bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction with Precision: Does TAILORx Make Chemotherapy a Personalised Treatment?
Authors: Tonarelli Lorena
Published: December 2022

Adjuvant chemotherapy (CT) is commonly recommended to breast cancer patients following surgery. However, not all patients benefit from it, and the intervention is associated with a substantial clinical burden, which also negatively affects quality of life. The aim of this symposium was to provide insights into the use of the 21-gene Oncotype DX® Breast Recurrence Score (RS) assay (Genomic Health Inc., Redwood City, California, USA) to optimise treatment decisions. The symposium started with an overview of the role of biomarkers in precision medicine in early breast cancer, provided by Prof Sparano, with a focus on recent developments in predicting CT benefit and assisting with the treatment decision-making based on the Oncotype DX® assay. CT is becoming a personalised medicine, comparable with oestrogen receptor (ER) expression testing and hormonal therapy, or human epidermal growth factor receptor (HER)2 testing and trastuzumab. Prof Sparano, the principal investigator of the TAILORx study, presented clinical trial and real-world evidence demonstrating a lack of CT benefit in approximately 80% of patients (those with RS results 0–25) and a substantial benefit in about 20% of patients (mainly those with RS results 26–100). This was brought into the perspective of clinical practice by Prof Penault-Llorca, who discussed the value of genomic assays versus classical pathological parameters and predictors of prognosis (e.g., age, ER and HER2 status, histological subtypes, Ki67 +/- mitotic index) and their associated risk of CT overtreatment and undertreatment. Prof Penault-Llorca also provided an insight into the lack of interchangeability of currently available genomic breast cancer tests. The symposium concluded with a presentation by Prof Nitz on CT decisions, specifically in node-positive breast cancer patients. Clinical and real-world data from large registries support CT decisions based on RS, independent of nodal status, to prevent overtreatment in daily routine.
Spor Müsabakalarında Görev Yapan Hakemlerin Ceza Sorumluluğu
Authors: ÖZOCAK Gürkan
Published: December 2022

Spor faaliyetlerine katılan sporcu, antrenör, yönetici gibi spor süjelerinin fiilleri, ilgili federasyonun talimatlarına aykırı olabileceği gibi, bu fiiller bir ceza normunu ihlal ettiklerinde bu kişilerin ceza sorumlulukları da ortaya çıkabilmektedir. Bu spor süjelerinin en önemlilerinden birisi de hakemlerdir. Özellikle spor müsabakasını yönetme görevini üstlenen ve oyun üzerinde tam hâkimiyete sahip olan hakemlerin ceza sorumluluğunun ayrıca ele alınması son derece önemlidir. Hakemlerin spor müsabakaları esnasında veya spor faaliyetiyle ilgili işleyebilecekleri kasten veya taksirle yaralama, mala zarar verme, hakaret, tehdit, şike ve teşvik primi gibi birçok suçtan bahsedilebilir. Bununla beraber, hangi suç olursa olsun, Türk hukukundaki düzenlemeler uyarınca, hakemler işlemiş oldukları fiiller bakımından “kamu görevlisi” sayılmakta ve ceza sorumlulukları buna göre belirlenmektedir.
Nöroteknoloji ve Bilişsel Özgürlük
Authors: KARASULU Zeynep
Published: December 2022

Nöroteknoloji alanında son yıllarda yaşanan büyük gelişmeler, insan beynindeki verilere erişme, bu verileri toplama ve işleme konusunda önemli olanaklar sunmaktadır. Özellikle fonksiyonel manyetik rezonans tekniği gibi beyin görüntüleme tekniklerinin kullanımıyla, insan beynine herhangi bir müdahalede bulunmaksızın beyin aktivitelerinin görüntülenmesi ve kaydedilmesi mümkün hale gelmiştir. Günümüzde, beyin görüntüleme tekniklerinin, kişilerin düşünce ve tutumları hakkında bilgi edinmenin yanında, klinik amaçlarla kullanımı da son derece yaygındır. Bununla birlikte, nöroteknolojinin kullanımı, kişilerin davranışlarında istenmeyen değişikliklere ve mental zararlara yol açarak, temel hak ve özgürlüklerine yönelik tehdit yaratma potansiyeli taşımaktadır. Özellikle ABD’de ortaya çıkan nöro-pazarlama ve nöro-reklamcılık gibi sektörlerin, kişilerin tercihlerinin yönlendirilmesi gibi ticari amaçlarla nöroteknolojik yöntemleri kullanması buna örnek olarak gösterilebilir.
Bu çerçevede, bu çalışmada, öncelikle nöroteknoloji ve insan hakları arasındaki ilişki ortaya konulmaya çalışılmakta ve halihazırdaki hakların, nöroteknoloji alanındaki gelişmelere yanıt vermek bakımından yeterli olmayabileceğinden hareketle, son yıllarda tartışılmaya başlanan bilişsel özgürlük kavramı ile Lenca ve Andorno’nun “nöro-haklar” adı altında öne sürdüğü, “mental gizlilik hakkı”, “mental bütünlük hakkı” ve “psikolojik devamlılık hakkı” tartışılmaktadır.
IMPLEMENTASI WALK IN CUSTOMER (WIC) DAN ENHANCED DUE DILIGENCE KEPADA NASABAH SEBAGAI PENCEGAHAN MONEY LAUNDERING PT. BANK SUMUT KCP SYARIAH H.M YAMIN
Authors: Himmah Mufidatul , Hidayatullah Mohammad Alief , Fatimah Siti
Published: December 2022

