bluuebunny/crossref_metadata_2025 huggingface dataset:
Amino acid nitrogen stable isotopes as biomarkers of coastal phytoplankton assemblages and food web interactions
Authors: Sabadel AJM , Décima M , McComb K , Meyers M , Barr N , Gall M , Safi K , Law CS
Published: April 2022

Marine phytoplankton and zooplankton face rapidly changing environments in the face of global warming and climate change. We investigated the effect of warmer water and lower pH conditions—projected for New Zealand coastal waters at the start of the next century—on both phytoplankton and zooplankton in a 20 d mesocosm experiment to determine whether amino acid stable isotopes could be used as biomarkers of environmental change. We also assessed whether key environmental drivers, such as those linked to climate change, altered the processing of amino acids at the base of the food web. Despite changes in phytoplankton biomass and community composition, we found no significant difference in either particulate organic matter (POM) bulk or amino acid-specific δ15N values, indicating that the trophic status of POM was not significantly influenced by lower pH and warming. Threonine δ15N values were the most sensitive to changes in the phytoplankton community and showed correlations with diatoms (positive) and small flagellates (negative), demonstrating potential as a biomarker for detecting changes related to these phytoplankton groups and thus making threonine a promising indirect indicator of climate change. Finally, δ15NPhe values tracked changes in the lower food web, likely due to faster turnover times, showing its valuable role as a tracer of the nitrogen baseline, even during accelerated metabolism in zooplankton.
Facial Swelling as a Presenting Sign of Cholangiocarcinoma
Authors: Khaladkar Sanjay M. , Dilip Darshana , Chanabasanavar Vijetha , Bethireddy Nagireddy , Lamghare Purnachandra
Published: April 2022

Cholangiocarcinoma is a rare primary malignancy of the biliary tree, which usually presents late in the course of disease with jaundice, upper right quadrant pain, and cachexia. They frequently metastasise in the lungs, liver, bones, adrenals, peritoneum, and retroperitoneal lymph nodes. The incidence of cutaneous dissemination from cholangiocarcinoma is extremely rare, with the scalp being the commonest distant site of skin metastasis. The authors report the case of a 44-year-old female with Stage IV hilar cholangiocarcinoma, who presented primarily with tender facial swelling, prompting investigation and subsequent diagnosis. To the authors’ knowledge, this case is the first report of a cholangiocarcinoma presenting as facial metastasis. It highlights the need for early characterisation of cutaneous lesions, which are likely to be of neoplastic origin using histology, immunohistochemistry, and PET-CT scans, and reminds that biliary tree neoplasms are possible primary malignancies in cases of skin metastasis, especially in the head and neck region.
Comparison Between Visual and Ultrasonic Tomography Joint Deployment Detection Methods
Authors: Wallace Michael , Burnham Thomas
Published: April 2022

Thin bonded concrete overlays placed on existing asphalt (BCOA) pavements perform best when they are designed and constructed with small square panels. The closely spaced contraction joints help to control the location of slab cracking that develops due to the restraint stresses caused by concrete shrinkage and thermal contraction, reflective cracking forces, differential movement between the concrete overlay and asphalt, and curling and warping stresses. These joints are only able to fulfill their function if they deploy shortly after hardening of the concrete. Due to common observations of sequential joints not deploying, experimentation has begun with applying early loads to the panels to encourage more frequent deployment. While visual observation of joint deployment along the side of the concrete overlay is possible before shouldering material is placed, it becomes difficult thereafter. Questions also arise whether visual observation of a cracked joint on the side of the pavement reflects that the joint is fully deployed across the lanes. This study examined the efficacy of visual joint deployment detection along the side of a BCOA project that had been loaded early, compared to ultrasonic tomography conducted across those same joints. Analysis shows both that visual observations and ultrasonic tomography can be used to reliably detect joint deployment, and that it is uncommon that joint deployment is not fully engaged across lanes.
Eski Orta-Asya Türk Kamu Hukuku’nda Kağanların Görev ve Sorumlulukları
Authors: PAMİR Aybars
Published: April 2022

Eski Orta – Asya Türk Kamu Hukuku’nun temel sujesi kağandı. Devlet onun kişiliğinde vücut bulmakta, egemenlik hakkı da doğrudan onun tarafından kullanılmaktaydı. Gök Tanrı tarafından verildiğine inanılan kut kağanı yarı-kutsal bir niteliğe büründürmüştü. Kağan, kutu sayesinde devletini korumak, halkına gece-gündüz hizmet etmek, kurultay toplamak gibi çok sayıda önemli görevi üstlenmiş durumdaydı
TİCARİ İŞLEMLERDE TAŞINIR REHİNLERİ ARASINDA SIRA
Authors: YILDIZ Kübra
Published: April 2022

KOBİ’lerin finansman sağlamak noktasında yaşadıkları güçlükleri bertaraf edebilmek amacıyla hazırlanan ve yürürlüğe giren 6750 Sayılı Ticari İşlemlerde Taşınır Rehni Kanunu pek çok sorunu da beraberinde getirmiştir. Türk Medeni Kanununda taşınır mallar bakımından kabul edilmiş olan teslime bağlı rehnin yanı sıra söz konusu kanun ile sicilli rehne imkân tanınmış olması, ticari işlemler kapsamındaki bir taşınır rehninin teslime bağlı olarak gerçekleştirilmesine engel değildir. Ayrıca bir taşınır üzerinde aynı anda birden fazla sicilli rehnin kurulması da mümkündür. Bu tür durumlarda rehin haklarının sırası bakımından nasıl bir hukuki sonuca varılacağının belirlenmesi, kanun koyucunun benimsediği sisteme bağlıdır. 6750 sayılı Kanunda hem sabit derece sistemi hem de ilerleme sistemine yer verildiği görülmektedir. Hangi hallerde hangi sisteme göre belirleme yapılacağının tespiti ve bu doğrultuda uygun sonuca ulaşılması şüphesiz ki dikkatli bir tahlili gerektirmektedir. Bunlarla beraber bazı durumlarda var olan rehin süresinin uzatılması ihtimali ile de karşılaşılmaktadır. Bu halde süresi uzatılan rehin hakkının diğer rehin hakları karşısında pozisyonunu koruyabilip korumayacağının incelenmesi önem taşımaktadır. Son olarak, rehne konu olan bir taşınırın getirilerinin bu rehin hakkından nasıl etkileneceğinin tespiti de gerekmektedir.
Aristotle’s Solution to Zeno’s Arrow Paradox and its Implications
Authors: Pemberton John M.
Published: April 2022

