bluuebunny/crossref_metadata_2025 huggingface dataset:
TAFSIR ASAS MONOGAMI DALAM SURAH AN-NISÄ€â€™ AYAT 3 DAN 129
Authors: Dhuha Syamsud
Published: February 2023

Salah satu asas dalam perkawinan adalah monogami yang menyatakan bahwa seorang pria hanya diperbolehkan mempunyai seorang istri, begitupun sebaliknya. Terdapat poin dalam ayat al-Qurâ€™an yang menyatakan asas perkawinan adalah monogami yaitu pada surat an-Nisaâ€™ ayat 3 dan 129. Tujuan dari penelitian ini adalah untuk mengetahui tafsir dari ayat monogami dari berbagai kalangan mufassir, baik mufassir klasik maupun mufassir kontemporer dalam memaknai arti secara harfiah maupun ijmali, serta asbabun nuzul dan historitas monogami dalam Islam. Metode penelitian dalam artikel ini menggunakan penelitian kualitatif. Sumber hukum yang digunakan adalah bahan hukum primer berupa kitab-kitab tafsir dan bahan hukum sekunder berupa artikel atau jurnal yang berkaitan dengan tema yang dibahas. Dalam penelitian ini terlihat bahwa ulama klasik sangat menyetujui monogami, karena beranggapan bahwa setiap suami tidak akan berlaku adil dalam mengemban rumah tangga yang lebih dari seorang istri. Namun bagi ulama kontemporer menilai bahwa poligami diberikan rukhsah disertai sikap kehati-hatian karena ditakutkan tidak dapat berlaku adil. Monogami dalam Islam dipandang sebagai pernikahan yang idealis sedangkan poligami adalah pernikahan minimalis karena harus dengan prinsip kehati-hatian dalam berbuat keadilan dalam membangun keluarga harmonis.
PERANAN ISTRI DALAM RUMAH TANGGA PERSPEKTIF AL-QURâ€™AN DAN TINJAUANNYA DALAM FIKIH MUNAKAHAT
Authors: Fauziyah Ulil , Rozaq Abd
Published: February 2023

Pasangan suami-istri yang ideal adalah hubungan yang didasari dengan kebersamaan untu saling melengkapi kekurangan masing-masing. Hubungan yang tercipta dengan saling berbagai akan menciptakan keluarga yang sakinah mawaddah wa rahmah. Dalama proses hubungan berumah tangga tidak menutupkemungkinan terjadi masalah di antaranya persoalan peran istri dalam beruma tangga. Penelitian ingin mengkaji bagaimana perspektif al-Qurâ€™an tentang peran istri dalam rumah tangga dan tinjauannya dalam fikih munakahat. Metode penelitian ini menggunakan deskriptif kualitatif dengan menggunakan studi kepustakaan yang meliputi data primer separti al-Qurâ€™an dan pendapat para ulama, adapaun data sekundernya adalah berbagai kitab tafsir dan jurnal ilmiah. Hasil penelitiannya bahwa al-Qurâ€™an memberikan keleluasaan dalam pembagian peran antara suami-istri sesuai dengan kadar kemampuannya tanpa melampaui batas norma-norma agama dan kepatutan, sedangkan dalam tinjaun fikih munakahat ada sebagain ulama yang melarang istri untuk beraktifitas di luar, dan adapula yang membolehkan istri untuk berperan dalam ranah public di antaranya pendapat imam al-Suyuthi dan Yusuf al-Qaradhawi.
How opsonins drive bacterial uptake
Authors:   , Boero Elena Boero
Published: February 2023

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Current Percutaneous Management of Coronary Bifurcation Disease
Authors: Crimi Gabriele , Gianni Umberto
Published: February 2023

