffering from gout or Lyme’s disease. Interestingly, in blood, a higher level of extracellular citrullination was only found in anti-CCP-positive RA patients.

Discussion

Our finding suggests that enhanced synovial PAD activity drives the loss in tolerance towards citrullinated proteins and that systemic citrullination may indicate the risk for developing citrulline-specific autoimmunity.
Changes of natural killer cells’ phenotype in patients with chronic hepatitis B in intermittent interferon therapy
Authors: Bi Xiaoyue , Xie Si , Wu Shuling , Cao Weihua , Lin Yanjie , Yang Liu , Jiang Tingting , Deng Wen , Wang Shiyu , Liu Ruyu , Gao Yuanjiao , Shen Ge , Chang Min , Hao Hongxiao , Xu Mengjiao , Chen Xiaoxue , Hu Leiping , Lu Yao , Zhang Lu , Xie Yao , Li Minghui
Published: January 2023

Background

To investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators.

Methods

The CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry.

Results

In the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011).

Conclusion

During the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group.