bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological Presentation of Retinoblastoma in Ethiopia
Authors: Sherief Sadik Taju , Mulatu Daniel Getaneh , Wu Fran , O’Banion Jacquelyn , Dimaras Helen
Published: July 2022

Introduction: The presenting symptoms of retinoblastoma in Ethiopia, as well as their relationship to the stage of the disease, are poorly understood, but they could be important as background knowledge for creating early detection initiatives. This study aimed to describe the clinical and histopathological characteristics of retinoblastoma among Ethiopian patients. Methods: A hospital-based cross-sectional analysis of all children with newly diagnosed retinoblastoma during the study period of May 2015 to December 2019, inclusive, who presented to a tertiary referral center during were included. Demographic, clinical, and histological characteristics were collected and descriptive statistics were done using SPSS Version 20.0 software. Results: A total of 217 patients (unilateral 84.3%, bilateral 15.7%) were studied. The median age at presentation was 29 months (34 months vs. 19.5 months in unilateral and bilateral cases, respectively, p < 0.001). Among all patients, 57.8% were male. Leukocoria was the most common presenting sign (37.3%) and followed by fungating mass (31.8%). Tumors were extraocular in 40.1% of cases. From the intraocular cases, 73.3% were advanced International Intraocular Retinoblastoma Classification Group D or E disease. Sixty-two (54.4%) of the eyes had high-risk pathological features. The median lag time was significantly shorter for intraocular versus extraocular cases (5 months vs. 12 months, respectively, p < 0.001). Conclusion: Our results show that the majority of Ethiopian children with retinoblastoma have delayed presentation and late stage at diagnosis. This suggests that national health promotion campaigns to increase public knowledge on the presenting signs of retinoblastoma may be critical to achieving early diagnosis. Furthermore, the development of standard management guidelines informed by this study will be helpful in managing the complex and advanced cases currently observed.
Türkiye’de Çingenelere Yönelik Hak Temelli Politikaların Gelişimi
Authors: ŞAHYAR AKDEMİR Duru
Published: July 2022

İnsan haklarının korunması konusunda her ne kadar tek tek kişilere görev düşse de bu konuda devlet, sivil toplum örgütleri ve diğer aktörler de sorumluluk sahibidir. Devlet, insan haklarının koruyucusu konumunda olup her türden hakkın özünün gerçekleşmesinde temel bir rol oynamaktadır. Türkiye’de insan haklarına dair politikaların geliştirilmesi ve insan haklarının korunması konusunda düzenlemelerin yapılması 1990’lı yıllarda başlamıştır. Çingeneler özelinde ise bu düzenlemelerin 2000’li yıllarla birlikte hayata geçirilmeye başlandığı ifade edilebilir.

Bu doğrultuda çalışmanın amacı Çingenelere yönelik hak temelli politikaları uluslararası gelişmeleri de dikkate alarak tarihsel çerçevede ele almaktır. Çalışmada Türkiye’de gerçekleştirilen hak temelli politikalar Çingene haklarına etkileri özelinde incelenmiş ve inceleme sonuçlarına dayanarak insan haklarının korunması ve iyileştirilmesi noktasında önerilerde bulunulmuştur.
MARKA ÖZGÜNLÜĞÜNÜN MARKA AŞKI VE ALGILANAN DEĞER ÜZERİNDEKİ ETKİSİNİN İNCELENMESİ
Authors: KARAHAN Mehmet Ozan
Published: July 2022

Çalışmanın amacı, marka özgünlüğünün marka aşkı ve algılanan değer üzerindeki etkisinin belirlenmesidir. Bu kapsamda oluşturulan araştırma modelinde marka özgünlüğü unsurları (süreklilik, güvenirlik, orijinallik ve doğallık), marka aşkı ve algılanan değer değişkenleri yer almaktadır. Araştırma modelinde yer alan değişkenler arasındaki ilişkiyi keşfedilmek amacıyla, kendilerine kolayda örneklem yoluyla çevrim içi ortamda ulaşılan ve Uşak ilinde yaşayan 18 yaşından büyük toplam 318 kişi anket formlarını cevaplamıştır. Katılımcılardan elde edilen verilerin açıklayıcı faktör analizi yardımıyla geçerlilikleri ve daha sonra güvenirlikleri test edildikten sonra yapısal eşitlik modeli analizi ile de oluşturulan hipotezler test edilmiştir. Yapılan analizler sonucunda marka özgünlüğü unsurlarından süreklilik, güvenilirlik ve orijinalliğin marka aşkı ve güvenilirlik ve doğallık unsurlarının da algılanan marka değeri üzerinde anlamlı etkisinin olduğu görülmüştür. Son olarak da, algılanan değerin marka aşkı üzerinde anlamlı etkisinin olduğu gözlemlenmiştir.
Firm Size, Financial Constraints and Inverse Monotonicity of Investment-Cash Flow Sensitivity
Authors: ÇOBANOĞLU Cihan , GÜMRAH Ümit
Published: July 2022

Financial constraints hypothesis states that firms that are more likely to be financially constrained should have higher investment-cash flow sensitivity. This paper aims at testing the financial constraints hypothesis in a period when access to credit is relatively easy using firm size as a priori criterion for access to credit. We use data of firms listed on Borsa Istanbul during the period 2006–2017 and estimate regressions with panel fixed effects. We find that investment-cash flow sensitivities monotonically increase from small firms to large firms across four groups. The findings reject the financial constraints hypothesis and imply an inverse monotonic relationship between investment-cash flow sensitivities and financial constraints. We conclude that any difference in investment-cash flow sensitivities estimated by a cash flow-augmented q investment equation can’t be interpreted as an indicator of financial constraints especially when firms are not homogenous in terms of cash flow which can indicate financial distress or free cash flow problem.
YENİ YAYINCILIK MODELİ OLARAK YOUTUBE’DA DİJİTAL İÇERİKLER VE YENİLENEN İZLEME ALIŞKANLIKLARI
Authors: ÖKMEN Yunus Emre , ÇOKLUK Nil
Published: July 2022