Banking institutions are institutions that are often used by the public to carry out financial transactions, whether in the form of savings, transfers, investments and others. In this case, Islamic Banking carries out funding and lending activities by promoting various types of financial transaction services, becoming the main center in crime. money laundering and terrorism financing to hide illegal money. Therefore, the OJK has made regulations regarding the prevention of Money Laundering and the financing of Terrorism which includes CDD and EDD PT. Bank Sumut Syariah KCP H.M Yamin has implemented Customer Due Diligence on Walk In Customer (WIC) and Enhanced Due Diligence on Customers as an effort to prevent money laundering and terrorism financing. In this journal research using qualitative methods with a descriptive approach. the data taken is by interview and observation techniques. Observations indicate that the implementation of WIC on Customer Due Diligence is carried out when the Bank doubts customer information by conducting identification and verification. In addition, at WIC where previously WIC did not need to report to Customer Service when making transactions and went directly to the teller. However, for now there has been a circular letter of change from the Head Office of Bank Sumut Syariah regarding the implementation of WIC where WIC is required to report to Customer service first after obtaining approval from CS, then WIC can go directly to the teller. The implementation of Enhanced Due Diligence is carried out for Politically Exposed Person customers. But in practice at PT. Bank Sumut Syariah KCP H.M Yamin is carried out if there are suspicious transactions or when there are cases.
Hadislerin Kabul ve Reddinde İcmâın Rolü
Authors: Yılmazlar Esma , Köktaş Yavuz
Published: December 2022

Teorik anlamda “ümmetin hata üzerinde birleşmeyeceği” prensibine dayanan icmâ, Kur’ân’ın sonraki nesillere aktarılması ve mushaf haline getirilmesi; sünnetten olanın ve olmayanın tespiti gibi konuların da temel dayanağını oluşturur. Bu yüzden İslâmî ilimlerin hemen hepsinde epistemik bir değere sahiptir. Bu çalışma, fıkıh ve hadis ilminde yer alan icmâın, rivâyetlerin kabul ve reddindeki işlevini konu edinmektedir. Rivâyetlerin icmâa uygun olması gerektiği tartışmaları, hicrî ikinci asırdan itibaren itikâdî ve fıkhî ekollerin gündeminde olan bir husustur. Fakîhler, haber-i vâhidlerin sübutu ve delaletini zannî gördükleri için haber teorilerinde icmâın katʿîliğinden faydanmışlardır. Muhaddisler ise klasik hadis usûlündeki isnad ve rical tenkid kriterlerine göre hüküm verdikleri hadisleri tenkid, teʾvîl ve izahlarında icmâa rol vermişlerdir. Bu araştırmayla icmâın hicrî ikinci asırdan itibaren rivayetlerin değerlendirilmesinde nasıl bir metoda konu olduğu ve kullanılan icmâın mahiyetinin anlaşılmasına katkı sunmak amaçlanmaktadır. Böylece icmâın iddia edildiği gibi muhaddislerin metin tenkidi yöntemlerinden biri olmadığı sonucuna ulaşılacaktır.
Implementation of Regional PEN Loans and Their Impact on The Absorption of Labor in The Regions
Authors: Sofi Irfan , Sakti Moza Pandawa , Bachtiar Arioma , Nugraha Septian P.
Published: December 2022

The Covid-19 pandemic has reduced regional income, thus impacting the implementation of several planned activities in 2020. The Central Government provides funding assistance in the form of Regional Loans for National Economic Recovery. The purpose of this articel is to determine the impact of 2020 Regional National Export Development Loans on Economic Recovery in the Regions, especially on employment. This study uses a combination method. The results of the study found that the 2020 Regional National Export Development Loan had a positive impact on regional economic recovery. Support for the increase in the average capital expenditure which fell by 2.33 times greater for the regions, projects financed from regional PEN loans have maximized the use of local labor to reduce unemployment due to the Covid-19 Pandemic.
CARACTERÍSTICAS DO PROCESSO DE MUNICIPALIZAÇÃO DO ENSINO FUNDAMENTAL I NO ESTADO DE SÃO PAULO
Authors: Esposito Ícaro Rodrigo , Nascente Renata Maria  Moschen
Published: December 2022

O objetivo deste texto é analisar o processo de municipalização do Ensino Fundamental I, no estado de São Paulo, por meio de artigos acadêmicos entre 1996 e 2019. A análise indica que a municipalização do Ensino Fundamental I foi intensa em seus primeiros anos, com a contínua adesão de algumas prefeituras, em função do recebimento de verbas condicionadas à oferta de vagas. Além disso, foi possível compreender que esse processo pode ter contribuído para a universalização do acesso à educação. Por outro lado, pode ter aumentado a precarização da oferta de educação básica de qualidade social, além de ter sido pseudo-descentralizador e pseudo-participativo. Um aspecto positivo foi a criação de secretarias, conselhos, planos e estatutos municipais de educação.
Contando histórias com o jogo teatral e a audiodescrição
Authors: Cerejeira Thiago de Lima Torreão , Alves Jefferson Fernandes
Published: December 2022