Coronary bifurcation disease (CBD) is frequently found in patients undergoing coronary interventions. Optimal management of CBD is technically demanding and therefore requires experience with different techniques, which should be tailored case-by-case. Provisional T-stenting is the recommended initial approach in most cases, however several two-stent techniques are described either as elective or as bailout strategy. This review describes the most common percutaneous techniques used to manage CBD, with advantages, drawbacks, and up-to-date medical evidence.
Desain Brand Kampung Wisata Kota Yogyakarta untuk Mendukung Daya Tarik Wisata Sepeda
Authors: Oentoro Kristian , Wiyatiningsih Wiyatiningsih , Amijaya Sita Yuliastuti
Published: February 2023

AbstrakKampung wisata di Kota Yogyakarta merupakan alternatif destinasi wisata yang menawarkan berbagai keunikan berbasis potensi lokal di 17 kampung wisata yang terdaftar pada Dinas Pariwisata Kota Yogyakarta. Wisata merupakan peluang pariwisata di era new normal yang dikembangkan oleh Pemerintah Kota Yogyakarta melalui pengembangan lima jalur sepeda wisata. Desain brand kampung wisata bertujuan untuk mendukung daya tarik wisata sepeda. Desain brand kampung wisata Kota Yogyakarta menggunakan metode desain Collaborative Destination Branding melalui proses studi awal, tahap perumusan arah branding, serta tahap perancangan desain branding. Hasil identifikasi menunjukan bahwa brand essence kampung wisata Kota Yogyakarta dirumuskan pada 3 kata kunci, yaitu: budaya, edukasi, dan keramahtamahan. Selain itu, identifikasi visual menunjukan warna ikonik kampung wisata adalah hijau, kuning, dan merah, sedangkan bentuk ikoniknya adalah Prajurit Kraton Yogyakarta (Bregada). Penerapan dari brand essence juga terdapat pada slogan dalam Bahasa Jawa, seperti ndherek langkung dan monggo pinarak yang mendukung keramahtamahan dalam kegiatan wisata sepeda di perkampungan. Perancangan brand kampung wisata Kota Yogyakarta telah diterapkan pada produk merchandise wisata sepeda seperti kaos pesepeda (jersey), tas serut, dan botol minum. Evaluasi bersama stakeholders menghasilkan penilaian dalam kategori baik sekali dan mampu merepresentasikan keunikan kampung wisata Kota Yogyakarta. Kata Kunci: Brand, Kampung Wisata, Wisata Sepeda, Yogyakarta AbstractTourism Villages in Yogyakarta City are alternative tourism attractions that offers uniqueness based on local potential from 17 tourism villages registered by the Yogyakarta City Tourism Office. Bicycle tourism is an opportunity since the new normal era developed by the Yogyakarta City Government through the development of five tourism bicycle tours. Tourism village brand design aims to support the promotion of bicycle tourism. Yogyakarta tourism village brand design uses the Collaborative Destination Branding design method through the initial study process, the formulation of branding directions, and the branding design stage. The identification results in the brand essence which is formulated in 3 keywords: culture, education, and hospitality. In addition, visual identification shows that the iconic colors are green, yellow, and red, and the iconic shape is the Soldiers of the Yogyakarta Kraton or Bregada. The brand essence applies slogans in Javanese, such as ndherek langkung and monggo pinarak which support hospitality in bicycle tourism activities. Design results are applied to bicycle merchandise products such as cycling jerseys, drawstring bags, and drinking bottles. The evaluation stage with stakeholders results in the assessment value with very good marks and represents the uniqueness of tourist villages and bicycle tours in Yogyakarta City. Keywords: Brand, Cycling Tourism, Tourism Village, Yogyakarta
The Analysis of Phonological Process on the English Consonant Sounds of Balinese EFL Students' Pronunciation
Authors: Utami Cahyani Putri , Putra Kresna Cahyadi
Published: February 2023

