bluuebunny/crossref_metadata_2025 huggingface dataset:
Sistem Informasi Pengolahan Nilai Siswa Berbasis Web Pada SMP Al -Washliyah
Authors: Nurhanifa Cici , Puspasari Ratih
Published: June 2023

Sistem informasi pengolahan data nilai siswa merupakan sistem yang memberikan informasi berhubungan laporan aktivitas siswa. Permasalahan yang sering terjadi pada era pengolahan data nilai ialah pengolahan yang masih konservatif, yaitu guru mata pelajaran individual menyingkat hasil belajar siswa pada kertas kemudian memberikan kertas tersebut atau akumulasi dari kelas. guru dan di kelas. guru menulis ulang hasil ringkasan berisi format halaman guru pada rapor tiap-tiap siswa. Karena itu, membutuhkan waktu lama untuk menetapkan nilai, terutama untuk mendapatkan nilai akhir. Guru kelas telat mengisi rapor, karena guru kelas harus menunggu semua guru memberikan nilai tiap-tiap mata pelajaran, sedangkan setiap guru mengajar tidak hanya satu mata pelajaran tetapi beberapa mata pelajaran, melebihi guru dan tidak selesai tepat waktu
Perancangan Alat Pelindung Diri Topi Sebo Pada Welder dan Fitter Menggunakan Metode Ergonomic Function Deployment (EFD) di PT XYZ
Authors: Safi’i Muhammad , Marwan
Published: June 2023

Untuk meningkatkan kualitas dan kuantitas hasil kerjanya, diperlukan pemenuhan keamanan dan kenyaman dari perusahaan untuk para pekerjanya terutama welder dan fitter. Terdapat banyak kendala yang menyebabkan welder dan fitter sering mengeluh terhadap kondisi kerja mereka seperti mereka sering mendapat luka percikan bunga api las pada leher mereka sehingga hasil kerja mereka menjadi kurang optimal oleh karena itu dikembangkan alat pelindung diri yaitu topi sebo yang dirancang dengan menggunakan metode Ergonomic Function Deployment (EFD) dan dalam perancangannya digunakan keinginan konsumen (voice of customers) guna untuk melindungi welder dan fitter dalam melakukan pekerjaannya. Adapun hal-hal yang diinginkan konsumen dalam hal ini welder dan fitter berdasarkan kuisioner yang peneliti berikan, mereka menginginkan topi sebo yang dapat melindungi dari percikan api las, topi sebo tersebut memiliki harga yang ekonomis, memiliki desain yg ergonomis, tahan lama, bisa dicuci kembali, warna yang menarik, mudah di gunakan, dan topi sebo tersebut dapat digunakan di semua kondisi. Dari 30 responden 74,4% menyatakan bahwa rancangan produk topi sebo yang dirancang dengan metode EFD sangat bagus, 19,3% menyatakan rancangan tersebut lebih bagus, 5,7% menyatakan bagus, 0,4% menyatakan jelek dan 0% yang menyatakan sangat jelek.
Pengaruh Kepuasan Konsumen Terhadap Kualitas Pelayanan Instalasi Saluran Air PT.SHL
Authors: L toruan Vernando , Ismail
Published: June 2023

Penelitian ini bertujuan untuk mengetahui pengaruh kualitas pelayanan terhadap kepuasan pelanggan PT. SHL. Dalam penelitian ini kualitas layanan meliputi bukti langsung, kehandalan, daya tanggap, jaminan, dan empati. Penelitian ini akan mengkaji dampak kualitas pelayanan terhadap kepuasan pelanggan baik secara simultan maupun sebagian. Besar sampel dalam penelitian ini adalah 30 orang, dan besar sampel penelitian ini dihitung dengan menggunakan rumus slovin. Teknik pengumpulan data dilakukan dengan menggunakan kuesioner dan instrumen penelitian menggunakan skala likert. Metode analisis yang digunakan dalam penelitian ini adalah aplikasi SPSS 26 untuk analisis regresi linier berganda. Hasil penelitian (uji t) menunjukkan bahwa kualitas pelayanan berpengaruh signifikan terhadap kepuasan pelanggan. Nilai signifikansi untuk masing-masing variabel kurang dari 0,05. Hasil pengujian koefisien determinasi menghasilkan R Square sebesar 0,953. Hal ini menunjukkan 95,3 % variabel kepuasan konsumen dipengaruhi oleh variabel kualitas pelayanan, sedangkan 4,7% dipengaruhi oleh variabel lain yang tidak diteliti dalam penelitian ini.
Analisis Distribusi Persediaan Produk Dengan Metode Distribution Requeirement Planning (DRP) Di PT. XYZ
Authors: Dumato Sihotang Ramot R Sihotang , Ismail
Published: June 2023

Dalam suatu perusahaan produk,bagian akhir suatu proses produksi adalah pendistribusian produk yang hingga akhirnya barang sampai ke tangan tangan konsumen.Tetapi permasalahan yang sering terjadi saat barang yang sudah keluar dari pabrik yaitu saat pendistribusian.PT.XYZ memiliki masalah distribusi,karena memiliki agen distribusi yang besar dan tersebar di beberapa wilayah.Dalam Pendistribusian barang sering terjadi keterlambatan barang,dan jumlah yang tidak sesuai pesanan,sehingga menimbulakan biaya untuk mengatasi masalah dalam perusahaan tersebut. Metode yang digunakan adalah Distribution Requirement Planning (DRP) dengan metode Lot Sizeing lot for lot (LFL), Economic Order Quantity (EOQ),Period Order Quantity (POQ),Pengaruh optimasi perencanaan pendistribusian persediaan bahan baku karet rumb rubber di PT XYZ, terhadap nilai persentase biaya adalah 22%. Jadi dapat diketahui bahwa metode DRP sangat berpengaruh meminumkan total biaya yang berhubungan dengan aktivitas distribusi (biaya penyimpanan dan biaya distribusi) dengan efektif dan efisien.
A Review on the Physicochemical and Biological Aspects of the Chitosan Antifungal Activity in Agricultural Applications
Authors: Velásquez Cristóbal Lárez , Avelizapa Luz Rojas
Published: June 2023