Aristotle’s solution to Zeno’s arrow paradox differs markedly from the so called at-at solution championed by Russell, which has become the orthodox view in contemporary philosophy. The latter supposes that motion consists in simply being at different places at different times. It can boast parsimony because it eliminates velocity from the ontology. Aristotle, by contrast, solves the paradox by denying that the flight of the arrow is composed of instants; rather, on my reading, he holds that the flight is a unity which is ontologically prior to the temporal parts that may be abstracted from it. I label this position temporal holism; and an entity that is ontological prior to its temporal parts lasting. Lasting, I argue, is the key to Aristotle’s solution to the arrow paradox, but it has received insufficient attention in the relevant literature. I therefore set out here to investigate lasting and highlight its major role in Aristotle’s metaphysics more broadly, and in his solution to other problems of change (e.g. the reality of change). I show, too, how lasting within a contemporary context underwrites a parsimonious and intuitive solution to the arrow paradox that retains instantaneous velocity, and hence (inter alia) solves a problem for those who think velocity is required within the ontology to underwrite certain causal roles.
Translating Surrealist Poetics
Authors: Brzostowska-Tereszkiewicz Tamara
Published: April 2022

It can be argued that translations of Surrealist works entail obstacles and contradictions specific exclusively to this mode of literary production. What renders ‘Surrealist translations’ incomparable with other interlingual adventures of the literary avant-garde is the irreducible opposition between translation as a norm-governed, self-reflexive and intersubjective activity and ‘pure psychic automatism’ unconstrained by linguistic and cultural factors other than effectiveness of artistic self-expression. Hence, the translational mimesis involves mimicking the original creative process rather than its product. Indeed, the translators of Surrealist works have often no other choice than to take ‘unmimetic turns’ to convey the oneiric appeal, aleatoricity and figurativeness of the originals. Moreover, the translations of Surrealist works owe their distinctiveness to the neutralization of the opposition between foreignization and domestication in the sense established in translation studies. Their main task is rather to sustain the effect of defamiliarization and to recreate the unexpected clashes of entire semantic fields that animate Surrealist poetry. Of no less importance are the language- and culture-specific possibilities of recreating Surrealist ‘metaphors’ based on divergence and contradiction rather than correlations. Translation as a product of rational decision-making processes inevitably stumbles over the Surrealist metaphor born out of the irrational and coincidental.
Dictionary (noun) – A Revolutionary Act or Performance: Socio-Political Lessons from China on the Power and (Un)Translatability of Words
Authors: Odom Glenn
Published: April 2022

Three recent texts emerging from distinct parts of China, all ‘dictionaries’ of sorts, each serve as a marker of the revolutionary potential of translation within their own contexts, but also as a marker of the limitations to translating the politics of translation to a world reader. At a moment when the Han-centric CCP (Chinese Communist Party) is reducing regional autonomy and forcing citizens into re-education camps, questions of language use and (un)translatability can have immediate and concrete consequences. The official and unofficial multiplicity of Chinese conceptions of ethnicity and nationality provide a necessary background for an understanding of the severity of the consequences of translation in the contemporary contexts. Likewise, a history of the dictionary in China provides insights as to why the dictionary form has been adopted to varying degrees by multiple contemporary texts. The parallax created between the Chinese contexts and world contexts of these texts, however, serves as a stark reminder of the potential bounds of the world literature paradigm.
IMPLEMENTASI KEBIJAKAN SISTEM INFORMASI MANAJEMEN KEPEGAWAIAN PADA BADAN KEPEGAWAIAN DAN PENGEMBANGAN SUMBER DAYA MANUSIA KABUPATEN BOMBANA
Authors: Kamal Muhamad , Basri Muhammad , Jopang Jopang
Published: April 2022

Penelitian ini bertujuan untuk mendeskripsikan dan menganalisis implementasi kebijakan sistem informasi manajemen kepegawaian pada Badan Kepegawaian dan Pengembangan Sumber Daya Manusia Kabupaten Bombana. Penelitian ini merupakan jenis penelitian deskriptif kualitatif dengan informan yang berjumlah sebanyak 9 orang yang ditentukan secara purposive sampling. teknik pengumpulan data dilakukan dengan cara wawancara mendalam, observasi dan studi dokumentasi. Teknik analisis data dalam penelitian ini yaitu reduksi data, penyajian data dan penarikan kesimpulan/verifikasi. Hasil Penelitian ini menunjukkan bahwa implementasi kebijakan Sistem Informasi Manajemen Pegawai  pada Badan Kepegawaian dan Pengembangan Sumber Daya Manusia Kabupaten Bombana ditinjau secara umum pada dasarnya telah dilaksanakan dengan didukung ketersediaan perangkat keras, perangkat lunak, sistem jaringan komputer dan sumber daya manusia, namun ketersediaan database pegawai pada Badan Kepegawaian dan Pengembangan Sumber Daya Manusia Kabupaten Bombana belum lengkap. Kata Kunci: Implementasi, Kebijakan, Sistem Informasi
IMPLEMENTASI E-GOVERNMENT DALAM PENGADAAN BARANG DAN JASA PEMERINTAH KABUPATEN WAKATOBI
Authors: Ikrar Rabil , Banga Wempy , Alam Syamsul
Published: April 2022