Gündelik yaşama dijitalleşmenin hakim olmasıyla iletişim biçimleri dönüşüme uğramıştır. Bu durum yayıncılık ve anlatıcılık biçimlerini de önemli ölçüde dönüştürmüştür. Bu süreçte sosyal medya uygulamaları arasında çok sık kullanılan Youtube, geleneksel izleme ve yayın alışkanlıklarının yerini alan bir platform olarak kendini göstermektedir. Bu çalışma, iletişimin dijitalleşmesiyle değişen anlatıcılık ve yayıncılık anlayışını YouTube’un kendine özgü doğası üzerinden açıklamayı amaçlamaktadır. Çalışmanın evrenini dijital yayın platformları oluştururken, örneklem olarak YouTube seçilmiştir. Nitel araştırma yöntemlerinin ilkelerinin benimsendiği çalışmada betimsel analiz yapılmıştır. Ayrıca nitel araştırmada sıklıkla kullanılan doküman incelemesine de başvurularak, konuyla ilgili veriler toplanmıştır. Çalışmanın sonucunda YouTube’un önemli bir hikâye anlatım mecrası olduğu ve geleneksel yayıncılık anlayışının sunduğu anlatımı dönüştürdüğü öne sürülmektedir. Dolayısıyla çalışmada Youtube’un hem anlatıcı hem izleyici/dinleyici açısından yayıncılığı değiştirdiği öne sürülmektedir.
Gastronomi Blogları ve Tatma Davranışı Arasındaki İlişkilerin Analizi
Authors: AKTAŞ Ferzan , ÇETİNER Hakan , KESKİN Emrah
Published: July 2022

Sosyal medyanın hayatımıza girmesiyle birlikte aktif olarak bilgi paylaşımlarının yapıldığı, geniş kitlelere ulaşmakta aracı rol üstlenen web sayfalarının (blogların) kullanımı hızla artmıştır. Özellikle görselliğin ve tanıtım unsurlarının ön plana çıkartıldığı turizm ve gastronomi işletmeleri web sayfalarından etkin olarak yararlanmaktadır. Bireylerin gastronomi blog sayfaları aracılığıyla edinmiş oldukları bilgiler tatma davranışına olumlu etki edebilmektedir. Gastronomi bloglarının insanları etkilemeye yönelik bir çok misyonu (bilgi sunmak, rehberlik yapmak, imaj oluşturmak, siber topluluk etkisi, sosyal etki, empati yaratmak, deneyim yaşatmak) bulunmaktadır. Bu çalışmada temel olarak gastronomi bloglarının, bireylerin tatma davranışı üzerinde yarattığı etkiler incelenmiştir. Çalışma verilerinin toplanması için nicel veri toplama yöntemi olan anket tekniğinden yararlanılmıştır. Araştırma kapsamında gastronomi bloglarını takip eden 450 kişiyle iletişime geçilmiş 391 dönüt sağlanmıştır. Elde edilen bulgular SPSS Process programı kullanılarak analiz edilmiştir. İncelenen bulgulara göre gastronomi blogları ve tatma davranışı arasında pozitif yönlü ve anlamlı bir ilişki bulunmuştur.
Lipoprotein Subfractions as Markers for Predicting the Presence and Severity of Coronary Artery Disease in Patients Undergoing Coronary Angiography
Authors: Li Tingting , Zhang Yingyi , Xu Jinghan , Wang Le , Zhang Fomin , Cong Hongliang
Published: July 2022

Patients with coronary artery disease (CAD) often have normal blood cholesterol profiles that make it difficult to identify those at risk. The role of lipoprotein subfractions in the development of CAD has attracted increasing attention, and can further stratify risks. We enrolled 1578 patients undergoing coronary angiography and not taking any lipid-lowering drugs; 1033 of them were diagnosed with CAD. The severity of CAD was assessed using Gensini score (GS) and divided into 3 groups. Multivariate regression analysis showed that low-density lipoprotein particle 6 (LDL-P6) and lipoprotein (a) (Lp(a)) were independent risk factors for CAD, apart for the traditional risk factors. In receiver-operating characteristic (ROC) analysis for predicting the presence of CAD, the area under the ROC curve of traditional risk factors combined with Lp(a) and LDL-P6 for predicting CAD was .723, which was better than for traditional risk factors ( P = .023). The plasma LDL-P6 and Lp(a) concentrations in the highest tertile GS group were significantly higher than that in the lowest GS group ( P < .001). Stepwise linear regression analysis demonstrated positive correlations between Lp(a), LDL-P6 and GS ( P = .007 and P < .001). LDL-P6 and Lp(a) are useful markers for predicting the presence and severity of CAD.
Development and validation of a horse reference panel for genotype imputation
Authors: Reich Paula , Falker-Gieske Clemens , Pook Torsten , Tetens Jens
Published: July 2022

Background

Genotype imputation is a cost-effective method to generate sequence-level genotypes for a large number of animals. Its application can improve the power of genomic studies, provided that the accuracy of imputation is sufficiently high. The purpose of this study was to develop an optimal strategy for genotype imputation from genotyping array data to sequence level in German warmblood horses, and to investigate the effect of different factors on the accuracy of imputation. Publicly available whole-genome sequence data from 317 horses of 46 breeds was used to conduct the analyses.