A articulação de duas oficinas realizadas em um curso de extensão entre participantes com e sem deficiência visual oportunizou a experimentação de processos criativos e artísticos envolvendo a contação de histórias e a audiodescrição por meio dos jogos teatrais. A análise do processo permitiu vislumbrar potentes caminhos que consideram a força e o uso da palavra poética presente na contação de histórias. Tal aspecto instaura o desafio de repensar as formas de fazer audiodescrição como recurso de acessibilidade comunicacional que auxilia na compreensão da pessoa com deficiência visual afim de que incorporem novas possibilidades e privilegiem um estado de vocalidade que deve acompanhar a poeticidade do espetáculo teatral ou da obra artística.
PROPOSTA DE MODELOS EXPERIMENTAIS CONSTRUÍDOS COM MATERIAIS DE BAIXO CUSTO PARA O ENSINO DE CIÊNCIAS EM TEMAS DE ASTRONOMIA
Authors: Rodrigues Clóves Gonçalves , Borges Cindy Lisiani Sales
Published: December 2022

Este artigo é voltado para a prática docente, onde são apresentados alguns experimentos didáticos de fácil acesso e baixo custo, os quais simulam fenômenos astronômicos elementares que podem ser utilizados por professores de ciências do ensino médio e fundamental, trabalhando com a criatividade e visualização tridimensional de modelos para o ensino desta ciência tão primordial e presente em nosso dia-a-dia.
Editorial Vol. 10, no 3
Authors: Poletto Fabio Guilherme , de Almeida Ribeiro Felipe
Published: December 2022

Editorial Vol. 10, no. 3
Effect of support on the performance of PtRu-based catalysts in oxidative steam reforming of ethanol to produce hydrogen
Authors: Tang Chih-Wei , Liu Chiu-Hung , Yu Shen-Wei , Wang Chen-Bin
Published: December 2022

Oxidative steam reforming of ethanol (OSRE) to produce hydrogen has been investigated over a series of supported PtRu catalysts, with different supports. Bimetallic PtRu-based catalysts were prepared by the impregnation method using H2PtCl6 and RuCl3 as precursors. Six supports (reducible oxides of ZrO2, CeO2, and Co3O4, and irreducible oxides of ZnO, Al2O3, and NiO) were chosen to fabricate bimetallic catalysts. The catalytic performance of the OSRE reaction in the series of PtRu-based samples was evaluated using a fixed-bed flow reactor under atmospheric pressure. In front reaction, the catalyst was pre-activated by reduction under 200°C for 3 h. The gas hourly space velocity was adjusted at 66,000 h−1, and the optimal molar ratios of the H2O/EtOH and O2/EtOH feeds were 4.9 and 0.44, respectively. The results indicated that the PtRu supported on the ZrO2 and CeO2 exhibited superior catalytic performance in the OSRE reaction under a low temperature (a TR of approximately 320°C) for producing the main products of H2 and CO2 with lower CO and CH4 by-products. Also, it was quite stable during a long time evaluation; the maximum YH2 maintained at 4.5–4.2, and the CO distribution approached 3.3–3.5 mol% around 84 h test at 340°C over the PtRu/ZrO2 catalyst.
Model structure and ensemble size: Implications for predictions of groundwater age
Authors: Kitlasten Wesley , Moore Catherine R. , Hemmings Brioch
Published: December 2022

This paper examines the influence of simplified vertical discretization using 50- to four- layer models and ensemble size on history matching and predictions of groundwater age for a national scale model of New Zealand (approximately 265,000 km2). A reproducible workflow using a combination of opensource tools and custom python scripts is used to generate three models that use the same model domain and underlying data with only the vertical discretization changing between the models. The iterative ensemble smoother approach is used for history matching each model to the same synthetic dataset. The results show that: 1) the ensemble based mean objective function is not a good indicator of model predictive ability, 2) predictive failure from model structural errors in the simplified models are compounded by history matching, especially when small (<100 member) ensembles are used, 3) predictive failure rates increase with iteration, 4) predictive failure rates for the simplified model reach 30–65% using 50-member ensembles, but stabilize at relatively low values (<10%) using the 300 member ensemble, 5) small (50 member) ensembles contribute to predictive failure of 22–30% after six iterations even in structurally “perfect” models, 6) correlation-based localization methods can help reduce prediction failure associated with small ensembles by up to 45%, 7) the deleterious effects of model simplification and ensemble size are problem specific. Systematic investigation of these issues is an important part of the model design, and this investigation process benefits greatly from a scripted, reproducible workflow using flexible, opensource tools.
Informal vocational training and sustainable livelihood skills among unemployed youth in low-income countries: Insights from a SWOT analysis of tailoring apprenticeships in Cameroon
Authors: Ngyah-Etchutambe Ijang Bih , Aki Etta Mercy , Mbi Suzan Ebai , Farinkia Ndang Gilbert
Published: December 2022

Introduction

Many low-income countries have very high levels of youth unemployment. Self-employment provides one path to economic independence for these youths, but to be successful, they require both technical and entrepreneurial skills. Most youth employment interventions and research have focused on the formal education sector, which has limited the understanding of the role of education in reducing youth unemployment. The role of informal learning opportunities offered by small businesses and micro-enterprises, which constitute one of the largest sectors of the economy in many low-income countries, has been undermined. This study examines the potential of such learning opportunities through a case study of informal apprenticeships in tailoring in Cameroon, Central Africa.

Methods

A Strengths, Weaknesses, Opportunities, and Threats analysis drew on the perspectives of both informal trainers (n  = 42; 88% women) and apprentices (n  = 16; mean age: 22 years; 69% women) in small-tailoring enterprises in the city of Buea. Qualitative data from semi-structured interviews was subjected to a thematic analysis.