Abstract. This phonological analysis investigated the production of English consonant sounds produced by Balinese EFL students’ who speak an idiosyncratic native language as the main phenomena and examined the phonological rules represented descriptively and qualitatively. The data were gathered through digital recording and were observed by identifying the English pronunciation through note taking technique. This study was supported by the theories regarding phonological rules proposed by Odden (2013) and Hayes (2008). The Oxford Advanced Learner's Dictionary was used as a standard form of American pronunciation to compare the sounds produced by the students. The result of the study shows that the phonological errors represented in two ways of phonological rules: assimilation and deletion. First, assimilation occurred in the three positions of the word in three different sounds: [z], [ð] and [?]. Second, final deletion of specific phoneme /k/ and the deletion of aspirated allophones of the phoneme /p/. This study provides a significant contribution that there are several common phonological errors of English consonant sounds encountered by Balinese EFL students.Keywords: English consonants, phonological process, phonological rule, pronunciationAbstrak. Penelitian ini bertujuan untuk menganalisis produksi bunyi konsonan bahasa Inggris yang diproduksi oleh mahasiswa EFL Bali yang memiliki bahasa ibu yang idiosinkratik sebagai fenomena utama dan menentukan aturan fonologis secara deskriptif dan kualitatif. Data dikumpulkan melalui rekaman digital dan diamati dengan mengidentifikasi pengucapan melalui teknik pencatatan. Teori kaidah fonologis yang dikemukakan oleh Odden (2013) dan Hayes (2008) digunakan dalam penelitian ini. Selain itu, Oxford Advanced Learner's Dictionary digunakan dalam mengidentifikasi standar pengucapan bahasa Inggris untuk membandingkan dengan pengucapan siswa. Hasil penelitian menunjukkan bahwa pengucapan Bahasa Inggris oleh siswa dapat direpresentasikan dalam dua kaidah fonologis. Pertama, proses asimilasi terjadi pada tiga posisi kata dalam tiga bunyi berbeda: [z], [ð] dan [?]. Kedua, penghapusan fonem akhir tertentu yakni fonem /k/ dan penghapusan alofon fonem /p/. Penelitian ini memberikan kontribusi yang signifikan bahwa terdapat beberapa kesalahan fonologis yang umum terjadi pada bunyi konsonan bahasa Inggris yang ditemui oleh mahasiswa EFL Bali.Kata kunci: bunyi konsonan bahasa Inggris, kaidah fonologis, pelafalan, proses fonologis
Науково-технічний супровід індустріального будівництва зі збільшеним кроком несучих стін у сейсмічних районах
Authors: Nemchynov Iu.I. , Murashko O.V. , Yelkin O.V. , Ivanova O.M. , Kalinichenko A.S. , Barabash M.S. , Kubiyovych M.I. , Dikol K.V.
Published: February 2023

Робота присвячена вирішенню низки проблем, що виникають при експериментальному індустріальному будівництві конструктивних систем зі збільшеним кроком несучих стін на прикладі проекту, що реалізується компанією КП «Будова». Аналіз світового та вітчизняного досвіду проектування та будівництва великопанельних будівель в сейсмічних районах, натурних випробувань наслідків руйнівних землетрусів свідчить про значні переваги застосування таких конструктивних систем. Це обумовлено перш за все, значною жорсткістю та суттєво підвищеною якістю конструкцій, що виготовляються в заводських умовах. По-друге, індустріальне будівництво дозволяє скоротити терміни будівництва та трудомісткість при виготовлені та монтажі, що веде за собою зниження вартості будівництва. По третє, ступінь пошкодження великопанельних будівель під час землетрусу, як правило, на 1-2 ступені нижче, ніж інших конструктивних систем. При усіх перерахованих перевагах слід відмітити, що про застосування перекриттів прольотом більш ніж 6,4 м не проводилося. А на сьогоднішній день на планувальні рішення зі збільшеними прольотами є суттєвий попит на ринку житлової та громадської нерухомості. Тому напрям досліджень сейсмостійкості індустріальних будівель систем зі збільшеним кроком несучих стін є актуальним. До першочерговиих проблем, що виникають при розрахунку, при конструюванні, слід віднести особливості формування розрахункових моделей, розрахунку та аналізу результатів. Для вирішення проблем, що виникають при генерації розрахункових моделей та процесу розрахунку було модифіковано препроцесор та розрахунковий інструментарій програмного комплексу «ЛІРА-САПР», що спростило формування моделей та розрахунок з урахуванням особливостей роботи з урахуванням нелінійності. Для вирішення конструктивних проблем, що пов’язані з відхиленням від конструктивних вимог ДБН В.1.1-12 були розроблені компенсаційні заходи, для перевірки яких було проведено низку експериментальних лабораторних та натурних досліджень, які підтвердили можливість застосовувати запропоновану систему в районах з рівнем сейсмічних впливів 6-8 балів.
Numerical investigations of protective shells of NPP evergy units with pressurized water reactor (VVER)
Authors: Bambura A.M. , Sazonova I.R.
Published: February 2023