Results

Depending on the size and composition of the reference panel, the accuracy of imputation from medium marker density (60K) to sequence level using the software Beagle 5.1 ranged from 0.64 to 0.70 for horse chromosome 3. Generally, imputation accuracy increased as the size of the reference panel increased, but if genetically distant individuals were included in the panel, the accuracy dropped. Imputation was most precise when using a reference panel of multiple but related breeds and the software Beagle 5.1, which outperformed the other two tested computer programs, Impute 5 and Minimac 4. Genome-wide imputation for this scenario resulted in a mean accuracy of 0.66. Stepwise imputation from 60K to 670K markers and subsequently to sequence level did not improve the accuracy of imputation. However, imputation from higher density (670K) was considerably more accurate (about 0.90) than from medium density. Likewise, imputation in genomic regions with a low marker coverage resulted in a reduced accuracy of imputation.

Conclusions

The accuracy of imputation in horses was influenced by the size and composition of the reference panel, the marker density of the genotyping array, and the imputation software. Genotype imputation can be used to extend the limited amount of available sequence-level data from horses in order to boost the power of downstream analyses, such as genome-wide association studies, or the detection of embryonic lethal variants.
Identification and integrated analysis of lncRNAs and miRNAs in IPEC-J2 cells provide novel insight into the regulation of the innate immune response by PDCoV infection
Authors: Jiang Shan , Chen Jianfei , Li Xiuli , Ren Weike , Li Fengxiang , Wang Ting , Li Cheng , Dong Zhimin , Tian Xiangxue , Zhang Li , Wang Lili , lu Chao , Chi Jingjing , Feng Li , Yan Minghua
Published: July 2022

Background

Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are pivotal regulators involved in the pathogenic mechanism of multiple coronaviruses. Porcine deltacoronavirus (PDCoV) has evolved multiple strategies to escape the innate immune response of host cells, but whether ncRNAs are involved in this process during PDCoV infection is still unknown.

Results

In this study, the expression profiles of miRNAs, lncRNAs and mRNAs in IPEC-J2 cells infected with PDCoV at 0, 12 and 24 hours postinfection (hpi) were identified through small RNA and RNA sequencing. The differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were screened from the comparison group of IPEC-J2 cells at 0 and 12 hpi as well as the comparison group of IPEC-J2 cells at 12 and 24 hpi. The target genes of these DEncRNAs were predicted. The bioinformatics analysis of the target genes revealed multiple significantly enriched functions and pathways. Among them, the genes that were associated with innate immunity were specifically screened. The expression of innate immunity-related ncRNAs and mRNAs was validated by RT–qPCR. Competing endogenous RNA (ceRNA) regulatory networks among innate immunity-related ncRNAs and their target mRNAs were established. Moreover, we found that the replication of PDCoV was significantly inhibited by two innate immunity-related miRNAs, ssc-miR-30c-3p and ssc-miR-374b-3p, in IPEC-J2 cells.

Conclusions

This study provides a data platform to conduct studies of the pathogenic mechanism of PDCoV from a new perspective and will be helpful for further elucidation of the functional role of ncRNAs involved in PDCoV escaping the innate immune response.
A pressure-resistant peripherally inserted central catheter is as useful as a central venous catheter for rapid fluid infusion: an in vitro study
Authors: Maki Jun , Sumie Makoto , Ide Tomoko , Nagamatsu Masako , Matsushita Katsuyuki , Shirozu Kazuhiro , Higashi Midoriko , Yamaura Ken
Published: July 2022

Background

Although peripherally inserted central catheters (PICCs) have been widely used, they have not been frequently used in anesthesia practice. The central venous pressure measured via PICCs are reportedly as accurate as that measured via central venous catheters (CVCs), but the findings concerning rapid infusion are unclear. This study examined whether or not pressure-resistant PICCs could be used for rapid fluid infusion. 

Methods

The in-line pressure was measured in similar-sized double-lumen catheters—4-Fr PICC (55, 45 and 35 cm) and 17-G CVC (20 and 13 cm)—at flow rates of saline decided using a roller pump system. We also examined the flow rate at an in-line pressure of 300 mmHg, which is the critical pressure at which hemolysis is considered to occur during blood transfusion.

Results

The pressure-resistant PICCs obtained a high flow rate similar to that of CVCs, but the in-line pressures increased in proportion to the flow rate and catheter length. Flow rates at an intra-circuit pressure of 300 mmHg were not significantly different between the 45-cm PICC and 20-cm CVC.

Conclusion

Pressure-resistant PICCs can be used for rapid fluid infusion.
Geospatial analysis as a tool to identify target areas for Chagas disease education for healthcare providers
Authors: Pacheco Gerardo J. , Fulton Lawrence , Betancourt Jose , Shanmugam Ram , Granados Paula Stigler
Published: July 2022

Chagas Disease (CD) is a neglected zoonotic disease of the Americas. It can be fatal if not diagnosed and treated in its early stages. Using geospatial and sensitivity analysis, this study focuses on understanding how to better allocate resources and educational information to areas in the United States, specifically Texas, that have the potential for increased risk of CD cases and the associated costs of addressing the disease. ICD-9 and 10 inpatient hospital diagnostic codes were used to illustrate the salience of potentially missed CD diagnoses (e.g., cardiomyopathic diagnoses) and where these are occurring with more frequency. Coding software along with GIS and Microsoft Excel 3D mapping were used to generate maps to illustrate where there may be a need for increased statewide surveillance and screening of populations at greater risk for CD. The CD cases reported to the Texas Department of State Healthcare Services (TxDSHS) are not homogenously dispersed throughout the state but rather, reveal that the incidences are in clusters and primarily in urban areas, where there is increased access to physician care, CD research and diagnostic capabilities.
Gaps in measles vaccination coverage in Kasese district, Western Uganda: results of a qualitative evaluation
Authors: Walekhwa Abel Wilson , Musoke David , Nalugya Aisha , Biribawa Claire , Nsereko Godfrey , Wafula Solomon Tsebeni , Nakazibwe Brenda , Nantongo Mary , Odera Doreen Awino , Chiara Achangwa , Boyce Ross Mathew , Mulogo Edgar Mugema
Published: July 2022

Background

Despite the availability of a highly effective vaccine, measles remains a substantial public health problem in many countries including Uganda. In this study, conducted between June–August 2020 following a local outbreak, we sought to explore the factors that could affect measles vaccination coverage in rural western Uganda.