The antifungal activity of the chitosan biopolymer has been extensively studied for several decades. However, the mechanisms of action associated with this process have not been fully clarified yet. To a large extent, this situation is due to the lack of systematization with which, in general terms, the subject has been approached. However, it seems to have begun to change in recent years with the appearance of several papers reviewing the accumulated knowledge on the beneficial effects shown by chitosan in agricultural applications and putting forward it in a more systematic mode. In this work, the most relevant mechanisms of action proposed for chitosan regarding its antifungal activity will be briefly presented, i.e., disruption and changes in the fungal plasma membrane, alteration of gene expression, inhibition of RNA and protein synthesis, Ca2+ channel blocker, to then address the main factors that influence this antifungal activity, observed mainly in studies focused on phytopathogenic species, which have been grouped into three main blocks: those related exclusively to the chitosan molecules, those associated to the fungal itself and those having to do with the environment where the processes take place. Additionally, a brief section addressing some possibilities on which future studies on this topic should focus is also included.
Editorial - In the Kingdom of the Blind, the One-Eyed Man is King: The Case for The International Journal of Statistics in Medical Research
Authors: Biondi-Zoccai Giuseppe
Published: June 2023

International Journal of Criminology and Sociology, Volume 2 Number 1, Editorial
El mobile learning en el aprendizaje del inglés en la Educación Superior: una revisión sistemática
Authors: Gobantes Andrea
Published: June 2023

Learning English as a foreign language is crucial to cope in a globalized society. Moreover, technological advances along with the integration of ICT into education in the last decades have enhanced the teaching-learning process thanks to the emergence of new tools and modes of teaching, such as mobile learning.
To ascertain whether mobile learning benefits the process of learning English as a foreign language, a systematic review of qualitative design was conducted. During the research process, 38 articles that met the eligibility criteria were retrieved and thus, they were classified depending on their object of study. This paper concludes that mobile learning fosters the development of the communicative competences (oral comprehension, oral production, written comprehension and written production) to learn English as a foreign language at Higher Education. Similarly, positive results have also been noted regarding the linguistic competences of vocabulary and pronunciation to learn English at Higher Education. Nevertheless, greater disparity of results is found in relation to grammar learning. Finally, a change of research tendency is noted in the last two decades regarding English learning through m-learning given that oral production has gone from being the third most studied communicative competence to be the most analysed, followed by vocabulary learning.

Aprender inglés como lengua extranjera es esencial para desenvolverse en una sociedad globalizada. Además, los avances tecnológicos y la introducción de las TIC en el campo de la educación durante las últimas décadas han permitido mejorar el proceso de enseñanza-aprendizaje gracias a creación de nuevas herramientas y modalidades de enseñanza, como por ejemplo el aprendizaje móvil (mobile learning).
Para comprobar si el mobile learning favorece el aprendizaje del inglés se llevó a cabo una revisión sistemática de corte cualitativo. Durante la búsqueda de estudios, se recuperaron 38 que cumplieron los criterios de elegibilidad y se clasificaron de acuerdo al objeto de estudio. En este trabajo se concluye que el mobile learning favorece el desarrollo de las competencias comunicativas (comprensión oral, producción oral, comprensión escrita y producción escrita) para aprender inglés como lengua extranjera en enseñanzas superiores. Del mismo modo, también se evidencian resultados positivos para el desarrollo de las competencias lingüísticas de vocabulario y pronunciación para aprender inglés en Educación Superior. Sin embargo, se encuentra una mayor disparidad de resultados en relación al aprendizaje de la gramática. Por último, se señala un cambio de tendencia de las competencias analizadas en las últimas dos décadas en relación al aprendizaje del inglés a través del mobile learning puesto que la producción oral ha pasado de ser la tercera competencia comunicativa a ser la competencia más estudiada, seguida del aprendizaje de vocabulario.
Periodic, nonperiodic, and chaotic solutions for a class of difference equations with negative feedback
Authors: Kennedy Benjamin B.
Published: June 2023

We study the scalar difference equation \[x(k+1) = x(k) + \frac{f(x(k-N))}{N},\] where \(f\) is nonincreasing with negative feedback. This equation is a discretization of the well-studied differential delay equation \[x'(t) = f(x(t-1)).\] We examine explicit families of such equations for which we can find, for infinitely many values of $ and appropriate parameter values, various dynamical behaviors including periodic solutions with large numbers of sign changes per minimal period, solutions that do not converge to periodic solutions, and chaos. We contrast these behaviors with the dynamics of the limiting differential equation. Our primary tool is the analysis of return maps for the difference equations that are conjugate to continuous self-maps of the circle.
A cautionary comment on the morphological status of inclusive –e in Spanish
Authors: Muñoz Pérez Carlos
Published: June 2023

This squib discusses several alternative grammatical treatments for inclusive -e in Spanish. It shows that the available data does not allow to prefer or disregard any of the potential proposals.
Differential object marking in inanimate objects in Spanish
Authors: Camacho Rafael
Published: June 2023