Most of the energy units of nuclear power plants in Ukraine are at the stage of exhausting their design lifespan. Therefore, the issue of extending the lifespan of energy units of nuclear power plants (NPP) and, consequently, assessing the residual life of protective shells is very acute. State Enterprise "The State Research Institute of Building Constructions" developed universal computer models of NPP energy units from VVER-1000 type V-302 and V-338, taking into account all the design features of protective shells, load connections and the possibility of varying the level of pre-tensioning of ropes. The developed models made it possible to evaluate the operability of a localizing safety system - a hermetic enclosure system in all operating modes, including a combination of loads during a design basis accident and a maximum design earthquake. The purpose of this work is: on the basis of numerous studies of the load-bearing capacity of the protective shells of energy units in all operating modes, to develop a methodology for determining the rational tension of the ropes in rows, at which the forces in the ropes of all three rows under the action of emergency load coupling during normal operation plus design basis accident plus the maximum design earthquake (NO + DBA + MDE) is distributed most evenly and, as a result, the probability of breaking the ropes of the outer row during an accident is reduced.
As a result of numerous studies of the load-bearing capacity of the protective shells of energy units in all modes of operation and the determination of the rational tension of the ropes in rows under the action of NO+DBA+MDE, the following has been established: minimum allowable tensile force of reinforcing ropes in the cylindrical part of the protective shell of the energy unit in the absence of two ropes; minimum allowable tensile force of reinforcing ropes in the cylindrical part of the protective shell of the energy unit in the absence of three ropes. The rational distribution of rope tension between the rows is determined, in which the efforts in the reinforcing ropes of all three rows under the action of NO+DBA+MDE are distributed most evenly and, as a result, the probability of breaking the ropes of the outer row in case of an accident is reduced.
Моделювання сейсмічного навантаження на систему «надземна споруда-грунт»
Authors: Horodetskyi A.S. , Barabash M.S. , Pysarevskyi B.Yu. , Henserskyi Yu.V.
Published: February 2023