Methods

We conducted a descriptive study using qualitative data collection approaches in the Kasese district. The research team utilized purposive sampling to identify and select participants from the public health sector and district government. We conducted key informant interviews (KII) and one focus group discussion (FGD). Responses were recorded using portable electronic devices with the FGD and KII guide installed. Interviews were conducted at the health centre and district headquarters. Data was coded and analysed using ATLAS.ti version 8 software through deductive thematic analysis to identify key themes.

Results

Barriers to measles vaccination identified in this study were premised around six themes including: (i) availability of supplies and stock management, (ii) health worker attitudes and workload, (iii) financing of vaccination outreach activities, (iv) effectiveness of duty rosters (i.e., health workers’ working schedules), (v) community beliefs, and (vi) accessibility of healthcare facilities. Respondents reported frequent vaccine supply disruptions, lack of resources to facilitate transportation of health workers to communities for outreach events, and health centre staffing that did not adequately support supplemental vaccination activities. Furthermore, community dependence on traditional medicine as a substitute for vaccines and long distances traveled by caregivers to reach a health facility were mentioned as barriers to vaccination uptake.

Conclusions

Health system barriers limiting vaccination uptake were primarily logistical in nature and reflect inadequate resourcing of immunization efforts. At the same time, local beliefs favouring traditional medicine remain a persistent cultural barrier. These findings suggest an urgent need for more efficient supply management practices and resourcing of immunization outreaches in order to achieve the Uganda Ministry of Health’s targets for childhood immunization and the prevention of disease outbreaks.
Assessing the inflammatory severity of the terminal ileum in Crohn disease using radiomics based on MRI
Authors: Ding Honglei , Li Jiaying , Jiang Kefang , Gao Chen , Lu Liangji , Zhang Huani , Chen Haibo , Gao Xuning , Zhou Kefeng , Sun Zhichao
Published: July 2022

Background

Evaluating inflammatory severity using imaging is essential for Crohn’s disease, but it is limited by potential interobserver variation and subjectivity. We compared the efficiency of magnetic resonance index of activity (MaRIA) collected by radiologists and a radiomics model in assessing the inflammatory severity of terminal ileum (TI).

Methods

121 patients were collected from two centers. Patients were divided into ulcerative group and mucosal remission group based on the TI Crohn’s disease Endoscopic Severity Index. The consistency of bowel wall thickness (BWT), relative contrast enhancement (RCE), edema, ulcer, MaRIA and features of the region of interest between radiologists were described by weighted Kappa test and intraclass correlation coefficient (ICC), and developed receiver operating curve of MaRIA. The radiomics model was established using reproducible features of logistic regression based on arterial staging of T1WI sequences. Delong test was used to compare radiomics with MaRIA.

Results

The consistency between radiologists were moderate in BWT (ICC = 0.638), fair in edema (κ = 0.541), RCE (ICC = 0.461), MaRIA (ICC = 0.579) and poor in ulcer (κ = 0.271). Radiomics model was developed by 6 reproducible features (ICC = 0.93–0.96) and equivalent to MaRIA which evaluated by the senior radiologist (0.872 vs 0.883 in training group, 0.824 vs 0.783 in validation group, P = 0.847, 0.471), both of which were significantly higher than MaRIA evaluated by junior radiologist (AUC: 0.621 in training group, 0.557 in validation group, all, P < 0.05).

Conclusion

The evaluation of inflammatory severity could be performed by radiomics objectively and reproducibly, and was comparable to MaRIA evaluated by the senior radiologist. Radiomics may be an important method to assist junior radiologists to assess the severity of inflammation objectively and accurately.
“I had so many life-changing decisions I had to make without support”: a qualitative analysis of women’s pregnant and postpartum experiences during the COVID-19 pandemic
Authors: Ashby Grayson B. , Riggan Kirsten A. , Huang Lily , Torbenson Vanessa E. , Long Margaret E. , Wick Myra J. , Allyse Megan A. , Rivera-Chiauzzi Enid Y.
Published: July 2022

Background

The COVID-19 pandemic has posed profound challenges for pregnant patients and their families. Studies conducted early in the pandemic found that pregnant individuals reported increased mental health concerns in response to pandemic-related stress. Many obstetric practices changed their healthcare delivery models, further impacting the experiences of pregnant patients. We conducted a survey study to explore the ways in which COVID-19 impacted the lives of pregnant and newly postpartum people.

Methods

A mixed-methods survey was distributed to all patients ≥18 years old who were pregnant between January 1st, 2020 – April 28, 2021 in a large Midwest health system. Open-ended survey responses were analyzed for common themes using standard qualitative methodology.

Results

Among the 1182 survey respondents, 647 women provided an open-ended response. Of these, 77% were in the postpartum period. The majority of respondents identified as white, were partnered or married, and owned their own home. Respondents reported feeling greater uncertainty, social isolation, as though they had limited social and practical support, and negative mental health effects as a result of the pandemic. Many cited sudden or arbitrary changes to their medical care as a contributing factor. Though in the minority, some respondents also reported benefits from the changes to daily life, including perceived improvements to medical care, better work-life balance, and opportunities for new perspectives.