The aim of this paper is to explain the differential object marking (DOM) of inanimate objects in Spanish. Generally, animate objects in Spanish are marked with an A morpheme; however, it is possible for the A-marker to appear also with inanimate objects in specific circumstances. In this article, I defend the idea that a lexical feature of the verb (the presupposition of existence) must be licensed with the organizing node that dominates the specificity features. V inherits this organizing node from v. The analysis will be done using mainly two theoretical tools: the feature geometry of Harley & Ritter (2002) and Chomsky's (2013, 2015) labeling theory.
Retrospective study of transcriptomic profiling identifies Thai triple-negative breast cancer patients who may benefit from immune checkpoint and PARP inhibitors
Authors: Suntiparpluacha Monthira , Chanthercrob Jantappapa , Sa-nguanraksa Doonyapat , Sitthikornpaiboon Juthamas , Chaiboonchoe Amphun , Kueanjinda Patipark , Jinawath Natini , Sampattavanich Somponnat
Published: June 2023

Background

Triple-negative breast cancer (TNBC) is a rare and aggressive breast cancer subtype. Unlike the estrogen receptor-positive subtype, whose recurrence risk can be predicted by gene expression-based signature, TNBC is more heterogeneous, with diverse drug sensitivity levels to standard regimens. This study explored the benefit of gene expression-based profiling for classifying the molecular subtypes of Thai TNBC patients.

Methods

The nCounter-based Breast 360 gene expression was used to classify Thai TNBC retrospective cohort subgroups. Their expression profiles were then compared against the previously established TNBC classification system. The differential characteristics of the tumor microenvironment and DNA damage repair signatures across subgroups were also explored.

Results

Thai TNBC cohort could be classified into four main subgroups, corresponding to the LAR, BL-2, and M subtypes based on Lehmann’s TNBC classification. The PAM50 gene set classified most samples as basal-like subtypes except for Group 1. Group 1 exhibited similar enrichment of the metabolic and hormone response pathways to the LAR subtype. Group 2 shared pathway activation with the BL-2 subtype. Group 3 showed an increase in the EMT pathway, similar to the M subtype. Group 4 showed no correlation with Lehmann’s TNBC. The tumor microenvironment (TME) analysis showed high TME cell abundance with increased expression of immune blockade genes in Group 2. Group 4 exhibited low TME cell abundance and reduced immune blockade gene expressions. We also observed distinct signatures of the DNA double-strand break repair genes in Group 1.

Conclusions

Our study reported unique characteristics between the four TNBC subgroups and showed the potential use of immune checkpoint and PARP inhibitors in subsets of Thai TNBC patients. Our findings warrant further clinical investigation to validate TNBC’s sensitivity to these regimens.
Amor, risa y mujeres: analizando el rol del cuidado y las afecciones en prácticas performativas
Authors: Inostroza Bravo Valentina , Hono Olmos Francisca
Published: June 2023

No presenta resumen
Matematik Öğretmen Adaylarının Prizma ve Silindire Yönelik Kavram İmajlarının Tanımları, Çizimleri ve Gruplandırma Becerileri Kapsamında İncelenmesi
Authors: ALİUSTAOĞLU Feyza
Published: June 2023

Bu araştırmada ilköğretim matematik öğretmen adaylarının prizma ve silindire yönelik kavram imajlarını ortaya çıkarmak amaçlanmıştır. Bu amaç doğrultusunda öğretmen adaylarının bu geometrik cisimlere yönelik tanımları, farklı çizimleri ve verilen geometrik cisimleri gruplandırma biçimleri incelenmiştir. Araştırma durum çalışması modeline dayalı olarak yürütülmüştür. Araştırmanın çalışma grubunu Türkiye’nin kuzeyinde bulunan bir devlet üniversitesinin Eğitim Fakültesi İlköğretim Matematik Öğretmenliği Bölümünde birinci sınıf düzeyinde öğrenim gören 45 öğretmen adayı oluşturmaktadır. Öncelikle uygun örnekleme yöntemi kullanılarak belirlenen öğretmen adaylarına silindir ve prizmaya yönelik tanımlama, çizim yapma ve gruplama becerilerini içeren geometrik cisimler bilgi testi uygulanmıştır. Ardından maksimum çeşitlilik örneklemesi yöntemine dayalı olarak öğretmen adaylarının verdikleri cevapların incelenmesi sonucunda 6 öğretmen adayı ile görüşmeler gerçekleştirilmiştir. Verilerin analizi içerik analizi tekniğine dayalı olarak gerçekleştirilmiştir. Görüşme verilerinin analizinde ise betimsel analiz tekniği kullanılmıştır. Araştırmadan elde edilen sonuçlar öğretmen adaylarının tanımları, çizimleri ve gruplandırma biçimleri başlıkları altında sunulmuştur. Araştırma sonucunda öğretmen adaylarının silindir ve prizma tanımlarının tam olarak yeterli olmadığı, bu geometrik cisimlere yönelik kritik özellikleri ayırt etmekte güçlük yaşadıkları bulunmuştur. Kavram imajları genellikle silindir için dairesel tabanlı ve prizma için çokgen tabanlı ve dik cisimler şeklindedir. Çizimlerinde genellikle prototif algıya dayalı çizim yapmışlar, gruplandırmada da prototif örnekleri ayırt etmekte zorlanmamışlar ancak prototif olmayan örnekleri ayırt etmekte zorlanmışlardır. Öğretmen adaylarının kavram imajlarının kavram tanımlarına göre daha baskın olduğu görülmüştür. Ayrıca matematiksel dili kullanmada hatalar yaptıkları ve konu ile ilgili alan bilgilerinde de eksikler olduğu tespit edilmiştir. Silindir ve prizma arasındaki hiyerarşik ilişki düşündüğünde öğretmen adaylarının genellikle bu cisimleri ayrık kümeler olarak düşünmekle birlikte farklı fikirlere sahip olduğu sonucuna ulaşılmıştır. Araştırmadan elde edilen sonuçlara dayalı olarak çeşitli öneriler getirilmiştir.
Qualitative Analysis of the Right Plantar Dermatoglyphic Configurations in Himachal Pradesh: A Dimorphic Study
Authors: Ohri Meenal , Bedi Minu , Chaturvedi Harish
Published: June 2023