Results and discussion

The perceived strengths of informal apprenticeships included developing suitable work strategies, attitudes, technical and entrepreneurial skills in unemployed youth through practice and collaboration with other apprentices. However, participants also identified several weaknesses in informal training, including inadequate access to specialized machines and limitations on training imposed by the poor literacy skills of some apprentices. Most respondents perceived that tailoring provided an opportunity for a lucrative career while meeting their community’s need for appropriate clothing. However, high taxes and constant power failures were identified as threats to the continuing viability of local tailoring. Trainers also noted that few youths were interested in learning the trade. Taken together, the results indicate that the potential for informal vocational training to nurture youths toward developing their own enterprise would be strengthened if training included basic literacy skills, building self-confidence, strategies to raise and manage capital and the production of attractive designs to match their competition.
The relationship between uric acid and total femur bone mineral density in hypertensive and non-hypertensive populations
Authors: Su Yingjie , Ding Ning , Zhou Yang , Yang Guifang , Chai Xiangping
Published: December 2022

Objective

This study aimed to explore the association between uric acid (UA) and total femur bone mineral density (BMD) in hypertensive and non-hypertensive groups.

Methods

We conducted a cross-sectional study of 13,108 participants in the NHANES database, including 4,679 hypertensive and 8,429 non-hypertensive subjects. A weighted multiple linear regression analysis was conducted to explore the association between UA and total femur BMD.

Results

In the hypertensive group, the relationship between UA and total femur BMD was positive [β, 3.02 (95% CI, -0.44 to 6.48), p = 0.0962). In the non-hypertensive group, the association was significantly positive [β, 5.64 (95% CI, 2.06–9.22), p = 0.0038]. In gender-stratified analysis, UA was analyzed as a continuous variable and a categorical variable (quartile). The significantly positive association was present in both the hypertensive male group [β, 5.10 (95% CI, 0.98–9.21), p for trend = 0.0042] and non-hypertensive male group [β, 10.63 (95% CI, 6.32–14.94), p for trend = 0.0001]. A smooth curve fitting showed that in the hypertensive male group, the relationship between UA and total femur BMD was an inverted U-shaped curve. In the hypertensive female group, the relationship was basically negative. In the non-hypertensive population, the relationship between UA and total femur BMD was an inverted U curve in both men and women.

Conclusion

In the hypertensive male group, the association between UA and total femur BMD was an inverted U-shaped curve. As to women, the relationship was basically negative. In the non-hypertensive group, the association between UA and total femur BMD was an inverted U-shaped curve in different genders.
Osteocalcin is associated with triglyceride glucose index rather than HOMA-IR in men with type 2 diabetes
Authors: Huang Huijie , Wang Ai , Cong Li , Zeng Yingjuan
Published: December 2022

Introduction

The involvement of osteocalcin in the regulation of glucose tolerance in humans is controversial. We utilized a novel and practical insulin resistance surrogate, the triglyceride-glucose (TyG) index, to investigate the association between serum osteocalcin and insulin resistance in men with type 2 diabetes (T2D).

Methods

This was a retrospective cross-sectional study that included 667 male patients suffering from T2D, with measurements of N-terminal mid-fragment of osteocalcin (N-MID), triglycerides (TG), fasting blood glucose (FBG) and C-peptide collected on the same day. We used the TyG index and HOMA-IR as surrogate measures for insulin resistance. Binary logistic regression models that adjust the sociodemographic characteristics and metabolism-related factors were used to assess the associations between osteocalcin and insulin resistance. Restricted cubic spline (RCS) analysis was used to test the potential non-linear relationship between N-MID and the risk of severe insulin resistance. Subgroup analysis evaluated the robustness of the association.

Results

N-MID was correlated with the level of insulin resistance when quantified by the TyG index in unadjusted and adjusted binary logistic regression models (all p < 0.05), but the relationship was not observed when assessed by HOMA-IR (all p > 0.05). RCS model further confirmed that the association between N-MID and the severe insulin resistance measured by the TyG index was non-linear (P = 0.047). Subgroup analysis showed that the association was detected only in younger patients with lower BMI and poorer glycemic control, without hypertension or smoking.

Conclusions

Osteocalcin was inversely associated with the TyG index in men with T2D.
Circulating brain-derived extracellular vesicles expressing neuroinflammatory markers are associated with HIV-related neurocognitive impairment
Authors: de Menezes Erika G. Marques , Liu Jocelyn S. , Bowler Scott A. , Giron Leila B. , D’Antoni Michelle L. , Shikuma Cecilia M. , Abdel-Mohsen Mohamed , Ndhlovu Lishomwa C. , Norris Philip J.
Published: December 2022

Background

Neurocognitive impairment remains prevalent in people with HIV (PWH) despite long term virological suppression by antiretroviral therapy (ART) regimens. Systemic and neuro-inflammatory processes are suggested to contribute to the complex pathology leading to cognitive impairment in this population, yet the underlying mechanisms remain unresolved. Extracellular vesicles (EVs) play a central role in intracellular communication and have emerged as key modulators of immunological and inflammatory responses. In this report, we examined the impact of EVs in PWH experiencing cognitive deficits to determine their relevance in HIV associated neuropathology.

Methods

EV phenotypes were measured in plasma samples from 108 PWH with either cognitive impairment (CI, n=92) or normal cognition (NC, n=16) by flow cytometry. Matched cerebrospinal fluid (CSF)-derived EVs were similarly profiled from a subgroup of 84 individuals who underwent a lumbar puncture. Peripheral blood mononuclear cells were assayed by flow cytometry to measure monocyte frequencies in a subset of 32 individuals.