Conclusions

This large qualitative dataset provides insight into how healthcare policy and lifestyle changes impacted pregnant and postpartum people. Respondents expressed similar levels of uncertainty and mental health concerns compared to other cohorts but less overall positivity. Our findings suggest greater attention be given to the impact of pandemic-related stress on pregnant and postpartum women. As the pandemic continues, these data identify areas where investment in additional support may have the greatest impact.
A bioinformatic analysis study of m7G regulator-mediated methylation modification patterns and tumor microenvironment infiltration in glioblastoma
Authors: Wu Xinrui , Li Chuanyu , Wang Zhisu , Zhang Yundi , Liu Shifan , Chen Siqi , Chen Shuai , Liu Wangrui , Liu Xiaoman
Published: July 2022

Background

Glioblastoma is one of the most common brain cancers in adults, and is characterized by recurrence and little curative effect. An effective treatment for glioblastoma patients remains elusive worldwide. 7-methylguanosine (m7G) is a common RNA modification, and its role in tumors has become a research hotspot.

Methods

By searching for differentially expressed genes related to m7G, we generated a prognostic signature via cluster analysis and established classification criteria of high and low risk scores. The effectiveness of classification was validated using the Non-negative matrix factorization (NMF) algorithm, and repeatedly verified using training and test groups. The dimension reduction method was used to clearly show the difference and clinical significance of the data. All analyses were performed via R (version 4.1.2).

Results

According to the signature that included four genes (TMOD2, CACNG2, PLOD3, and TMSB10), glioblastoma patients were divided into high and low risk score groups. The survival rates between the two groups were significantly different, and the predictive abilities for 1-, 3-, and 5-year survivals were effective. We further established a Nomogram model to further examine the signature,as well as other clinical factors, with remaining significant results. Our signature can act as an independent prognostic factor related to immune-related processes in glioblastoma.

Conclusions

Our research addresses the gap in knowledge in the m7G and glioblastoma research fields. The establishment of a prognostic signature and the extended analysis of the tumor microenvironment, immune correlation, and tumor mutation burden further suggest the important role of m7G in the development and development of this disease. This work will provide support for future research.
Improving anticancer effect of aPD-L1 through lowering neutrophil infiltration by PLAG in tumor implanted with MB49 mouse urothelial carcinoma
Authors: Kim Guen Tae , Kim Eun Young , Shin Su-Hyun , Lee Hyowon , Lee Se Hee , Sohn Ki-Young , Kim Jae Wha
Published: July 2022

Background

The PD-L1 antibody is an immune checkpoint inhibitor (ICI) attracting attention. The third-generation anticancer drug has been proven to be very effective due to fewer side effects and higher tumor-specific reactions than conventional anticancer drugs. However, as tumors produce additional resistance in the host immune system, the effectiveness of ICI is gradually weakening. Therefore, it is very important to develop a combination therapy that increases the anticancer effect of ICI by removing anticancer resistance factors present around the tumor.

Methods

The syngeneic model was used (n = 6) to investigate the enhanced anti-tumor effect of PD-L1 antibody with the addition of PLAG. MB49 murine urothelial cancer cells were implanted into the C57BL/6 mice subcutaneously. PLAG at different dosages (50/100 mpk) was daily administered orally for another 4 weeks with or without 5 mpk PD-L1 antibody (10F.9G2). PD-L1 antibody was delivered via IP injection once a week.

Results

The aPD-L1 monotherapy group inhibited tumor growth of 56% compared to the positive group, while the PLAG and aPD-L1 co-treatment inhibited by 89%. PLAG treatment effectively reduced neutrophils infiltrating localized in tumor and converted to a tumor microenvironment with anti-tumor effective T-cells. PLAG increased tumor infiltration of CD8 positive cytotoxic T-cell populations while effectively inhibiting the infiltration of neoplastic T-cells such as CD4/FoxP3. Eventually, neutrophil-induced tumor ICI resistance was resolved by restoring the neutrophil-to-lymphocyte ratio to the normal range. In addition, regulation of cytokine and chemokine factors that inhibit neutrophil infiltration and increase the killing activity of cytotoxic T cells was observed in the tumors of mice treated with PLAG + aPD-L1.

Conclusions

PLAG effectively turned the tumor-promoting microenvironment into a tumor-suppressing microenvironment. As a molecule that increases the anti-tumor effectiveness of aPD-L1, PLAG has the potential to be an essential and effective ICI co-therapeutic agent.
Implant survival of cemented arthroplasty following failed fixation of proximal femoral fractures in patients aged 30–60 years: a retrospective study with a median follow-up of 10 years
Authors: Yu Mingliang , Yu Minji , Zhang Yaodong , Cheng Huihui , Zeng Xianshang , Li Si , Yu Weiguang
Published: July 2022

Background

Given the unremitting growth in the volume of failed fixations of proximal femoral fractures (PFFs) in recent years, it is predictable that total hip replacements (THRs) will be the preferred surgical procedure. The long-term survival of cemented THR (CTHR) revisions remains controversial in patients aged 30–60 years. The goal of this retrospective review was to evaluate the 10-year survival of CTHRs following prior failed primary fixations of PFFs in patients aged 30–60 years.

Methods

We retrospectively identified CTHR revisions implemented at four medical centres during 2008–2017 for a failed primary fixation of PFFs in consecutive patients aged 30–60 years. The primary endpoint was implant survival calculated using the Kaplan–Meier method with 95% confidence intervals (CIs); secondary endpoints included functional scores assessed by Harris hip scores (HHS) and main revision-related orthopaedic complications. Follow-up was executed at 1, 2, 3, and 8 years following revision and then at 1-year intervals until the revision, death, or study deadline, whichever occurred first.