Introduction: Dermatoglyphics is defined as the study of the configurations on the plantar aspect of the feet and the palmar aspect of the hands. It is a well established fact that these epidermal configurations are distinct for each and every individual. Aim: To study and analyse the plantar dermatoglyphic patterns on the right sole of the individuals of Himachal Pradesh and to know its implication in gender determination. Material and Methods: This cross-sectional study was conducted in the Department of Anatomy, Adesh Institute of Medical Sciences, Bathinda, Punjab, India, and the data was collected over a period of one year (May 2021 to May 2022). The sole dermatoglyphic prints of 400 individuals (200 males and 200 females) of the age group 18-45 years without any known medical conditions were analysed for the dermatoglyphic patterns visualised in the Hallucal/Thenar/ First Interdigital Area (Rt Th/H/ID1), Second Interdigital Area (Rt ID2), Third Interdigital Area (Rt ID3), Fouth Interdigital Area (Rt ID4), Hypothenar Distal Area (Rt HTD), Hypothenar Proximal Area (Rt HTP) and the Calcar Area (Rt C) of the right sole. The findings thus obtained were then subjected to Chi-square test using the Statistical Package for the Social Sciences (SPSS) version 21.0 software. Results: The mean age of the subjects included in the study was 29±4 years and 16±7 years for 200 Himachali males and 200 Himachali females, respectively. The study showed that there was indeed an association between the right plantar dermatoglyphic patterns and the sex of the people belonging to Himachal Pradesh, India. The results suggest that the distribution of the dermatoglyphic patterns on Rt Th/H/ID1 of the females was significantly different from the males (p-value <0.05). On the Rt ID2, Rt ID3 and Rt ID4, the differences observed between the females and males were highly significant (p-value <0.001) whereas on the Rt HTD, Rt HTP and the Rt C, all the males and females depicted a lack of pattern. Conclusion: The results of this investigation suggest that there exist some significant differences between the male and female subjects of Himachali population. The plantar dermatoglyphic patterns could therefore be utilised as an important tool to determine the gender of an individual in forensic and medico-legal aspects as well as to determine the relationship of an individual to an ethnic group based in different geographical areas.
Statistical Study of Rainfall Variations Across Different Districts of Bundelkhand Region, India
Authors: Singh Priya , Gautam Shweta , Patel Anil , Singh Balwant
Published: June 2023

The Bundelkhand region, one of the most vulnerable locations in central India, is prone to severe drought and crop failure attributed to annual rainfall fluctuation. In this study, basic statistics were utilized to determine the variances in rainfall across different districts in the Bundelkhand zone for 30 years (1987-2016) The average annual rainfall was found to be maximum for Damoh district (1169.24 mm) followed by Sagar district (1163.04 mm), Panna district (1118.79 mm), whereas it was minimum for Jalaun district (774.91 mm) followed by Datia district (841.61 mm), Hamirpur district (849.30 mm). In this study period in the year 2010 received low annual rainfall. The average seasonal rainfall was found to be maximum for Sagar district (1075.52 mm) followed by Damoh district (1073.40 mm), Panna district (1008.74 mm) whereas was minimum for Jalaun district (701.11 mm) followed by Datia district (769.1 mm). In this 30 year 1990 real received low seasonal rainfall. This research demonstrates the rainfall pattern over the study region and indicates susceptible locations that are more likely to face water stress as a result of rainfall variability.
Exploring the Narrative Spaces of Change in Jejak Warna: Cerita tentang Perubahan (2019) Web Series
Authors: Chusna Aidatul , Irawanto Budi , Arymami Dian
Published: June 2023

Jejak Warna: Cerita tentang Perubahan (Color Trail: A Story of Change) web series talks about a man named Arya who is stuck with his monotonous life and memory of his ex-girlfriend. His life changes when he meets Kinar – his new colleague.  This study explores how the narrative space conveys the idea of change by analysing the mise-en-scène elements of the web series. The result shows the depiction of spaces which change from spaces that bind the protagonist in his dull routine and memory to a space that liberates and offers him new life and adventure. The change is strengthened by the changing nuances of spaces depicted through composition and lighting, sound (dialogue and music), and the character's expression and movement within the spaces.
The Construction of Masculinity in Layangan Putus
Authors: Widodo Mercillia , Mochtar Jenny
Published: June 2023

A phenomenal sinetron, Layangan Putus, has enraptured and polarized Indonesian audiences when it was aired. With its accessibility and popularity, sinetron is a powerful tool of the construction of identity and is a source of potent, though sometimes invisible, ideologies. The construction of masculinity is evident through four social forms of images, myths, discourses and practices proposed by Reeser (2010). The main character, Aris, is portrayed as the ideal man with his capability to provide and attract women. This notion is in full contrast with other male characters portrayed as ‘failed’ or mediocre, and whose weaknesses only showcase Aris’ dominance. The sinetron depicts the reality as Aris’ qualities are encouraged and even catapulted as the epitome of masculinity. On the other hand, his loss of masculinity in the end serves as a critique towards the idealized masuline man. This suggests the double nature of gender representations in mass media.
Representações culturais de jovens em conflito com a lei
Authors: Vasconcelos Teixeira Débora Isabele , Chotolli Wesley Piante
Published: June 2023