У статті розглядаються проблеми моделювання динамічних впливів «надземна споруда – ґрунтова основа» на прикладі будівлі, що розташована в м. Одеса. Розглянуто особливості моделювання необмеженого напівпростору ґрунту. У програмному комплексі ЛІРА - САПР запропоновано чисельну процедуру формування рівнянь руху та, як окремий випадок, рівнянь рівноваги, у задачах, де є необмежені області. Цю процедуру впроваджено у вигляді нових скінченних елементів, що дало можливість формувати гібридні моделі MCE/SBFEM і розв’язувати практично будь-які фізично лінійні та нелінійні динамічні задачі у часі методом підсистем. Описано принципи нових скінченних елементів, розроблених у програмному комплексі ЛІРА-САПР. Ці скінченні елементи імітують взаємодію між обмеженою областю ґрунту та іншою частиною напівпростору. В основі даного елемента лежить метод масштабування границі скінченного елементу. Для перевірки елементів вирішуються дві задачі. Перша задача розглядає обмежений ґрунт, куди вводяться розроблені граничні скінченні елементи. Друга задача розглядає ґрунт порівняно великих розмірів. Граничні умови не впливають на поширення хвилі (умовно може розглядатися як необмежений напівпростір) через розміри ґрунту. Результати чисельного експерименту свідчать про те, що застосування розроблених скінченних елементів дає можливість створювати моделі, які відтворюють реальні умови роботи конструкцій будівлі за динамічних впливів.
Виконано аналіз методів розрахунку на динамічні навантаження, що застосовуються у сучасному будівництві на прикладі реального об'єкта, розташованого у Комінтернівському районі Одеської області. При моделюванні сейсмічного впливу застосовуються реальні акселерограми, записані під час землетрусу на будівельному майданчику об'єкта, що розглядається. Представлено методику, що дозволяє моделювати поведінку конструктивної системи будівлі або споруди на основі розроблених та реалізованих у програмному комплексі ЛІРА-САПР скінченних елементів, що моделюють згасання коливань.
ЗБЕРЕЖЕННЯ ЗАБУДОВИ КИЇВСЬКОГО МОДЕРНІЗМУ МИНУЛОГО СТОЛІТТЯ. ТЕХНІЧНИЙ СТАН БУДІВЛІ «ЗАЛІЗНИЧНИЙ РИНОК»
Authors: Крівєльов Леонід , Кафієв Константин
Published: February 2023

Будівельна галузь України 60-70 років мину-лого століття характеризується реалізацієюнових наукових і технічних рішень ефективнихзбірних залізобетонних конструкцій, методів про-ектування на засаді застосування електронноїобчислюваної техніки, нарешті, створеннямбудівель нової архітектури, у якій головним фор-моутворюючим засобом є просторові геометричніпобудови. Цей напрямок у забудові Києва отри-мав назву Київський модернізм та представленийпонад 70 об’єктами. Серед них дві будівлі критихринків, побудовані за експериментальними про-ектами архітектора Алли Анищенко.Об’єкт дослідження − циклічна будівля«Залізничний ринок» з покриттям у виглядівисячої залізобетонної оболонки і зовнішньоюґратчастою конічною стіною на вул. Кудряшова, 1,у Солом’янському районі Києва.Мета статті – оприлюднення результатів визна-чення технічного стану тримальних конструкційбудівлі після довготривалої експлуатації та виве-дення з експлуатаційного режиму. Наразі місцевоювладою вирішується питання щодо подальшо-го її використання. Вважається за необхіднезбереження об’єкта дослідження як взірця іпам’ятки архітектури, будівельної науки і техніки60-70 років минулого століття.Методи дослідження – вивчення та аналіз про-ектних та літературних матеріалів, опрацюван-ня відомостей з історії будівництва та експлуатаціїоб’єкта дослідження, візуальне обстеженнябудівельних конструкцій, визначення механічниххарактеристик бетону фундаментів, стін і покрит-тя неруйнівними методами.Дослідження встановили, що механічні тафізичні зміни тримальних конструкцій будівліпісля майже 50-ти років експлуатації не набуливідчутних негативних розмірів. Міцність бетонузалізобетонних конструкцій становить 90-100% відпроектної і може бути врахована у дослідженняхпри визначені категорії технічного стану кон-структивних складових будівлі.За умов проведення додатковихінструментальних досліджень пальового фун-дамента, включаючи дослідження основ безпо-середньо в зоні фундаментів, та перевірочнихрозрахунків відповідно до змін в будівельнихнормах і стандартах така інформація в подаль-шому має бути врахована в проектних рішенняхнового комплексу забудови. При цьому будівлякритого ринку має становити одну з головнихкомпозиційних частин.Результати дослідження передбачається впро-вадити у проект реконструкції об’єкту. Прогнозніприпущення щодо розвитку об’єктів досліджень– реконструкція аналогічних циклічних спорудрізного призначення: ринків, будівель спортив-них закладів, бюветів мінеральних вод тощо.
Artificial intelligence-augmented analysis of contemporary procedural, mortality, and cost trends in carcinoid heart disease in a large national cohort with a focus on the “forgotten pulmonic valve”
Authors: Monlezun Dominique J. , Badalamenti Andrew , Javaid Awad , Marmagkiolis Kostas , Honan Kevin , Kim Jin Wan , Patel Rishi , Akhanti Bindu , Halperin Dan , Dasari Arvind , Koutroumpakis Efstratios , Kim Peter , Lopez-Mattei Juan , Yusuf Syed Wamique , Cilingiroglu Mehmet , Mamas Mamas A. , Gregoric Igor , Yao James , Hassan Saamir , Iliescu Cezar
Published: February 2023