Results

In total, 120 patients (120 hips) who met the eligibility criteria were eligible for follow-up. The median follow-up was 10.2 years (range, 8–12 years). Kaplan–Meier survivorship showed that implant survival with revision for any reason as the endpoint was 95% at 5 years (CI: 93–97%), 89% at 8 years (CI: 86–92%), and 86% at 10 years (CI: 83–89%). Patients treated with three hollow screws had better revision-free survival than patients treated with proximal femoral nail antirotation (PFNA), dynamic hip screw (DHS) or titanium plate plus screws (three p < 0.05). Functional scores were apt to decrease gradually, and at the final follow-up, the mean HHS was 76.9 (range, 67.4–86.4). The overall rate of main revision-related orthopaedic complications was 18.3% (22/120).

Conclusion

CTHR implemented following prior failed primary fixations of PFFs tends to afford an acceptable 10-year survival, along with advantageous HHS and a low rate of main revision-related orthopaedic complications, which may support an inclination to follow the utilisation of CTHRs, especially in revision settings for intracapsular fractures.
A prognostic nomogram for stage II/III rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgical resection
Authors: Lin Yanfei
Published: July 2022

Background

The purpose of this study was to develop a large population-based nomogram incorporating the log odds of positive nodes (LODDS) for predicting the overall survival (OS) of stage II/III rectal cancer patients treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgical resection.

Methods

The Surveillance, Epidemiology, and End Results database was used to collect information on patients diagnosed with stage II/III rectal cancer between 2010 and 2015 and treated with NCRT followed by surgical resection. The Cox regression analyses were performed to determine the independent prognostic factors. In this study, LODDS was employed instead of American Joint Committee on Cancer (AJCC) 7th N stage to determine lymph node status. Then a nomogram integrating independent prognostic factors was developed to predict the 24-, 36-, and 60-month overall survival. The receiver operating characteristic (ROC) curves and calibration curves were used to validate the nomogram. Furthermore, patients were stratified into three risk groups (high-, middle-, and low-risk) based on the total points obtained from the nomogram. And Kaplan–Meier curves were plotted to compare the OS of the three groups.

Results

A total of 3829 patients were included in the study. Race, sex, age, marital status, T stage, tumor grade, tumor size, LODDS, CEA level, and postoperative chemotherapy were identified as independent prognostic factors, based on which the prognostic nomogram was developed. The area under curve values of the nomogram for the 24-, 36-, and 60-month OS in the training cohort were 0.736, 0.720, and 0.688, respectively; and 0.691, 0.696, and 0.694 in the validation cohort, respectively. In both the validation and training cohorts, the calibration curves showed a high degree of consistency between actual and nomogram-predicted survival rates. The Kaplan–Meier curves showed that the three risk groups had significant differences in overall survival (P < 0.001).

Conclusion

A large population-based nomogram incorporating LODDS was developed to assist in evaluating the prognosis of stage II/III rectal cancer patients treated with NCRT followed by surgical resection. The nomogram showed a satisfactorily discriminative and stable ability to predict the OS for those patients.
Long-term outcomes of non-metastatic breast cancer patients by molecular subtypes
Authors: Fendereski Afsaneh , Hajizadeh Ebrahim , Haghighat Shahpar , Rasekhi Aliakbar
Published: July 2022

Background

Today, with the progress of medical sciences, increasing the cure probability and survival time is an important goal of cancer treatment. This study compared long-term disease-free survival (DFS) of non-metastatic breast cancer patients based on different molecular subtypes.

Methods

This retrospective cohort study consisted of 1287 patients diagnosed with breast cancer and treated at Motamed Cancer Institute from 2000 to 2016 and followed up until 2018. Kaplan–Meier curve was fitted to data based on molecular subtypes. Then the semi-parametric mixture cure model was applied to determine the survival and cure probability of molecular subtypes by adjusting clinical and demographic factors.

Results

Among 1287 breast cancer patients, 200 (15.5%) cases died. The mean age of patients was 47.00 ± 10.72 years. Women with the HR+/HER2-subtype had the best 5-year survival rate (84.2%), whereas other subtypes had a lower rate as follows: HR+/HER2+ (77.3%), triple-negative (76.5%), and HR−/HER2+ (62.3%). Kaplan–Meier curve calculated a cure rate of about 60% and patients who survived more than 150 months were intuitively considered cured. After adjustment for clinical and demographic variables, the cure probability of HR−/Her2+ patients was substantially lower than HR+/HER2– patients (OR = 0.22), though there were no significant variations in short-term DFS based on molecular subtypes (HR = 0.91).

Conclusions

Our results confirm that the most prevalent breast cancer was HR+/HER2− tumor type which had the best prognosis. It is also concluded that HR−/HER2+ patients had the worst outcomes, with the highest rates of recurrence and metastasis and the lowest overall and disease-free survival rates.
Laparoscopic guided minilaparotomy: a modified technique for management of benign large ovarian cysts
Authors: Shaltout Mohamed F. , Maged Ahmed M. , Abdella Rana , Sediek Mona M. , Dahab Sherif , Elsherbini Moutaz M. , Elkomy Rasha O. , Zaki Sherif Sameh
Published: July 2022

Background

The aim of the study is to evaluate the efficiency and safety of a novel technique to treat large benign ovarian cysts combining benefits of laparoscopic management along with mini-laparotomy without affection of the ovarian reserve.

Methods

The study included 112 women with large benign ovarian cyst candidate for ovarian cystectomy. The technique started with laparoscopy followed by guided cyst aspiration followed by exteriorization of the ovary through minilaprotomy and completion of cystectomy through microsurgical technique. The primary outcome was ipsilateral recurrence of the cyst. Other outcomes included ovarian reserve assessment and postoperative pain.