Considerando a questão das representações, vivências e trajetórias artísticas-culturais, objetiva-se compreender a trajetória de jovens em conflito com a lei e suas relações com a estética e a arte em um município do interior paulista. Para tanto, a pesquisa apresenta abordagem qualitativa e foi realizada entrevistas semiestruturadas com adolescentes no cumprimento de medida socioeducativa em meio aberto, acompanhada de um projeto desenvolvido pelo Centro de Referência Especializado da Assistência Social (Creas) no município de Penápolis-SP. Desse modo, a partir dos relatos dos sujeitos e suas relações com os espaços municipais disponíveis, conclui-se que são poucas as representações artístico-culturais em suas trajetórias e a arte enquanto direito estruturante da juventude, precisa ser fomentada como parte potente no processo educacional, socioeducativo e de transformação das relações sociais.
Cerebrospinal Fluid Venous Fistula Imaging with Ultrahigh-Resolution Cone-Beam Computed Tomography
Authors: Lützen Niklas , Beck Jürgen , Urbach Horst
Published: June 2023

This case report describes a cerebrospinal fluid venous fistula imaged with ultrahigh-resolution cone-beam computed tomography.
Stabilization of α‐phase FAPbI3 via Buffering Interfacial Region for Efficient p–i–n Perovskite Solar Cells
Authors: Huang Yulan , Wang Bingzhe , Liu Tanghao , Li Dongyang , Zhang Yujie , Zhang Tianqi , Yao Xiyu , Wang Yun , Amini Abbas , Cai Yongqing , Xu Baomin , Tang Zikang , Xing Guichuan , Cheng Chun
Published: June 2023

Formamidinium lead triiodide (FAPbI3) with an ideal bandgap and good thermal stability has received wide attention and achieved a record efficiency of 26% in n–i–p (regular) perovskite solar cells (PSCs). However, imperfect FAPbI3 formation on the typical hole transport layer (HTL), high interfacial trap‐state density, and unfavorable energy alignment between the HTL and FAPbI3 result in the inferior photovoltaic performance of p–i–n (inverted) PSCs with FAPbI3 absorber. Herein, the α‐phase FAPbI3 is stabilized by constructing a buffer interface region between the NiOx HTL and FAPbI3, which not only diminishes NiOx/FAPbI3 interfacial reactions and defects but also facilitates carrier transport. Upon the construction of a buffer interface region, FAPbI3 inverted PSC exhibits a high‐power conversion efficiency of 23.56% (certified 22.58%) and excellent stability, retaining 90.7% of its initial efficiency after heating at 80 °C for 1000 h and 84.6% of the initial efficiency after operating at the maximum power point under continuous illumination for 1100 h. Besides, as a light‐emitting diode device, the FAPbI3 inverted PSC can be directly lit with an external quantum efficiency of 1.36%. This study provides a unique and efficient strategy to advance the application of α‐phase FAPbI3 in inverted PSCs.
Sm/Co‐Doped Silica‐Based Nanozymes Reprogram Tumor Microenvironment for ATP‐Inhibited Tumor Therapy
Authors: Li Siyi , Ding He , Chang Jinghu , Liu Shikai , Dong Shuming , Zyuzin Mikhail V. , Timin Alexander S. , Feng Lili , He Fei , Gai Shili , Yang Piaoping
Published: June 2023

Current applications of multifunctional nanozymes for reprogramming the redox homeostasis of the tumor microenvironment (TME) have been severely confronted with low catalytic activity and the ambiguity of active sites of nanozymes, as well as the stress resistance from the rigorous physical environment of tumor cells. Herein, the Sm/Co‐doped mesoporous silica with 3PO‐loaded nanozymes (denoted as mSC‐3PO) are rationally constructed for simultaneously inhibiting energy production by adenosine triphosphate (ATP) inhibitor 3PO and reprogramming TME by multiactivities of nanozymes with photothermal effect assist, i.e., enhanced peroxidase‐like, catalase‐like activity, and glutathione peroxidase‐like activities, facilitating reactive oxygen species (ROS) generation, promoting oxygen content, and restraining the over‐expressed glutathione. Through the optimal regulation of nanometric size and doping ratio, the fabricated superparamagnetic mSC‐3PO enables the excellent exposure of active sites and avoids agglomeration owing to the large specific surface and mesoporous structure, thus providing adequate Sm/Co‐doped active sites and enough spatial distribution. The constructed Sm/Co centers both participate in the simulated biological enzyme reactions and carry out the double‐center catalytic process (Sm3+and Co3+/Co2+). Significantly, as the inhibitor of glycolysis, 3PO can reduce the ATP flow by cutting down the energy transform, thereby inhibiting tumor angiogenesis and assisting ROS to promote the early withering of tumor cells. In addition, the considerable near‐infrared (NIR) light absorption of mSC‐3PO can adapt to NIR excitable photothermal treatment therapy and photoexcitation‐promoted enzymatic reactions. Taken together, this work presents a typical therapeutic paradigm of multifunctional nanozymes that simultaneously reprograms TME and promotes tumor cell apoptosis with photothermal assistance.
Controllable Regulation of Ag2S Quantum‐Dot‐Mediated Protein Nanoassemblies for Imaging‐Guided Synergistic PDT/PTT/Chemotherapy against Hypoxic Tumor
Authors: He Mengjie , Cheng Ziyi , Wang Zhenkai , Li Min , Liang Huixian , Liu Heng , Yu Lijuan , Zhao Linlu , Yu Fabiao
Published: June 2023