Penelitian ini bertujuan untuk mendeskripsikan dan menganalisis inplementasi E – Government dalam pengadaan barang dan jasa di Kantor Sekretariat Daerah Wakatobi. Penelitian ini merupakan jenis penelitian deskriptif dengan pendekatan kualitatif. Informan dalam penelitian ini berjumlah 3 orang yang dipilih secara purposive sampling.Teknik pengumpulan data dalam penelitian ini yaitu wawancara dengan informan yang telah dipilih serta dan studi dokumentasi. Teknik analisis data yang digunakan analisis deskripsi kualitatif. Hasil penelitian menujukkan bahwa implementasi E-Government dalam pengadaan barang dan jasa secara elektronik yang diselenggarakan oleh Unit Layanan Pengadaan Kabupaten Wakatobi dilakukan berdasarkan empat prinsip yaitu 1) transparansi, dalam artian bahwa semua tahapan pelaksanaan pengadaan barang dan jasa dilakukan secara terbuka kepada msayarakat, 2) bersaing, dengan sistem elektronik dapat menciptakan persaingan yang sehat bagi para pendaftar, 3) adil/tidak deskriminatif, semua penyedia diberlakukan secara adil tanpa memihak dengan siapapun dari tahap pendataran sampai pengemuman pemenan dan 4) akuntabel, semua pelaksanaan pengadaan barang dan jasa dilakukan oleh Unit Laayanan Pengadaan Kabupaten Wakatobi sesuai Perspres 54 tahun 2010 dengan berpedoman pada SOP pelayanan pengadaan barang dan jasa secara elektronik. Kata Kunci: Implementasi, E- Government, Pengadaan barang dan Jasa
MANAJEMEN PENGEMBANGAN PARIWISATA PADA DINAS PARIWISATA PROVINSI SULAWESI TENGGARA
Authors: Dewi K. Siregar St. Rabiah , Utha Arifin , Kadir H. Abdul
Published: April 2022

Tujuan penelitian ini adalah untuk mendeskripsikan manajemen   pariwisata  di Provinsi Sulawesi Tenggara. Penelitian ini menggunakan pendekatan penelitian kualitatif. Teknik pengumpulan data menggunakan metode  wawancara mendalam dan  studi dokumen. Teknik analisis data menggunakan model analisis data interaktif:  data collection, data reduction, data display dan conclusion drawing/verification. Hasil penelitian menunjukkan bahwa manajemen   pariwisata di Provinsi Sulawesi Tenggara dapat terlaksana melalui 3 dimensi manajemen pengembangan yaitu:  (a) Perencanaan. Pemerintah Provinsi Sulawesi Tenggara membuat perencanaan pengembangan pariwisata pada 4 aspek yaitu pengembangan destinasi wisata yaitu Pulau Bokori  dan watersport Kendari, perencanaan pemasaran pariwisata melalui promosi, festival seni budaya, dan  pameran hasil karya ekonomi kreatif. (b) Implementasi pariwisata melalui 4 aspek yaitu  melaksanakan pengembangan pariwisaya yaitu melakukan pemasaran pariwisata melalui promosi dan pameran, pengembangan destinasi wisata yakni membangunan sarana dan prasarana, pengembangan sumberdaya pariwisata ekonomi kreatif  dan  pengembangan  ekonomi kreatif dengan melakukan pelatihan masyarakat disekitar objek wisata dan (c) Evaluasi  pariwisata, pemerintah provinsi  mampu  membangun  destinasi wisata Pulau Bokori dan destinasi wisata watersport Kendari dengan  hasil 100 %,  berhasil melaksanakan promosi pariwisata melalui pameran  ekonomi kreatif, festival seni dan budaya, expo dan promosi budaya melalui pameran budaya di Prancis dan China. Kata Kunci : Manajemen, Pengembangan,  Pariwisata Bokori, perencanaan pemasaran pariwisata
IMPLEMENTASI KEBIJAKAN PENGAWASAN PENEMPATAN TENAGA KERJA INDONESIA OLEH PERUSAHAAN JASA TENAGA KERJA INDONESIA (Studi pada Dinas Tenaga Kerja dan Transmigrasi Kabupaten Konawe)
Authors: Rodi Rodi , Kamaluddin Murdjani , Bake Jamal
Published: April 2022

Tujuan penelitian adalah mendeskripsikan implementasi kebijakan pengawasan dalam penempatan Tenaga Kerja Indonesia   (TKI)  oleh Perusahaan Jasa Tenaga Kerja Indonesia (PJTKI)  pada Dinas Tenaga Kerja  dan Transmigrasi Kabupaten Konawe. Penelitian ini menggunakan pendekatan penelitian kualitatif. Informan penelitian adalah pegawai Dinas Tenaga Kerja dan Transmigrasi Kabupaten Konawe dan PJTKI. Informan penelitian ditetapkan dengan purposive sampling. Teknik pengumpulan data dengan cara wawancara dan studi dokumentasi. Analisis penelitian menggunakan analisis data interaktif.  Hasil penelitian menunjukkan bahwa  Implementasi kebijakan pengawasan dalam penempatan TKI oleh PJTKI. pada Dinas Tenaga Kerja dan Transmigrasi Kabupaten Konawe dapat terlaksana melalui: (a) pengawasan langsung meliputi pengawasan pendaftaran  dan Seleksi Calon TKI, pengawasan dokumen, pengawasan verifikasi kelengkapan dokumen ketenagakerjaan calon TKI ke luar negeri, pengawasan pendidikan dan pelatihan  kerja calon TKI, pengawasan uji kompetensi, pengawasan penandatanganan penempatan kerja dan perjanjian kerja calon TKI, pengawasan penyelesaian permasalahan TKI pra dan purna penempatan. (b) pengawasan tidak langsung meliputi:  pengawasan pelayanan proses pemulangan TKI dan pengawasan pemulangan TKI sebanyak 30 orang tahun 2018 dan sebanyak 255 orang tahun 2019 asal Kabupaten Konawe oleh PJTKI. Kata Kunci: Impelemntasi, Kebijakan Pengawasan, Penempatan, TKI
IMPLEMENTASI KEBIJAKAN PENGELOLAAN PAJAK HOTEL DALAM MENINGKATKAN PENDAPATAN ASLI DAERAH (PAD) KOTA KENDARI
Authors: Fajarullah Fajarullah , Banga Wempy , Larisu Zulfiah
Published: April 2022