Results

Plasma-EVs expressing CD14, CD16, CD192, C195, and GFAP were significantly higher in HIV-infected individuals with cognitive impairment compared to individuals with normal cognition. Increased CSF-EVs expressing GFAP and CD200 were found in the cognitive impairment group compared to the normal cognition group. Frequencies of patrolling monocytes correlated with plasma-EVs expressing CD14, CD66b, MCSF, MAP2, and GFAP. Frequencies of CD195 expression on monocytes correlated positively with plasma-EVs expressing CD41a, CD62P, and CD63. Expression of CD163 on monocytes correlated positively with CSF-EVs expressing GFAP and CD200. Finally, the expression of CD192 on total monocytes correlated with CSF-EVs expressing CD200, CD62P, and CD63.

Conclusions

EVs expressing monocyte activation and neuronal markers associated with HIV associated cognitive impairment, suggesting that distinct EV subsets may serve as novel biomarkers of neuronal injury in HIV infection. Further circulating platelet EV levels were linked to monocyte activation indicating a potential novel interaction in the pathogenesis of HIV-related cognitive impairment.
Can vitamin D status influence seroconversion to SARS-COV2 vaccines?
Authors: Shahini Endrit , Pesce Francesco , Argentiero Antonella , Solimando Antonio Giovanni
Published: December 2022

Existing data indicate an association between vitamin D deficiency and increased severity of respiratory distress due to COVID-19 infection, especially in high-risk populations. To date, the effect of vitamin D on immunogenicity to SARS-CoV-2 vaccines has been investigated solely in young healthcare workers in a few studies, yielding conflicting findings, yet highlighting that the response to immunization is inversely related to age. Vitamin D status can potentially influence the antibody titers in people with a previous (or naïve) SARS-CoV-2 infection and vaccination, given its role in immune regulatory functions. From this standpoint, vitamin D supplementation can help reduce the risk of SARS-CoV-2 infection, COVID-19 severity/mortality and rebalance immunological function, particularly in subjects with vigorous T lymphocyte responses to COVID-19. However, more research is needed to establish a correlation between vitamin D status and the generation of protective serological responses to SARS-CoV-2 vaccination.
The role of lncRNAs in the tumor microenvironment and immunotherapy of melanoma
Authors: Zhou Wencheng , Xu Xuewen , Cen Ying , Chen Junjie
Published: December 2022

Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs closely related to the occurrence and development of melanoma. We summarize the role of lncRNAs in the immune microenvironment, immunotherapy and targeted therapy to provide new targets and therapeutic methods for clinical treatment.
Early calcineurin-inhibitor to belatacept conversion in steroid-free kidney transplant recipients
Authors: Tawhari Ibrahim , Hallak Patrick , Bin Sofia , Yamani Fatmah , Safar-Boueri Maria , Irshad Aazib , Leventhal Joseph , Ansari Mohammed Javeed , Cravedi Paolo , Gallon Lorenzo
Published: December 2022

Background

Belatacept (Bela) was developed to reduce nephrotoxicity and cardiovascular risk that are associated with the chronic use of Calcineurin inhibitors (CNIs) in kidney transplant recipients. The use of Bela with early steroid withdrawal (ESW) and simultaneous CNI avoidance has not been formally evaluated.

Methods

At 3 months post-transplant, stable kidney transplant recipients with ESW on Tacrolimus (Tac) + mycophenolate (MPA) were randomized 1:1:1 to: 1) Bela+MPA, 2) Bela+low-dose Tac (trough goal <5 ng/mL), or 3) continue Tac+MPA. All patients underwent surveillance graft biopsies at enrollment and then at 12, and 24 months post-transplant. Twenty-seven recipients were included; 9 underwent conversion to Bela+MPA, 8 to Bela+low-dose Tac and 10 continued Tac+MPA. Serial blood samples were collected for immune phenotyping and gene expression analyses.

Results

The Bela+MPA arm was closed early due to high rate of biopsy proven acute rejection (BPAR). The incidence of BPAR was 4/9 in Bela+MPA, 0/8 in Bela+low dose Tac and 2/10 in Tac+MPA, P= 0.087. The Bela+low-dose Tac regimen was associated with +8.8 mL/min/1.73 m2increase in eGFR compared to -0.38 mL/min/1.73 m2in Tac+MPA, P= 0.243. One graft loss occurred in the Bela+MPA group. Immunophenotyping of peripheral blood monocyte count (PBMC) showed that CD28+CD4+and CD28+CD8+T cells were higher in Bela+MPA patients with acute rejection compared to patients without rejection, although the difference did not reach statistical significance.

Conclusions

Our data indicate that, in steroid free regimens, low-dose Tac maintenance is needed to prevent rejection when patients are converted to Bela, at least when the maneuver is done early after transplant.
Arginine as the sole nitrogen source for Ostreococcus tauri growth: Insights on nitric oxide synthase enzyme
Authors: Foresi Noelia , Caló Gonzalo , Del Castello Fiorella , Nejamkin Andres , Salerno Graciela , Lamattina Lorenzo , Martínez-Noël Giselle , Correa-Aragunde Natalia
Published: December 2022

Introduction

Photosynthetic organisms respond to nitrogen (N) deprivation with the slowdown of photosynthesis and electron transport resulting in the balance the carbon (C)/N ratio. Under this extreme condition, organisms trigger complex mechanisms to keep growing using different N sources and recycling N containing molecules. In particular, phytoplankton are able to uptake L-arginine (L-Arg) as an organic N source. L-Arg can be assimilated mainly by the arginase, arginine deimidase, arginine decarboxylase or L-amino oxidase pathways.