The combination of phototherapy and chemotherapy holds great potential for cancer treatment, while hypoxia in tumor as well as unexpected drug release largely restricts anticancer therapy. Inspired by the natural intelligence, herein, for the first time, a “bottom‐up” protein self‐assembly strategy mediated by near‐infrared (NIR) quantum dots (QDs) with multicharged electrostatic interactions is presented to develop a tumor microenvironment (TME)‐responsive theranostic nanoplatform for imaging‐guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT)/chemotherapy. Catalase (CAT) possesses diverse surface charge distribution under different pH conditions. After modification by chlorin e6 (Ce6), the formulated CAT–Ce6 with patchy negative charges can be assembled with NIR Ag2S QDs by regulating their electrostatic interactions, allowing for effective incorporation of specific anticancer drug oxaliplatin (Oxa). Such Ag2S@CAT–Ce6@Oxa nanosystems are able to visualize nanoparticle (NP) accumulation to guide subsequent phototherapy, together with significant alleviation of tumor hypoxia to further enhance PDT. Moreover, the acidic TME triggers controllable disassembly through weakening the CAT surface charge to disrupt electrostatic interactions, allowing for sustained drug release. Both in vitro and in vivo results demonstrate remarkable inhibition of colorectal tumor growth with a synergistic effect. Overall, this multicharged electrostatic protein self‐assembly strategy provides a versatile platform for realizing TME‐specific theranostics with high efficiency and safety, promising for clinical translation.
How to GIWAXS: Grazing Incidence Wide Angle X‐Ray Scattering Applied to Metal Halide Perovskite Thin Films
Authors: Steele Julian A. , Solano Eduardo , Hardy David , Dayton Damara , Ladd Dylan , White Keith , Chen Peng , Hou Jingwei , Huang Haowei , Saha Rafikul Ali , Wang Lianzhou , Gao Feng , Hofkens Johan , Roeffaers Maarten B. J. , Chernyshov Dmitry , Toney Michael F.
Published: June 2023

The frequency of reports utilizing synchrotron‐based grazing incident wide angle X‐ray scattering (GIWAXS) to study metal halide perovskite thin films has exploded recently, as this technique has proven invaluable for understanding several structure‐property relationships that fundamentally limit optoelectronic performance. The GIWAXS geometry and temporal resolution are also inherently compatible with in situ and operando setups (including ISOS protocols), and a relatively large halide perovskite research community has deployed GIWAXS to unravel important kinetic and dynamic features in these materials. Considering its rising popularity, the aim here is to accelerate the required learning curve for new experimentalists by clearly detailing the underlying analytical concepts which can be leveraged to maximize GIWAXS studies of polycrystalline thin films and devices. Motivated by the vast range of measurement conditions offered, together with the wide variety of compositions and structural motifs available (i.e., from single‐crystal and polycrystalline systems, to quantum dots and layered superlatices), a comprehensive framework for conducting effective GIWAXS experiments is outlined for different purposes. It is anticipated that providing a clear perspective for this topic will help elevate the quality of future GIWAXS studies—which have become routine—and provide the impetus required to develop novel GIWAXS approaches to resolve unsettled scientific questions.
Identification of complications requiring interventions after gastrointestinal cancer surgery from real‐world data: An external validation study
Authors: Kinoshita Hiromitsu , Nishigori Tatsuto , Kunisawa Susumu , Hida Koya , Hosogi Hisahiro , Inamoto Susumu , Hata Hiroaki , Matsusue Ryo , Imanaka Yuichi , Obama Kazutaka , Matsumura Yumi
Published: June 2023

Background

Recently, real‐world data have been recognized to have a significant role for research and quality improvement worldwide. The decision on the existence or nonexistence of postoperative complications is complex in clinical practice. This multicenter validation study aimed to evaluate the accuracy of identification of patients who underwent gastrointestinal (GI) cancer surgery and extraction of postoperative complications from Japanese administrative claims data.

Methods

We compared data extracted from both the Diagnosis Procedure Combination (DPC) and chart review of patients who underwent GI cancer surgery from April 2016 to March 2019. Using data of 658 patients at Kyoto University Hospital, we developed algorithms for the extraction of patients and postoperative complications requiring interventions, which included an invasive procedure, reoperation, mechanical ventilation, hemodialysis, intensive care unit management, and in‐hospital mortality. The accuracy of the algorithms was externally validated using the data of 1708 patients at two other hospitals.

Results

In the overall validation set, 1694 of 1708 eligible patients were correctly extracted by DPC (sensitivity 0.992 and positive predictive value 0.992). All postoperative complications requiring interventions had a sensitivity of >0.798 and a specificity of almost 1.000. The overall sensitivity and specificity of Clavien–Dindo ≥grade IIIb complications was 1.000 and 0.995, respectively.

Conclusion

Patients undergoing GI cancer surgery and postoperative complications requiring interventions can be accurately identified using the real‐world data. This multicenter external validation study may contribute to future research on hospital quality improvement or to a large‐scale comparison study among nationwide hospitals using real‐world data.
PUF60‐related developmental disorder: A case series and phenotypic analysis of 10 additional patients with monoallelic PUF60 variants
Authors: Grimes H. , Ansari M. , Ashraf T. , Cueto‐González Anna Mª. , Calder A. , Day M. , Fernandez Alvarez P. , Foster A. , Lahiri N. , Repetto G. M. , Scurr I. , Varghese V. , Low Karen J.
Published: June 2023