Penelitian bertujuan mendeskripsikan dan menganalisis implementasi kebijakan pengelolaan pajak hotel dalam meningkatkan Pendapatan Asli Daerah Kota Kendari.  Metode penelitian menggunakan pendekatan kualitatif, penentuan informan menggunakan teknik purposive sampling dengan informan sebanyak 13 orang.  Penelitian melalui wawancara, observasi dan dokumentasi dan dianalisis secara deskriptif kualitatif yaitu memberikan gambaran menyeluruh terhadap situasi sosial yang diteliti.  Hasil penelitian menunjukan bahwa implementasi kebijakan pengelolaan pajak hotel Kota Kendari dalam meningkatkan Pendapatan Asli Daerah melalui Badan Pengelola Pajak dan Retribusi Daerah Kota Kendari  melalui  Peraturan Daerah Nomor 02 Tahun 2011 tentang Pajak dan Retribusi telah berjalan dengan baik ditunjukan dengan pencapaian target pajak hotel dari 2016 sampai 2018.   Namun perlu adanya peningkatan pelayanan dari sektor sarana dan prasarana yang menunjang kemudahan pelayanan pajak. Faktor yang mempengaruhi implementasi kebijakan pengelolaan pajak Kota Kendari meliputi idealisasi kebijakan, target kelompok, organisasi pelaksana, dan faktor lingkungan.  Peningkatan pencapaian pajak oleh Pemerintah perlu memberikan pengawasan dan sosialisasi terhadap hak dan  kewajiban wajib pajak.Kata Kunci : Implementasi Kebijakan, Pengelolaan Pajak Hotel, Pendapatan Asli Daerah
IMPLEMENTASI PERATURAN DAERAH TENTANG KETERTIBAN UMUM (KASUS PENATAAN PEDAGANG KAKI LIMA DIKAWASAN PASAR RAYA MEKONGGA KABUPATEN KOLAKA)
Authors: Cahyadi Muhammad Irwan , Kadir Abdul , Utha Arifin
Published: April 2022

Penelitian ini bertujuan untuk mendeskripsikan dan menganalisis implementasi penegakkan ketertiban umum dalam rangka penataan pedagang kaki lima di kawasan pasar Mekongga Kabuptaen Kolaka. Penelitian ini menggunakan pendekatan kualitatif dengan informan yang berjumlah 10 orang. Data dalam penelitian ini diperoleh melalui wawancara dan studi pustaka, data yang diperoleh kemudian dianalisis secara kualitatif melalui analisis interaktif yang terdiri dari reduksi data, penyajian data dan penarikan kesimpulan. Hasil penelitian ini menunjukkan bahwa Implementasi penegaggaan ketertiban umum di Kabupaten Kolaka, khususnya terkait dengan Penataan Pedagang Kaki Lima di Kawasan Pasar Raya Kabupaten Kolaka belum maksimal, baik dari pelaksanaan sosialiasasi maupun pada pelaksanaan penegakkan kebijakan Ketertiban Umum yang tertuang dalam Peraturan Daerah Nomor 32 tentang Ketertiban Umum di Kabupaten Kolaka, khususnya  penertiban Pedagang Kaki Lima  yang ada di Kawasan  Pasar Raya Kabupaten Kolaka.Kata Kunci: Implementasi, Peraturan Daerah, Pedagang Kaki Lima
Are Commonplace Chiral Metal Complexes Unsuitable for Metamaterials?
Authors: Yoshiyuki Sato , Daisuke Nakane , Takashiro Akitsu
Published: April 2022

Among typical metamaterials, we focus on the light "function" and chiral "element" in this chiral light metamaterial minireview. The authors are interested in inorganic materials, especially transition metal complexes. Metal complexes are compounds that have been studied for a long time for their optical properties (light absorption) and chirality (chiroptical spectroscopy, structural crystal chemistry, and asymmetric catalytic reactions). However, since the unit is a "molecule", few examples as (optical) metamaterials have been reported to date. Is it possible to add a function as a composite material using one method? No, the functions resulting from the nano pattern are very difficult to retrofit. Is there a way to fuse the rich compounds at the boundary between inorganic and organic with state-of-the-art optical metamaterials?
WOMEN IN THE EARLY DAYS OF PHARMACY IN GREAT BRITAIN
Authors:   Departamento de Geometría y Topología. Facultad de Matemáticas. Universidad de Sevilla (Spain), Valdés Juan Núñez
Published: April 2022