Results

We analyzed the effect of different N sources on the growth of the green algae Ostreococcus tauri. N starvation caused an inhibition of culture growth and a decrease in chlorophyll content. The addition of L-Arg to an N-deprived medium promotes a sustained growth rate of O. tauri culture and the increase of chlorophyll levels. The transcript level of genes involved in N uptake and metabolism were increased in N-starved condition while the addition of L-Arg as the sole N source reduced their induction. Since the O. tauri genome lacks the classical pathways to metabolize L-Arg, another enzyme/s may be responsible for L-Arg catabolism. Previously, we characterized the nitric oxide synthase (NOS) enzyme from O. tauri (OtNOS) which oxidizes L-Arg producing nitric oxide (NO) and citrulline. The NOS inhibitor L-NAME blocks the effect promoted by L-Arg on N-deprived O. tauri growth. Besides, NO level increased in O. tauri cells growing in L-Arg containing medium, suggesting the participation of OtNOS enzyme in L-Arg metabolism during N starvation.

Discussion

Our hypothesis suggests that, after NOS-dependent Arg degradation, non-enzymatic oxidation of NO produces N oxides (mainly NO2-) that are re-incorporated to the N primary metabolism. As expected, N deprivation increases the lipid content in Ostreococcus. The addition of L-Arg or NO2- as the sole N sources showed a similar increase in lipid content to N deprivation. In summary, our results demonstrate that L-Arg is able to function as N source in Ostreococcus. The evidences on an alternative pathway of N supply and metabolism in a photosynthetic microorganism are discussed. These results could also allow the development of biotechnological tools for increasing lipid production for industry.
Vocalizing humpback whales (Megaptera novaeangliae) migrating from Antarctic feeding grounds arrive earlier and earlier in the Perth Canyon, Western Australia
Authors: Gosby Corinna , Erbe Christine , Harvey Euan S. , Figueroa Landero Marcela Montserrat , McCauley Robert D.
Published: December 2022

Migratory species undertake seasonal, long-distance travel between feeding and breeding grounds, and time their arrivals with high-quality resources. The Breeding Stock D population of humpback whales (Megaptera novaeangliae) migrates from Antarctic to Western Australian waters every austral winter. Based on 16 years (2002-2017) of passive acoustic recordings in the Perth Canyon, Western Australia, the hourly presence/absence of humpback whale vocalizations was used as an indicator of inter-annual changes in migration timing. A trend of earlier arrivals in the Perth Canyon by 1.4 days/year during the northward migration and possibly earlier departures from the Perth Canyon during the southward migration was observed. A distance-based linear model and a generalized linear model (GLM) both identified sea surface temperature (SST) as the most significant predictor for acoustic presence in the Perth Canyon. A 1 °C increase in SST corresponded to a decrease in humpback whale acoustic presence by 4.4 hours/day. Mean SST at the peak of the humpback whale season in the Perth Canyon was 19 °C. Exploratory analysis of the metocean environment of the Antarctic feeding grounds suggested that whales were leaving the Antarctic at the end of the austral summer, as sea ice concentration (SIC) increased and SST decreased. Further research should investigate whether changes in the metocean conditions on Australian breeding grounds correspond to changing departures from the Perth Canyon during the southward migration. If environmental conditions on breeding and feeding grounds change out-of-sync, migrating whales might be unable to arrive at either ground during optimal conditions.
Development of integrated multitrophic aquaculture–based cage rearing system in an underutilized fishing port and its application in marine stock enhancement
Authors: Lee Hung-Tai , Chang Yung-Cheng , Liao Cheng-Hsin , Hsu Te-Hua
Published: December 2022

Human activity and global climate change have severely affected marine ecosystems and fishery resources. Habitat conservation and stock enhancement are considered effective methods. Moreover, with the gradual disappearance of fishery resources, fishing ports have become underutilized spaces. Currently, 73 of the 221 fishing ports in Taiwan are underutilized. Therefore, we, for the first time, developed an integrated multitrophic aquaculture (IMTA)-based cage rearing system suitable for stock enhancement and applied it in an optimal underutilized fishing port after the site evaluation and selection of 17 potential fishing ports fishing. We further tested that hypothesis that hatchery-produced organisms can be reared and monitored appropriately in this cage rearing system with good survival and growth as well as less environmental impact and handling stress. Through the collocation of various release organisms of different trophic levels, the cage rearing system can reduce environmental impacts as evidenced by the steady water quality (stable pH and undetectable levels of ammonia nitrogen, nitrates, and nitrites). As for the fish welfare, this semiartificial rearing system could also reduce the discomforts of hatchery-produced organisms after transportation and facilitate their adaptations to the released environments as evidenced by positive growth and high survival rates (94%–98%). The cultured and naturally grown shellfish and algae on the cage nets could provide habitats for hatchery-produced and wild organisms that facilitate habitat conservation and stock enhancement. Taken together, we have demonstrated that it is feasible to implement this novel IMTA-based cage rearing system in an underutilized fishing port required for marine stock enhancement.
Development of novel Escherichia coli cell-based biosensors to monitor Mn(II) in environmental systems
Authors: Jeon Yangwon , Lee Yejin , Kim Yeonhong , Park Chanhee , Choi Hoon , Jang Geupil , Yoon Youngdae
Published: December 2022