PUF60‐related developmental disorder (also referred to as Verheij syndrome), resulting from haploinsufficiency of PUF60, is associated with multiple congenital anomalies affecting a wide range of body systems. These anomalies include ophthalmic coloboma, and congenital anomalies of the heart, kidney, and musculoskeletal system. Behavioral and intellectual difficulties are also observed. While less common than other features associated with PUF60‐related developmental disorder, for instance hearing impairment and short stature, identification of specific anomalies such as ophthalmic coloboma can aid with diagnostic identification given the limited spectrum of genes linked with this feature. We describe 10 patients with PUF60 gene variants, bringing the total number reported in the literature, to varying levels of details, to 56 patients. Patients were recruited both via locally based exome sequencing from international sites and from the DDD study in the United Kingdom. Eight of the variants reported were novel PUF60 variants. The addition of a further patient with a reported c449‐457del variant to the existing literature highlights this as a recurrent variant. One variant was inherited from an affected parent. This is the first example in the literature of an inherited variant resulting in PUF60‐related developmental disorder. Two patients (20%) were reported to have a renal anomaly consistent with 22% of cases in previously reported literature. Two patients received specialist endocrine treatment. More commonly observed were clinical features such as: cardiac anomalies (40%), ocular abnormalities (70%), intellectual disability (60%), and skeletal abnormalities (80%). Facial features did not demonstrate a recognizable gestalt. Of note, but remaining of unclear causality, we describe a single pediatric patient with pineoblastoma. We recommend that stature and pubertal progress should be monitored in PUF60‐related developmental disorder with a low threshold for endocrine investigations as hormone therapy may be indicated. Our study reports an inherited case with PUF60‐related developmental disorder which has important genetic counseling implications for families.
Longitudinal amyloid and tau PET imaging in Alzheimer's disease: A systematic review of methodologies and factors affecting quantification
Authors: Bollack Ariane , Pemberton Hugh G. , Collij Lyduine E. , Markiewicz Pawel , Cash David M. , Farrar Gill , Barkhof Frederik ,   on behalf on the AMYPAD consortium
Published: June 2023

Deposition of
amyloid and tau pathology can be quantified in vivo using positron emission tomography (PET). Accurate longitudinal measurements of accumulation from these images are critical for characterizing the start and spread of the disease. However, these measurements are challenging; precision and accuracy can be affected substantially by various sources of errors and variability. This review, supported by a systematic search of the literature, summarizes the current design and methodologies of longitudinal PET studies. Intrinsic, biological causes of variability of the Alzheimer's disease (AD) protein load over time are then detailed. Technical factors contributing to longitudinal PET measurement uncertainty are highlighted, followed by suggestions for mitigating these factors, including possible techniques that leverage shared information between serial scans. Controlling for intrinsic variability and reducing measurement uncertainty in longitudinal PET pipelines will provide more accurate and precise markers of disease evolution, improve clinical trial design, and aid therapy response monitoring.
Longitudinal Alterations of Cerebral Blood Flow in High‐Contact Sports
Authors: Karimpoor Mahta , Georgiadis Marios , Zhao Moss Y. , Goubran Maged , Moein Taghavi Hossein , Mills Brian D. , Tran Dean , Mouchawar Nicole , Sami Sohrab , Wintermark Max , Grant Gerald , Camarillo David B. , Moseley Michael E. , Zaharchuk Greg , Zeineh Michael M.
Published: June 2023

Objective

Repetitive head trauma is common in high‐contact sports. Cerebral blood flow (CBF) can measure changes in brain perfusion that could indicate injury. Longitudinal studies with a control group are necessary to account for interindividual and developmental effects. We investigated whether exposure to head impacts causes longitudinal CBF changes.

Methods

We prospectively studied 63 American football (high‐contact cohort) and 34 volleyball (low‐contact controls) male collegiate athletes, tracking CBF using 3D pseudocontinuous arterial spin labeling magnetic resonance imaging for up to 4 years. Regional relative CBF (rCBF, normalized to cerebellar CBF) was computed after co‐registering to T1‐weighted images. A linear mixed effects model assessed the relationship of rCBF to sport, time, and their interaction. Within football players, we modeled rCBF against position‐based head impact risk and baseline Standardized Concussion Assessment Tool score. Additionally, we evaluated early (1–5 days) and delayed (3–6 months) post‐concussion rCBF changes (in‐study concussion).

Results

Supratentorial gray matter rCBF declined in football compared with volleyball (sport‐time interaction p = 0.012), with a strong effect in the parietal lobe (p = 0.002). Football players with higher position‐based impact‐risk had lower occipital rCBF over time (interaction p = 0.005), whereas players with lower baseline Standardized Concussion Assessment Tool score (worse performance) had relatively decreased rCBF in the cingulate‐insula over time (interaction effect p = 0.007). Both cohorts showed a left–right rCBF asymmetry that decreased over time. Football players with an in‐study concussion showed an early increase in occipital lobe rCBF (p = 0.0166).

Interpretation

These results suggest head impacts may result in an early increase in rCBF, but cumulatively a long‐term decrease in rCBF. ANN NEUROL 2023;94:457–469
Liquid Metal‐Promoted Graphene Oxide Supramolecular Film for Self‐Healing Actuator with Multiple‐Stimuli Responses
Authors: Zhang Ke‐Qi , ur Rehman Khalil , Gao Jian
Published: June 2023