This paper deals with the beginnings and historical evolution of Pharmacy studies in Great Britain and on the role played by the first women who practiced the profession there, The circumstances of that time, which made very difficult for a woman to work in that area, the biography of the first English woman licensed in Pharmacy, Fanny Deacon, and the biographies of the women who followed her as graduates in Pharmacy in Great Britain are commented, detailing not only their personal data but also the impact they had on the evolution and development of Pharmacy studies in their country. These women were Alice Vickery, Isabella Skinner Clarke, Margaret Elizabeth Buchanan, Rose Coombes Minshull and Agnes Thompson Borrowman.The main objective of the paper is to reveal the figures of these first women in Pharmacy in Great Britain to society, To do this, the methodology used has been the usual in researches of this type: search of data on these women in bibliographical and computer sources, as well as in historic archives. As the main results, the biographies of these pioneers pharmacist women mentioned above have been elaborated
Experimental Research on Electrical Conductivity of the Olivine-Ilmenite System at High Temperatures and High Pressures
Authors: Sun Wenqing , Dai Lidong , Hu Haiying , Wang Mengqi , Hu Ziming , Jing Chenxin
Published: April 2022

Ilmenite is a common metallic oxide distributed in the mafic rocks from the Earth’s upper mantle, and thus the effect of ilmenite contents on the electrical structures of the Earth’s upper mantle should be investigated in detail. Electrical conductivities of the olivine–ilmenite systems with various contents of ilmenite (VIlm = 4, 7, 10, 11 and 15 vol%) and pure ilmenite aggregates were measured using a complex impedance spectroscopic technique at 1.0–3.0 GPa and 773–1273 K. Electrical conductivities of the olivine–ilmenite systems increased with increasing temperatures in different degrees, conforming to the Arrhenius law. With the rise of pressure, the conductivities of the olivine–ilmenite systems slightly increased. According to the significant change of the conductivities, the percolation threshold of ilmenite grains in the olivine–ilmenite systems was proposed to be ∼ 11 vol%. Isolated ilmenites moderately influence the conductivities of olivine aggregates, but the interconnected ilmenites dramatically enhanced the conductivities of the olivine–ilmenite systems. The conductivities of the olivine aggregates with 11 vol% ilmenites were about 1.5–3 orders magnitude higher than those of 10 vol% ilmenites-bearing olivine aggregates. Small polarons were proposed to be the dominant charge carriers for olivine aggregates with isolated ilmenites (activation enthalpies: 0.62–0.89 eV) and interconnected ilmenites (activation enthalpies: 0.15–0.20 eV). Furthermore, the conductivity–depth profiles of olivine–ilmenite systems in the Earth’s upper mantle were constructed, providing an important constraint on the electrical structures of the Earth’s interior.
Effect of Hemoglobin A1c Trajectories on Future Outcomes in a 10-Year Cohort With Type 2 Diabetes Mellitus
Authors: Ma Chifa , Zhang Weinan , Xie Rongrong , Wan Gang , Yang Guangran , Zhang Xuelian , Fu Hanjing , Zhu Liangxiang , Lv Yujie , Zhang Jiandong , Li Yuling , Ji Yu , Gao Dayong , Cui Xueli , Wang Ziming , Chen Yingjun , Yuan Shenyuan , Yuan Mingxia
Published: April 2022

Background

Hemoglobin A1c (HbA1c) variability may be a predictor of diabetic complications, but the predictive values of HbA1c trajectories remain unclear. We aimed to classify long-term HbA1c trajectories and to explore their effects on future clinical outcomes in a 10-year cohort with type 2 diabetes mellitus (T2DM).

Methods

A total of 2,161 participants with T2DM from the Beijing Community Diabetes Study were included. The 10-year follow-up was divided into two stages for the present data analysis. Stage I (from 2008 to 2014) was used to identify the HbA1c trajectories and to calculate the adjusted SD of HbA1c (HbA1c-adjSD), or the coefficient of variation of HbA1c (HbA1c-CV). Stage II (from 2014 to 2018) was used to collect the records of the new occurrence of diabetes-related clinical outcomes. Latent growth mixture models were used to identify HbA1c trajectories. Cox proportional hazards models were used to explore the relationship between HbA1c trajectories, HbA1c-adjSD, or HbA1c-CV and the future outcomes.

Results

Three HbA1c trajectories were identified, including low stable (88.34%), gradual decreasing (5.83%), and pre-stable and post-increase (5.83%). Either the risk of death or the chronic complications were significantly higher in the latter two groups compared to the low stable group after adjustment for average HbA1c and other traditional risk factors, the adjusted hazard ratios (HRs) for renal events, composite endpoint, and all-cause death for the pre-stable and post-increase group were 2.83 [95%CI: 1.25–6.41, p = 0.013], 1.85 (95%CI: 1.10–3.10, p = 0.020), and 3.01 (95%CI: 1.13–8.07, p = 0.028), respectively, and the adjusted HR for renal events for the gradual decreasing group was 2.37 (95%CI: 1.08–5.21, p = 0.032). In addition, both univariate and multivariate Cox HR models indicated that participants in the fourth and third quartiles of HbA1c-CV or HbA1c-adjSD were at higher risk of renal events compared to participants in the first quartile.

Conclusions

HbA1c trajectories, HbA1c-CV, and HbA1c-adjSD could all predict diabetes-related clinical outcomes. HbA1c trajectories could reflect long-term blood glucose fluctuation more intuitively, and non-stable HbA1c trajectories may predict increased risk of renal events, all-cause death, and composite endpoint events, independent of average HbA1c.
Gender Differences Between the Phenotype of Short Stature and the Risk of Diabetes Mellitus in Chinese Adults: A Population-Based Cohort Study
Authors: Song Wei , Hu Yaqin , Yuan Jiao , Wei Ying , Cheng Zongyou , Liu Jingdong , Xu Jixiong , Wang Xiaoyu
Published: April 2022

Objective

Previous studies have shown that there are significant regional and gender differences in the association between the phenotype of short stature and diabetes mellitus (DM). The purpose of this study was to investigate the gender difference between the phenotype of short stature and the risk of DM in the Chinese population.