Results

The number of women with recurrence in the ipsilateral ovary after 12, 18 and 24 months were 5 (4.5%),16 (14.3%),20 (17.85%) respectively. Assessment of ovarian reserve revealed a significant decrease in the level of serum AMH (2.82 ± 0.44 vs. 2.50 ± 0.42) and a significant increase in AFC (3.5 ± 1.7 vs. 4.9 ± 1.3) after our novel technique in surgical treatment of ovarian cysts (P value < 0.001). The operative time was 50 ± 7 and 62 ± 7 min in unilateral and bilateral cysts respectively.

Conclusions

Laparoscopic guided minilaparotomy is a safe and effective technique for the management of large benign ovarian cysts with minimal recurrence rate, ovarian reserve affection and adhesions.

Trial registration: clinical trial registry no. NCT03370952. Registered 13 December 2017,https://clinicaltrials.gov/ct2/show/NCT03370952
Construction and validation of a prognostic risk model for breast cancer based on protein expression
Authors: Huang Bo , Zhang Xujun , Cao Qingyi , Chen Jianing , Lin Chenhong , Xiang Tianxin , Zeng Ping
Published: July 2022

Breast cancer (BRCA) is the primary cause of mortality among females globally. The combination of advanced genomic analysis with proteomics characterization to construct a protein prognostic model will help to screen effective biomarkers and find new therapeutic directions. This study obtained proteomics data from The Cancer Proteome Atlas (TCPA) dataset and clinical data from The Cancer Genome Atlas (TCGA) dataset. Kaplan–Meier and Cox regression analyses were used to construct a prognostic risk model, which was consisted of 6 proteins (CASPASE7CLEAVEDD198, NFKBP65-pS536, PCADHERIN, P27, X4EBP1-pT70, and EIF4G). Based on risk curves, survival curves, receiver operating characteristic curves, and independent prognostic analysis, the protein prognostic model could be viewed as an independent factor to accurately predict the survival time of BRCA patients. We further validated that this prognostic model had good predictive performance in the GSE88770 dataset. The expression of 6 proteins was significantly associated with the overall survival of BRCA patients. The 6 proteins and encoding genes were differentially expressed in normal and primary tumor tissues and in different BRCA stages. In addition, we verified the expression of 3 differential proteins by immunohistochemistry and found that CDH3 and EIF4G1 were significantly higher in breast cancer tissues. Functional enrichment analysis indicated that the 6 genes were mainly related to the HIF-1 signaling pathway and the PI3K-AKT signaling pathway. This study suggested that the prognosis-related proteins might serve as new biomarkers for BRCA diagnosis, and that the risk model could be used to predict the prognosis of BRCA patients.
A novel 6-metabolite signature for prediction of clinical outcomes in type 2 diabetic patients undergoing percutaneous coronary intervention
Authors: Wang Xue-bin , Cui Ning-hua , Liu Xia’nan
Published: July 2022

Background

Outcome prediction tools for patients with type 2 diabetes mellitus (T2DM) undergoing percutaneous coronary intervention (PCI) are lacking. Here, we developed a machine learning-based metabolite classifier for predicting 1-year major adverse cardiovascular events (MACEs) after PCI among patients with T2DM.

Methods

Serum metabolomic profiling was performed in a nested case–control study of 108 matched pairs of patients with T2DM occurring and not occurring MACEs at 1 year after PCI, then the matched pairs were 1:1 assigned into the discovery and internal validation sets. External validation was conducted using targeted metabolite analyses in an independent prospective cohort of 301 patients with T2DM receiving PCI. The function of candidate metabolites was explored in high glucose-cultured human aortic smooth muscle cells (HASMCs).

Results

Overall, serum metabolome profiles differed between diabetic patients with and without 1-year MACEs after PCI. Through VSURF, a machine learning approach for feature selection, we identified the 6 most important metabolic predictors, which mainly targeted the nicotinamide adenine dinucleotide (NAD+) metabolism. The 6-metabolite model based on random forest and XGBoost algorithms yielded an area under the curve (AUC) of ≥ 0.90 for predicting MACEs in both discovery and internal validation sets. External validation of the 6-metabolite classifier also showed good accuracy in predicting MACEs (AUC 0.94, 95% CI 0.91–0.97) and target lesion failure (AUC 0.89, 95% CI 0.83–0.95). In vitro, there were significant impacts of altering NAD+ biosynthesis on bioenergetic profiles, inflammation and proliferation of HASMCs.

Conclusion

The 6-metabolite model may help for noninvasive prediction of 1-year MACEs following PCI among patients with T2DM.
Modified jaw thrust I-gel insertion technique in adults: a case series
Authors: Kumar Dileep
Published: July 2022

Background

The I-gel is a second-generation supraglottic airway device that is built with a noninflatable elliptical gel material cuff and has a wide semirigid stem. The I-gel supralaryngeal seal has shown promising efficacy for both spontaneous and controlled ventilation under general anesthesia. The recommended, standard I-gel insertion technique is relatively challenging due to its shape and cuff size. Usually, the I-gel becomes entrapped at the oral cavity and requires excessive force to negotiate across the oropharynx, resulting in insertion resistance, tongue obstruction, insertion failure, and intraoral trauma. This case series evaluated a modified jaw thrust I-gel insertion technique because it is claimed to allow smooth and atraumatic I-gel placement in adults.

Case presentation

In this case series, ten male and female Indo-Aryan group of Asian patients aged 18–60 years were recruited for I-gel device placement through a modified jaw thrust technique for short to intermediate surgical duration in below-umbilical surgical procedures. Patient consent was obtained, and baseline vital signs such as electrocardiogram, noninvasive blood pressure, and peripheral oxygen saturation readings were recorded. Following preoxygenation, propofol 2 mg/kg was administered for anesthesia induction and nalbuphine 0.1 mg/kg for analgesia. In all patients, an I-gel was placed by the modified jaw thrust technique. The patient’s demographics, number of attempts, I-gel insertion resistance, and insertion time duration were recorded.