The structural vulnerability and immobility of the multi‐responsive actuators restrict its application in soft robots. Hence, self‐healing film actuators based on interfacial supramolecular crosslinking and hierarchical structural design have been developed. The graphene oxide supramolecular film with asymmetric structure reveals excellent reversible deformation under different trigger signals like moisture, thermal, and infrared light. Meanwhile, it shows a good healing property based on supramolecular interaction, achieving the structure restoration and reconstitution of stimuli‐responsive actuators (SRA). The re‐edited SRA realizes reverse reversible deformation under the same external stimuli. To enhance the functionality of graphene oxide‐based SRA, the reconfigurable liquid metal could be modified on the surface of the graphene oxide supramolecular film at low temperature (defined as LM‐GO) due to its compatibility for hydroxyl. The fabricated LM‐GO film displays satisfactory healing property and good conductivity. Besides, the self‐healing film maintains strong mechanical strength, which can bear more than 20 grams of weight. This study provides a novel strategy to fabricate self‐healing actuator with multiple responses, accomplishing the functional integration of the SRAs.
Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis
Authors: Perez‐Cornago Aurora , Smith‐Byrne Karl , Hazelwood Emma , Watling Cody Z. , Martin Susan , Frayling Timothy , Lewis Sarah , Martin Richard M. , Yaghootkar Hanieh , Travis Ruth C. , Key Timothy J.
Published: June 2023

Background

The associations of adiposity with aggressive prostate cancer risk are unclear. Using two‐sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer.

Methods

We examined the association of these genetically predicted adiposity‐related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases).

Results

In inverse‐variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61–1.19), 0.80 (0.53–1.23) and 0.97 (0.88–1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer.

Conclusions

We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.
Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and comparison of pathogenesis
Authors: Bai Natalie A. , Richardson Christie S.
Published: June 2023

Lyme disease is the most common vector‐borne illness in the United States and has been causing significant morbidity since its discovery in 1977. It is well‐documented that about 10% of patients properly treated with antibiotics never fully recover, but instead go on to develop a chronic illness dubbed, posttreatment Lyme disease syndrome (PTLDS) characterized by severe fatigue, cognitive slowing, chronic pain, and sleep difficulties. This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome (ME/CFS), a strikingly similar syndrome. In the majority of the PTLDS studies, at least four of the six major symptoms of ME/CFS were also noted, including substantial impairment in activity level and fatigue for more than 6 months, post‐exertional malaise, and unrefreshing sleep. In one of the included PTLDS articles, 26 of the 29 ME/CFS symptoms were noted. This study adds to the expanding literature on the post‐active phase of infection syndromes, which suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.
Mechanistic, Functional, and Clinical Aspects of Pro‐inflammatory Cytokine Mediated Regulation of ADME Gene Expression in 3D Human Liver Spheroids
Authors: Klöditz Katharina , Tewolde Eida , Nordling Åsa , Ingelman‐Sundberg Magnus
Published: June 2023

During systemic inflammation, pro‐inflammatory cytokines alter metabolism and transport of drugs affecting the clinical outcome. We used an in vivo like human 3D liver spheroid model to study the effects and mechanisms of pro‐inflammatory cytokines on the expression of 9 different genes encoding enzymes responsible for the metabolism of > 90% of clinically used drugs. Treatment of spheroids with pathophysiologically relevant concentrations of IL‐1β, IL‐6, or TNFα resulted in a pronounced decrease in mRNA expression of CYP3A4 and UGT2B10 within 5 hours. The reduction of CYP1A2, CYP2C9, CYP2C19, and CYP2D6 mRNA expression was less pronounced, whereas the pro‐inflammatory cytokines caused increased CYP2E1, and UGT1A3 mRNA expression. The cytokines did not influence expression of key nuclear proteins, nor the activities of specific kinases involved in the regulation of genes encoding drug metabolizing enzymes. However, ruxolitinib, a JAK1/2 inhibitor, inhibited the IL‐6 dependent increase in CYP2E1 and the decrease in CYP3A4 and UGT2B10 mRNA expression. We evaluated the effect of TNFα in hepatocytes in 2D plates and found a rapid decrease in drug‐metabolizing enzyme mRNA both in the absence or presence of the cytokines. Taken together, these data suggest that pro‐inflammatory cytokines regulate multiple gene‐ and cytokine‐specific events seen in in vivo and in 3D but not in 2D liver models. We propose that the 3D spheroid system is suitable for the prediction of drug metabolism under conditions of inflammation and constitutes a versatile system for short‐ and long‐term preclinical and mechanistic studies of cytokine‐induced changes in drug metabolism.
Hydrothermal Fabrication of Carbon‐Supported Oxide‐Derived Copper Heterostructures: A Robust Catalyst System for Enhanced Electro‐Reduction of CO2 to C2H4
Authors: Tandava Venkata S. R. K. , Spadaro Maria Chiara , Arbiol Jordi , Murcia‐López Sebastián , Morante Joan Ramón
Published: June 2023

Anthropogenic CO2 can be converted to alternative fuels and value‐added products by electrocatalytic routes. Copper‐based catalysts are found to be the star materials for obtaining longer‐chain carbon compounds beyond 2e− products. Herein, we report a facile hydrothermal fabrication of a highly robust electrocatalyst: in‐situ grown heterostructures of plate‐like CuO−Cu2O on carbon black. Simultaneous synthesis of copper‐carbon catalysts with varied amounts of copper was conducted to determine the optimum blend. It is observed that the optimum ratio and structure have aided in achieving the state of art faradaic efficiency for ethylene >45 % at −1.6 V vs. RHE at industrially relevant high current densities over 160 to 200 mA ⋅ cm−2. It is understood that the in‐situ modification of CuO to Cu2O during the electrolysis is the driving force for the highly selective conversion of CO2 to ethylene through the *CO intermediates at the onset potentials followed by C−C coupling. The excellent distribution of Cu‐based platelets on the carbon structure enables rapid electron transfer and enhanced catalytic efficiency. It is inferred that choosing the right composition of the catalyst by tuning the catalyst layer over the gas diffusion electrode can substantially affect the product selectivity and promote reaching the potential industrial scale.