Methods

The sample included 116,661 adults from 32 locations of 11 cities in China, of which the average height of men and women was 171.65 and 160.06 cm, respectively. Investigators retrospectively reviewed annual physical examination results for follow-up observations and set confirmed DM events as the outcome of interest. Multivariate Cox regression, restricted cubic spline, and piecewise regression models were used to check the association between height and DM risk.

Results

During an average observation period of 3.1 years, there were 2,681 of 116,661 participants who developed new-onset DM, with a male to female ratio of 2.4 to 1. After full adjustment for confounders, we confirmed that there was a significant negative correlation between height and DM risk in Chinese women (HR per 10 cm increase: 0.85, 95% CI: 0.74–0.98), but not in men (HR per 10 cm increase: 1.16, 95% CI: 0.98–1.14). Additionally, through restricted cubic spline and piecewise regression analysis, we determined that the height of 157–158 cm may be the critical point for short stature used to assess the risk of DM in Chinese women.

Conclusions

In the Chinese population, female short stature phenotype is related to increased DM risk, among which 157–158 cm may be the saturation effect point of female short stature for predicting DM risk.
Tunable 2D Nanomaterials; Their Key Roles and Mechanisms in Water Purification and Monitoring
Authors: Fatima Jawaria , Shah Adnan Noor , Tahir Muhammad Bilal , Mehmood Tariq , Shah Anis Ali , Tanveer Mohsin , Nazir Ruqia , Jan Basit Latief , Alansi Saleh
Published: April 2022

Water supplies around the world are currently heavily polluted by heavy-metal chemicals, synthetic dyes, and other toxic pollutants released by major factories rather than typical household waste. This pollution necessitates adequate monitoring to protect natural water sources. There are various wastewater treatment methods available, including nanotechnology, i.e., two dimensional (2D) nanomaterials. Rising 2D nanomaterials including graphene, g-C3N4, MoS2, MXene, black phosphorus, and h-BN have exhibited an unparalleled surface-to-volume ratio, promising ultralow usage of material, ultrafast handling time, and ultrahigh treatment performance for cleaning, and monitoring of water. We provide a current overview of tunable 2D nanomaterials and their uses in water management. A brief description of 2D nanomaterials, their types, synthesis strategies and salient features involved in water management is provided. Furthermore, application of 2D nanomaterial in different processes of water treatment such as pollutants adsorption, filtration, disinfection, photocatalysis are discussed in detail. Likewise, the potential of 2D nanomaterials to be used in water quality monitoring gadgets like fluorescent sensors, colorimetric sensors, electrochemical sensors, and field-effect transistors are also explored. The study ends with a look at the current problems, limitations and future prospectus associated with the use of 2D material in water management. The importance of clean and fresh water to upcoming generations will bring new light and innovations to this emerging sector, allowing it to improve the quality and accessibility of water treatment while also ensuring global water supplies in an increasing part of the world.
Mind the Gap: Reach and Mechanical Diversity of Searcher Shoots in Climbing Plants
Authors: Hattermann Tom , Petit-Bagnard Laureline , Heinz Christine , Heuret Patrick , Rowe Nick P.
Published: April 2022

Climbing plants need to reach supports and position their leaves for light capture. Vines and lianas develop a large diversity of self-supporting shoots among diverse species and different kinds of attachment. A searcher’s reach is a crucial trait for colonising supports in complex three-dimensional spaces. We explore the reach capacity and diversity of searcher shoots among representative temperate and tropical climbing plants. We investigate the overall range of variation between short- and long-reach searchers; the mechanical and anatomical organisations underlying reach capacities; how searcher architectures are linked to different climbing strategies such as stem twining, tendril climbing, root climbing, and branch-angle-hook climbing. We investigated reach and mechanical and anatomical organisations (stem rigidity and stiffness, stem and tissue geometry) in 29 climbing plant species from temperate and tropical habitats. Searchers show a wide range of maximal reach per species from 0.1 to 2.5 m. Flexural rigidity (EI) at the base of searchers increased with reach length; overall this increase was proportional although some longest-reaching shoots develop proportionally thinner searcher bases with higher stiffness [structural Young’s modulus (Estr)] than shorter-reach shoots. Bases of short-reach searchers rely more on primary tissues compared to long-reach shoots, which rely more on wood production. We identified different mechanical architectures for a given reach capacity across all species. These are linked to different kinds of attachment mechanisms, support foraging, and possibly leaf display. Plants attaching by twining of the main stem showed a wide range of reach capacity. They also developed lighter, more slender, less rigid, but generally relatively stiff (higher Estr) shoots compared with tendril climbers and branch-angle-hook climbers. Differences in the mechanical architecture of searcher shoots in climbing plants are informative for understanding how diverse climbing plant species explore and colonise different kinds of three-dimensional spaces. This is a key feature that distinguishes different habitat preferences. We discuss how such knowledge is not only important for understanding functional biology and ecology of climbing plants but is also of interest for developing new technologies in soft robotics that mimic climbing plants that can navigate through unstructured environments.
Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients
Authors: Gross David-Alexandre , Tedesco Novella , Leborgne Christian , Ronzitti Giuseppe
Published: April 2022