Background

Carcinoid heart disease is increasingly recognized and challenging to manage due to limited outcomes data. This is the largest known cohort study of valvular pathology, treatment (including pulmonary and tricuspid valve replacements [PVR and TVR]), dispairties, mortality, and cost in patients with malignant carcinoid tumor (MCT).

Methods

Machine learning-augmented propensity score-adjusted multivariable regression was conducted for clincal outcomes in the 2016–2018 U.S. National Inpatient Sample (NIS). Regression models were weighted by the complex survey design and adjusted for known confounders and the likelihood of undergoing valvular procedures.

Results

Among 101,521,656 hospitalizations, 55,910 (0.06%) had MCT. Patients with MCT vs. those without had significantly higher inpatient mortality (2.93 vs. 2.04%, p = 0.002), longer mean length of stay (12.20 vs. 4.62, p < 0.001), and increased mean total cost of stay ($70,252.18 vs. 51,092.01, p < 0.001). There was a step-wise increased rate of TVR and PVR with each subsequent year, with significantly more TV (0.16% vs. 0.01, p < 0.001) and PV (0.03 vs. 0.00, p = 0.040) diagnosed with vs. without MCT for 2016, with comparable trends in 2017 and 2018. There were no significant procedural disparities among patients with MCT for sex, race, income, urban density, or geographic region, except in 2017, when the highest prevalence of PV procedures were performed in the Western North at 50.00% (p = 0.034). In machine learning and propensity score augmented multivariable regression, MCT did not significantly increase the likelihood of TVR or PVR. In sub-group analysis restricted to MCT, neither TVR nor PVR significantly increased mortality, though it did increase cost (respectively, $141,082.30, p = 0.015; $355,356.40, p = 0.012).

Conclusion

This analysis reflects a favorable trend in recognizing the need for TVR and PVR in patients with MCT, with associated increased cost but not mortality. Our study also suggests that pulmonic valve pathology is increasingly recognized in MCT as reflected by the upward trend in PVRs. Further research and updated societal guidelines may need to focus on the “forgotten pulmonic valve” to improve outcomes and disparities in this understudied patient population.
Slope stability prediction based on adaptive CE factor quantum behaved particle swarm optimization-least-square support vector machine
Authors: Yang Jingsheng
Published: February 2023

Since the prediction of slope stability is affected by the combination of geological and engineering factors with uncertainties such as randomness, vagueness and variability, the traditional qualitative and quantitative analysis cannot match the recent requirements to judge them accurately. In this study, we expect that the adaptive CE factor quantum behaved particle swarm optimization (ACE-QPSO) and least-square support vector machine (LSSVM) can improve the prediction accuracy of slope stability. To ensure the global search capability of the algorithm, we introduced three classical benchmark functions to test the performance of ACE-QPSO, quantum behaved particle swarm optimization (QPSO), and the adaptive dynamic inertia weight particle swarm optimization (IPSO). The results show that the ACE-QPSO algorithm has a better global search capability. In order to evaluate the stability of the slope, we followed the actual project and research literature and selected the unit weight, slope angle, height, internal cohesion, internal friction angle and pore water pressure as the main indicators. To determine whether the algorithm is scientifically and practically feasible for slope deformation prediction, the ACE-QPSO-, QPSO-, IPSO-LSSVM and single least-square support vector machine algorithms were trained and tested based on a real case of slope project with six index factors as the input layer of the LSSVM model and the safety factor as the output layer of the model. The results show that the ACE-QPSO-LSSVM algorithm has a better model fit (R2=0.8030), minor prediction error (mean absolute error=0.0825, mean square error=0.0110) and faster convergence (second iteration), which support that the ACE-QPSO-LSSVM algorithm emthod is more feasible and efficient in predicting slope stability.
Abnormal vibration perception threshold alters the gait features in type 2 diabetes mellitus patients
Authors: Dong Lining , Hu Yanyun , Xu Lei , Zeng Hui , Shen Wenqi , Esser Patrick , Dawes Helen , Liu Fang
Published: February 2023