Escherichia coli uses manganese [Mn(II)] as an essential trace element; thus, it has a genetic system that regulates cellular Mn(II) levels. Several genes in the mnt-operon of E. coli respond to intercellular Mn(II) levels, and transcription is regulated by a transcription factor (MntR) that interacts with Mn(II). This study aimed to develop Mn(II)-sensing biosensors based on mnt-operon genetic systems. Additionally, the properties of biosensors developed based on the promoter regions of mntS, mntH, and mntP were investigated. MntR represses the transcription of MntS and MntH after binding with Mn(II), while it induces MntP transcription. Thus, Mn(II) biosensors that decrease and increase signals could be obtained by fusing the promoter regions of mntS/mntH and mntP, with egfp encoding an enhanced green fluorescent protein. However, only the biosensor-based mntS:egfp responded to Mn(II) exposure. Further, E. coli harboring PmntS:egfp showed a concentration-dependent decrease in fluorescence signals. To enhance the sensitivity of the biosensor toward Mn(II), E. coli containing a deleted MntP gene that encodes Mn(II) exporter, was used as a host cell for biosensor development. The sensitivity toward Mn(II) increased by two times on using E. coli-mntP, and the biosensor could quantify 0.01–10 μM of Mn(II). Further, the applicability of Mn(II) in artificially contaminated water samples was quantified and showed >95% accuracy. The newly developed Mn(II) biosensors could detect and quantify the residual Mn(II) from mancozeb in soil samples, with the quantification accuracy being approximately 90%. To the best of our knowledge, this is the first Mn (II)-specific bacterial cell-based biosensor that serves as a valuable tool for monitoring and assessing the risks of Mn(II) in environmental systems.
The gut microbiota as a target to improve health conditions in a confined environment
Authors: Chen Zheng , Wang ZiYing , Li Dan , Zhu Beiwei , Xia Yongjun , Wang Guangqiang , Ai Lianzhong , Zhang Chunhong , Wang Chuan
Published: December 2022

Confined environments increase psychological stress and lead to health problems such as abnormal mood and rhythm disruption. However, the mechanism by which confined environments impact health has remained unclear. Significant correlations have been reported between psychological stress and changes in gut microbiota. Therefore, we investigated the effect of a confined environment on the composition of the gut microbiota by 16s rDNA high-throughput sequencing, and analyzed the correlation between gut microbiota and health indicators such as uric acid (UA), sleep, and mood. We found that the gut microbiota of the subjects clustered into two enterotypes (Bi and Bla), and that the groups differed significantly. There were notable differences in the abundances of genera such as Bifidobacterium, Dorea, Ruminococcus_torques_group, Ruminococcus_gnavus_group, Klebsiella, and UCG-002 (p < 0.05). A confined environment significantly impacted the subjects’ health indicators. We also observed differences in how the subjects of the two enterotypes adapted to the confined environment. The Bi group showed no significant differences in health indicators before and after confinement; however, the Bla group experienced several health problems after confinement, such as increased UA, anxiety, and constipation, and lack of sleep. Redundancy analysis (RDA) showed that UA, RBC, mood, and other health problems were significantly correlated with the structure of the gut microbiota. We concluded that genera such as UCG-002, Ruminococcus, CAG352, and Ruminococcus_torques_group increased vulnerability to confined environments, resulting in abnormal health conditions. We found that the differences in the adaptability of individuals to confined environments were closely related to the composition of their gut microbiota.
Time-course gait pattern analysis in a rat model of foot drop induced by ventral root avulsion injury
Authors: Chan Shu-Yen , Kuo Chi-Wei , Liao Tsai-Tsen , Peng Chih-Wei , Hsieh Tsung-Hsun , Chang Ming-Yuan
Published: December 2022

Foot drop is a common clinical gait impairment characterized by the inability to raise the foot or toes during walking due to the weakness of the dorsiflexors of the foot. Lumbar spine disorders are common neurogenic causes of foot drop. The accurate prognosis and treatment protocols of foot drop are not well delineated in the scientific literature due to the heterogeneity of the underlying lumbar spine disorders, different severities, and distinct definitions of the disease. For translational purposes, the use of animal disease models could be the best way to investigate the pathogenesis of foot drop and help develop effective therapeutic strategies for foot drops. However, no relevant and reproducible foot drop animal models with a suitable gait analysis method were developed for the observation of foot drop symptoms. Therefore, the present study aimed to develop a ventral root avulsion (VRA)-induced foot drop rat model and record detailed time-course changes of gait pattern following L5, L6, or L5 + L6 VRA surgery. Our results suggested that L5 + L6 VRA rats exhibited changes in gait patterns, as compared to sham lesion rats, including a significant reduction of walking speed, step length, toe spread, and swing phase time, as well as an increased duration of the stance phase time. The ankle kinematic data exhibited that the ankle joint angle increased during the mid-swing stage, indicating a significant foot drop pattern during locomotion. Time-course observations displayed that these gait impairments occurred as early as the first-day post-lesion and gradually recovered 7–14 days post-injury. We conclude that the proposed foot drop rat model with a video-based gait analysis approach can precisely detect the foot drop pattern induced by VRA in rats, which can provide insight into the compensatory changes and recovery in gait patterns and might be useful for serving as a translational platform bridging human and animal studies for developing novel therapeutic strategies for foot drop.
How should we define a nociceptor in the gut-brain axis?
Authors: Spencer Nick J. , Hibberd Tim , Xie Zili , Hu Hongzhen
Published: December 2022