One of the major goals of in vivo gene transfer is to achieve long-term expression of therapeutic transgenes in terminally differentiated cells. The extensive clinical experience and the recent approval of Luxturna® (Spark Therapeutics, now Roche) and Zolgensma® (AveXis, now Novartis) place vectors derived from adeno-associated viruses (AAV) among the best options for gene transfer in multiple tissues. Despite these successes, limitations remain to the application of this therapeutic modality in a wider population. AAV was originally identified as a promising virus to derive gene therapy vectors because, despite infecting humans, it was not associated with any evident disease. Thee large proportion of AAV infections in the human population is now revealing as a limitation because after exposure to wild-type AAV, anti-AAV antibodies develops and may neutralize the vectors derived from the virus. Injection of AAV in humans is generally well-tolerated although the immune system can activate after the recognition of AAV vectors capsid and genome. The formation of high-titer neutralizing antibodies to AAV after the first injection precludes vector re-administration. Thus, both pre-existing and post-treatment humoral responses to AAV vectors greatly limit a wider application of this gene transfer modality. Different methods were suggested to overcome this limitation. The extensive preclinical data available and the large clinical experience in the control of AAV vectors immunogenicity are key to clinical translation and to demonstrate the safety and efficacy of these methods and ultimately bring a curative treatment to patients.
Case Report: “Primary Immunodeficiency”—Severe Autoimmune Enteropathy in a Pediatric Heart Transplant Recipient Treated With Abatacept and Alemtuzumab
Authors: Kalaidina Elizaveta , Utterson Elizabeth C. , Mokshagundam Deepa , He Mai , Shenoy Shalini , Cooper Megan A.
Published: April 2022

Disorders of immune dysregulation following heart transplantation in children have been reported; however, the management of such disorders remains uncertain and challenging. In this case report, we describe a clinical course of a child with severe autoimmune enteropathy after a heart transplant in infancy and detail a treatment approach with abatacept and alemtuzumab. A 21-month-old girl with a medical history of congenital dilated cardiomyopathy and heart transplantation at 2 months was evaluated for chronic hematochezia. The patient underwent an extensive workup, including endoscopic biopsy which showed crypt apoptosis, similar to that seen with graft-versus-host disease (GVHD). Results of her immune workup were consistent with status post-thymectomy but also demonstrated evidence of immune dysregulation. Specifically, her immune phenotype at diagnosis demonstrated T-cell lymphopenia, restricted TCR repertoire and skewing of T-cell compartment toward memory phenotype, increase in serum soluble ILR2a, and hypergammaglobulinemia. In the absence of response to more standard immune modulation, the patient was treated with CTLA4-Ig (abatacept), followed by a combination of abatacept and a JAK inhibitor and, finally, a combination of abatacept and alemtuzumab. Following therapy with alemtuzumab, the patient achieved remission for the first time in her life. Her clinical course was complicated by a relapse after 6 months which again readily responded to alemtuzumab. Ultimately, despite these remissions, the patient suffered an additional relapse. This case highlights the challenges of neonatal thymectomy and adds new insights into the pathogenesis, diagnosis, and management of severe autoimmune enteropathy in pediatric heart transplant recipients.
Liraglutide Attenuates Hepatic Ischemia–Reperfusion Injury by Modulating Macrophage Polarization
Authors: Li Shang-Lin , Wang Zhi-Min , Xu Cong , Che Fu-Heng , Hu Xiao-Fan , Cao Rui , Xie Ya-Nan , Qiu Yang , Shi Hui-Bo , Liu Bin , Dai Chen , Yang Jun
Published: April 2022

Ischemia-reperfusion injury (IRI) is a common complication associated with liver surgery, and macrophages play an important role in hepatic IRI. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog primarily used to treat type 2 diabetes and obesity, regulates intracellular calcium homeostasis and protects the cardiomyocytes from injury; however, its role in hepatic IRI is not yet fully understood. This study aimed to investigate whether liraglutide can protect the liver from IRI and determine the possible underlying mechanisms. Our results showed that liraglutide pretreatment significantly alleviated the liver damage caused by ischemia-reperfusion (I/R), as evidenced by H&E staining, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and TUNEL staining. Furthermore, the levels of inflammatory cytokines elicited by I/R were distinctly suppressed by liraglutide pretreatment, accompanied by significant reduction in TNF-α, IL-1β, and IL-6 levels. Furthermore, pretreatment with liraglutide markedly inhibited macrophage type I (M1) polarization during hepatic IRI, as revealed by the significant reduction in CD68+ levels in Kupffer cells (KCs) detected via flow cytometry. However, the protective effects of liraglutide on hepatic IRI were partly diminished in GLP-1 receptor-knockout (GLP-1R-/-) mice. Furthermore, in an in vitro study, we assessed the role of liraglutide in macrophage polarization by examining the expression profiles of M1 in bone marrow-derived macrophages (BMDMs) from GLP-1R-/- and C57BL/6J mice. Consistent with the results of the in vivo study, liraglutide treatment attenuated the LPS-induced M1 polarization and reduced the expression of M1 markers. However, the inhibitory effect of liraglutide on LPS-induced M1 polarization was largely abolished in BMDMs from GLP-1R-/- mice. Collectively, our study indicates that liraglutide can ameliorate hepatic IRI by inhibiting macrophage polarization towards an inflammatory phenotype via GLP-1R. Its protective effect against liver IRI suggests that liraglutide may serve as a potential drug for the clinical treatment of liver IRI.
Conversion of Waste Corn Biomass to Activated Bio-Char for Applications in Wastewater Treatment
Authors: Karami Shokooh , Papari Sadegh , Berruti Franco
Published: April 2022