Conclusion

The findings showed a 100% first-attempt insertion rate along with negligible insertion resistance and convincing insertion time duration with modified jaw thrust I-gel insertion technique. However, a blood-stained I-gel was observed in one male patient at the time of removal. The patient’s demographics such as age, weight, American Society of Anesthesiologists status, and surgical and anesthesia duration were found not to be significant. The modified jaw thrust I-gel insertion technique could be considered as an alternative in adults when difficulty is encountered with the standard I-gel insertion technique.
Modulation of synaptic plasticity, motor unit physiology, and TDP-43 pathology by CHCHD10
Authors: Liu Tian , Woo Jung-A. A. , Bukhari Mohammed Zaheen , Wang Xinming , Yan Yan , Buosi Sara Cazzaro , Ermekbaeva Aizara , Sista Apoorva , Kotsiviras Peter , LePochat Patrick , Chacko Ann , Zhao Xingyu , Kang David E.
Published: July 2022

Mutations in CHCHD10, a gene coding for a mitochondrial intermembrane space protein, are associated with Frontotemporal dementia (FTD)-Amyotrophic lateral sclerosis (ALS) spectrum disorders, which are pathologically characterized by cytoplasmic inclusions containing TDP-43. FTD/ALS-linked CHCHD10 mutations and TDP-43 inclusions similarly induce mitochondrial defects in respiration, fusion/fission, mtDNA stability, and cristae structure, while sizeable amounts of cytoplasmic TDP-43 aggregates are found in mitochondria. However, the mechanistic link between CHCHD10 and TDP-43 pathogenesis remains unclear. In this study, we present immunohistochemical and biochemical evidence demonstrating that insoluble CHCHD10 aggregates accumulate and colocalize with phospho-TDP-43 inclusions in brains of FTLD-TDP and AD patients, and that insoluble CHCHD10 levels tightly correlate with insoluble TDP-43 levels in control and FTLD-TDP brains. In an experimental exploration of this pathological phenotype, transgenic mice neuronally expressing FTD/ALS-linked CHCHD10R15L or CHCHDS59L mutations but not CHCHD10WT transgenic mice exhibit significantly increased CHCHD10 aggregation and phospho-TDP-43 pathology, which often colocalize within the same inclusions. Such pathologies are reflected in poor functional outcomes in long-term synaptic plasticity, motor unit physiology, and behavior in CHCHD10R15L and CHCHDS59L transgenic mice. In contrast, expression of CHCHD10WT in hTDP-43 transgenic mice (TAR4;CHCHD10WT) significantly mitigates phospho-TDP-43 pathology and rescues TDP-43-induced impairments in synaptic integrity and long-term synaptic plasticity. In isolated mitochondria, the S59L mutation induces the aggregation of resident CHCHD10S59L protein as well as the aggregation and slower turnover of recombinant TDP-43 imported into mitochondria. Likewise, in an in vitro cell-free system, the S59L mutation induces the aggregation of CHCHD10S59L protein while simultaneously enhancing the aggregation of recombinant TDP-43, as evidenced by filter trap assays and atomic force microscopy. In contrast, recombinant CHCHD10WT inhibits the growth of TDP-43 aggregates. These results in human brains, transgenic mice, and in vitro systems substantiate the role of wild type and mutant CHCHD10 in modulating mitochondrial CHCHD10 and TDP-43 pathogenesis together with associated phenotypes in long-term synaptic plasticity and motor unit physiology in mice and humans.
Socio-economic and socio-demographic determinants of diet diversity among rural pregnant women from Pune, India
Authors: Gokhale Devaki , Rao Shobha
Published: July 2022

Background

Diet diversity signifies the nutrient adequacy of an individual and thus has gained widespread significance in recent times. In developing countries achieving maximum diet diversity, especially among pregnant women from rural areas is challenging although of great importance. However, to do so understanding the primary factors associated with diet diversity is important. This paper, therefore, assessed the socio-demographic and socio-economic determinants of diet diversity among rural pregnant women in India.

Methods

The study consisted of a community-based prospective cohort of n = 204 pregnant women attending primary healthcare centers (PHC) across 14 villages in Mulshi Taluka, Pune, Maharashtra, India. The data was collected using a structured questionnaire through a one-to-one interview method.

Results

The prevalence of low, medium and high diet diversity was 56.4%, 33.3%, and 10.3% respectively. Minimum diversity in the diet was achieved among 73.5% of pregnant women. The mean diet diversity score (DDS) was 3.6 ± 1.3 with starchy staples being (100%) of commonly consumed foods. Young (< 20 years) women (OR = 5.2; CI:1.9- 13.8), housewives (OR = 3; CI:1.4–6.7), husbands working as skilled laborers (OR = 2.5; CI:1.2–5.5) were at significant risk of having low diet diversity scores. Whereas, those living in a joint family (OR = 0.3; CI:0.1–0.6), not owning a house (OR = 0.5; CI:0.2–0.9), and having a poor income (OR = 1.9; CI: 0.9- 3.7) were less likely to have low diet diversity.

Conclusion

Socio-economic and demographic factors (maternal age, mother's occupation, and husband's occupation) influenced the diet diversity among pregnant women. Monotonous diets are commonly seen in developing countries, especially in rural areas which can be a risk factor for poor nutrient adequacy and health of pregnant women. Policies and programs about these determinants of diet diversity should be enacted to replace the poor quality diets to ensure improved diet diversity and nutrient adequacy.