In the past few years, there has been extraordinary interest in how the gut communicates with the brain. This is because substantial and gathering data has emerged to suggest that sensory nerve pathways between the gut and brain may contribute much more widely in heath and disease, than was originally presumed. In the skin, the different types of sensory nerve endings have been thoroughly characterized, including the morphology of different nerve endings and the sensory modalities they encode. This knowledge is lacking for most types of visceral afferents, particularly spinal afferents that innervate abdominal organs, like the gut. In fact, only recently have the nerve endings of spinal afferents in any visceral organ been identified. What is clear is that spinal afferents play the major role in pain perception from the gut to the brain. Perhaps surprisingly, the majority of spinal afferent nerve endings in the gut express the ion channel TRPV1, which is often considered to be a marker of “nociceptive” neurons. And, a majority of gut-projecting spinal afferent neurons expressing TRPV1 are activated at low thresholds, in the “normal” physiological range, well below the normal threshold for detection of painful sensations. This introduces a major conundrum regarding visceral nociception. How should we define a “nociceptor” in the gut? We discuss the notion that nociception from the gut wall maybe a process encrypted into multiple different morphological types of spinal afferent nerve ending, rather than a single class of sensory ending, like free-endings, suggested to underlie nociception in skin.
A machine learning-based approach to predicting the malignant and metastasis of thyroid cancer
Authors: Gu Jianhua , Xie Rongli , Zhao Yanna , Zhao Zhifeng , Xu Dan , Ding Min , Lin Tingyu , Xu Wenjuan , Nie Zihuai , Miao Enjun , Tan Dan , Zhu Sibo , Shen Dongjie , Fei Jian
Published: December 2022

Background

Thyroid Cancer (TC) is the most common malignant disease of endocrine system, and its incidence rate is increasing year by year. Early diagnosis, management of malignant nodules and scientific treatment are crucial for TC prognosis. The first aim is the construction of a classification model for TC based on risk factors. The second aim is the construction of a prediction model for metastasis based on risk factors.

Methods

We retrospectively collected approximately 70 preoperative demographic and laboratory test indices from 1735 TC patients. Machine learning pipelines including linear regression model ridge, Logistic Regression (LR) and eXtreme Gradient Boosting (XGBoost) were used to select the best model for predicting deterioration and metastasis of TC. A comprehensive comparative analysis with the prediction model using only thyroid imaging reporting and data system (TI-RADS).

Results

The XGBoost model achieved the best performance in the final thyroid nodule diagnosis (AUC: 0.84) and metastasis (AUC: 0.72-0.77) predictions. Its AUCs for predicting Grade 4 TC deterioration and metastasis reached 0.84 and 0.97, respectively, while none of the AUCs for Only TI-RADS reached 0.70. Based on multivariate analysis and feature selection, age, obesity, prothrombin time, fibrinogen, and HBeAb were common significant risk factors for tumor progression and metastasis. Monocyte, D-dimer, T3, FT3, and albumin were common protective factors. Tumor size (11.14 ± 7.14 mm) is the most important indicator of metastasis formation. In addition, GGT, glucose, platelet volume distribution width, and neutrophil percentage also contributed to the development of metastases. The abnormal levels of blood lipid and uric acid were closely related to the deterioration of tumor. The dual role of mean erythrocytic hemoglobin concentration in TC needs to be verified in a larger patient cohort. We have established a free online tool (http://www.cancer-thyroid.com/) that is available to all clinicians for the prognosis of patients at high risk of TC.

Conclusion

It is feasible to use XGBoost algorithm, combined with preoperative laboratory test indexes and demographic characteristics to predict tumor progression and metastasis in patients with TC, and its performance is better than that of Only using TI-RADS. The web tools we developed can help physicians with less clinical experience to choose the appropriate clinical decision or secondary confirmation of diagnosis results.
Surgery's role in contemporary osteoarticular infection management
Authors: De Marco Giacomo , Vazquez Oscar , Gavira Nathaly , Ramadani Ardian , Steiger Christina , Dayer Romain , Ceroni Dimitri
Published: December 2022

The treatment paradigm for osteoarticular infections (OAIs) has changed drastically over the past 80 years, from the advent of penicillin to the use of broad-spectrum antibiotics. Before these drugs, surgery was the only available treatment for OAIs; today, antibiotic therapy is considered the primary response to them. As a result, surgical treatment of OAIs is thus far more rarely indicated, sometimes even considered outdated and obsolete. However, long experience has taught us that many OAI contexts can still benefit from surgical management, constituting an essential complement to medical treatment. The present article seeks to contextualize this discussion by providing a chronological review of the surgical treatments used in cases of OAI and describing the quality of evidence supporting their rehabilitation in well-established situations.
Case report: Early-onset renal failure as presenting sign of Lesch-Nyhan disease in infancy
Authors: Yang Lianlian , Guo Hui
Published: December 2022

Lesch–Nyhan disease (LND) is a rare X-linked recessive disease caused by pathogenic mutations of the HPRT1 gene. The typical clinical manifestations include cerebral palsy, intellectual disability, dysarthria, self-injurious behavior, and gouty arthritis in children. This report describes a Chinese boy aged 2 months and 7 days with a significantly elevated uric acid concentration accompanied by renal dysfunction and, notably, brain imaging changes. Whole-exome sequencing revealed a hemizygous mutation of HPRT1 in nucleotide 508 from cytosine to thymine (c.508C > T), resulting in a nonsense mutation (p.R170X). The incidence of LND is extremely low in China, and hyperuricemia is a common clinical manifestation. Therefore, the possibility of LND should be considered in children with increased uric acid in infancy accompanied by brain imaging changes or neurological dysfunction. Moreover, genetic testing is needed to provide adequate genetic counseling to the family, and should be conducted as early as possible in such children to avoid misdiagnosis or delayed diagnosis.