This study proposes the conversion of waste corn grains contaminated by deoxynivalenol (also known as vomitoxin), a mycotoxin produced by plant pathogens, into a value-added product. Batches of 500 g of contaminated corn grains were pyrolyzed in a batch reactor by thermal treatment at temperatures up to 500°C with a 15°C/min heating rate and generating condensable vapors, gases and solid bio-char. The bio-char produced was subsequently activated in a furnace at 900°C, using CO2 as an activation agent, at different residence times. The effect of activation residence time on the characteristics of the activated bio-char, varying it from 0.5 to 3 h, was investigated. Characterization tests included BET surface area, SEM, TG-FTIR, pH, and XRD on both bio-char and activated bio-char. BET results illustrated a significant increase of the surface area from 63 to 419 m2g−1 and pore volume from 0.04 to 0.23 cm3g−1 by increasing the activation time from 0.5 to 3 h. SEM images visually confirmed a considerable increase in pore development. The pH significantly increased from 6 to 10 after activation, due to the elimination of acidic functional groups. The proximate analysis showed the stable carbon of the activated char reaching approximately 90 wt%, making it promising for catalyst/adsorbent applications. The adsorption performance of activated bio-char was tested by utilizing three different model molecules with different characteristics: methylene blue, methyl orange, and ibuprofen. Among all activated bio-char samples, activated bio-char with 3 h activation time showed the highest adsorption capacity, with a total adsorption (25 mg/g of activated bio-char) of methylene blue after 5 min. The results showed that the adsorption capacity of the activated bio-char was similar to that of valuable commercial activated carbon.
An Increased Aspartate to Alanine Aminotransferase Ratio Is Associated With a Higher Risk of Cognitive Impairment
Authors: Li Wei , Yue Ling , Sun Lin , Xiao Shifu
Published: April 2022

Background

Recent Alzheimer’s disease (AD) hypotheses implicate that hepatic metabolic disorders might contribute to the disease pathogenesis of AD, but the mechanism remains unclear.

Aims

To investigate whether the elevated aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ratio is associated with future cognitive decline, and to explore the possible mechanisms of liver enzymes affecting cognitive function.

Methods

Three different clinical cohorts were included in the current study, including one cross-sectional study (Cohort 1) and two longitudinal follow-up studies (Cohort 2 and 3). All participants completed a detailed clinical evaluation, neuropsychological tests, and liver enzyme tests. In addition, some of them also underwent structural magnetic resonance imaging (MRI) scans.

Results

Cohort 1 was derived from the CRC2017ZD02 program, including 135 amnestic mild cognitive impairment (aMCI) patients, 22 AD patients, and 319 normal controls. In this cross-sectional study, we found that the AST/ALT ratio was associated with AD (p = 0.014, OR = 1.848, 95%CI: 1.133∼3.012), but not aMCI; Cohort 2 was derived from the Shanghai Brain Health Program. A total of 260 community elderly people with normal cognitive function were included in the study and followed up for 2 years. In this 2-year longitudinal follow-up study, we found that a higher AST/ALT ratio was a risk factor for future development of aMCI (p = 0.014, HR = 1.848, 95%CI: 1.133∼3.021); Cohort 3 was derived from the China longitudinal aging study (CLAS) Program. A total of 94 community elderly people with normal cognitive function were followed up for 7 years, and all of them completed MRI scans. In this 7-year longitudinal follow-up study, we found that a higher AST/ALT ratio was a risk factor for future development of aMCI (p = 0.006, HR = 2.247, 95%CI: 1.248∼4.049), and the AST/ALT ratio was negatively correlated with right hippocampal volume (r = −0.148, p = 0.043).

Conclusion

An increased ratio of AST to ALT is associated with a higher risk of cognitive impairment and may impair cognitive function by affecting hippocampal volume.
A Study of the Efficacy and Safety of Aerobic Exercise Training in Pulmonary Arterial Hypertension (the Saturday Study): Protocol for a Prospective, Randomized, and Controlled Trial
Authors: Jiang Rong , Wang Lan , Yuan Ping , Zhao Qin-Hua , Gong Su-Gang , He Jing , Qiu Hong-Ling , Luo Ci-Jun , Zhang Rui , Shen Ting , Zhan Meng-Yi , Jiang Yu-Mei , Chen Fa-Dong , Liu Jin-Ming , Shen Yu-Qin
Published: April 2022

Background

Patients with pulmonary arterial hypertension (PAH) have reduced exercise capacity and poor quality of life. Exercise-based rehabilitation in PAH results in clinically relevant improvements in exercise capacity and hemodynamics. To clarify the mechanism, we will evaluate the effect of aerobic exercise training rehabilitation on right ventricular (RV) remodeling and function as determined measured by cardiac magnetic resonance imaging (CMR).

Methods

We will conduct a 26-week multicenter randomized controlled trial. Patients on stable and unchanged PAH-targeted medication are randomly assigned (1:1) to the control and training groups. The primary endpoint is the RV stroke volume (RVSV) change from baseline to Week 26, determined by CMR. Comprehensive RV function is also performed using CMR. Other characteristics of the RV and left ventricle, World Health Organization functional class, 6-min walk distance, and N-terminal pro-B-type natriuretic peptide are included in secondary endpoints. We also investigate the proteomic, metabolomic, and transcriptomic changes after exercise training as exploratory endpoints.

Ethics and Dissemination

The study and protocol were approved by the Ethics Committee of Shanghai Pulmonary Hospital (Approved No. of ethics committee: L20-17). The results will be disseminated at medical conferences and in journal publications. All participants will sign written informed consent.

Trial Registration Number

ChiCTR2000031650.
Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines
Authors: Milošević Nenad , Rütter Marie , David Ayelet
Published: April 2022

Endothelial cell adhesion molecules have long been proposed as promising targets in many pathologies. Despite promising preclinical data, several efforts to develop small molecule inhibitors or monoclonal antibodies (mAbs) against cell adhesion molecules (CAMs) ended in clinical-stage failure. In parallel, many well-validated approaches for targeting CAMs with nanomedicine (NM) were reported over the years. A wide range of potential applications has been demonstrated in various preclinical studies, from drug delivery to the tumor vasculature, imaging of the inflamed endothelium, or blocking immune cells infiltration. However, no NM drug candidate emerged further into clinical development. In this review, we will summarize the most advanced examples of CAM-targeted NMs and juxtapose them with known traditional drugs against CAMs, in an attempt to identify important translational hurdles. Most importantly, we will summarize the proposed strategies to enhance endothelial CAM targeting by NMs, in an attempt to offer a catalog of tools for further development.