Objective

It is generally believed that gait characteristics of diabetic neuropathic patients differ from those of non-diabetic ones. However, it is still unclear how the abnormal foot sensation influences the gait during walking in type 2 diabetes mellitus (T2DM). For the purpose of gaining a better insight into the alterations of detailed gait parameters and figuring out important aspects in the gait indexes by peripheral neuropathy in elder T2DM patients, we compared the gait features in participants with normal glucose tolerance (NGT) controls and diabetic individuals complicated by peripheral neuropathy or not.

Subjects and methods

Gait parameters were observed during the 10-m walk on flat land among different conditions of diabetes in 1,741 participants from three clinical centers. Subjects were divided into four groups: persons with NGT were taken as the control group; patients with T2DM included three subgroups: DM control (no chronic complications), DM-DPN (DM complicated by only peripheral neuropathy), and DM-DPN+LEAD (DM complicated by both neuropathy and artery disease). The clinical characteristics and gait parameters were assessed and compared among these four groups. Analyses of variance were employed to verify possible differences of gait parameters between groups and conditions. Stepwise multivariate regression analysis was performed to reveal possible predictors of gait deficits. Receiver operating characteristic (ROC) curve analysis was employed to find any discriminatory power of diabetic peripheral neuropathy (DPN) for the step time.

Results

In participants burdened with DPN, whether complicated by lower extremity arterial disease (LEAD) or not, step time increased sharply (p < 0.05). Stepwise multivariate regression models showed that independent variables of gait abnormality were sex, age, leg length, vibration perception threshold (VPT), and ankle-brachial index (ABI) (p < 0.01). Meanwhile, VPT was a significant independent predictor of step time, spatiotemporal variability (SDA), and temporal variability (SDB) (p < 0.05). ROC curve analysis was explored to find the discriminatory power of DPN for the occurrence of increased step time. The area under the curve (AUC) value was 0.608 (95% CI: 0.562–0.654, p < 0.01), and the cutoff point was 538.41 ms accompanied by a higher VPT. A significant positive association was observed between increased step time and the highest VPT group [odds ratio (OR) = 1.83, 95% CI: 1.32–2.55, p< 0.01]. In female patients, this OR value elevated to 2.16 (95% CI: 1.25–3.73, p< 0.01).

Conclusions

In addition to sex, age, and leg length, VPT was a distinct factor that associated with altered gait parameters. DPN is associated with increased step time, and the step time increases with worsening VPT in type 2 diabetes.
Ectomesenchymal Six1 controls mandibular skeleton formation
Authors: Luo Songyuan , Liu Zhixu , Bian Qian , Wang Xudong
Published: February 2023

Craniofacial development requires intricate cooperation between multiple transcription factors and signaling pathways. Six1 is a critical transcription factor regulating craniofacial development. However, the exact function of Six1 during craniofacial development remains elusive. In this study, we investigated the role of Six1 in mandible development using a Six1 knockout mouse model (Six1−/−) and a cranial neural crest-specific, Six1 conditional knockout mouse model (Six1f/f; Wnt1-Cre). The Six1−/− mice exhibited multiple craniofacial deformities, including severe microsomia, high-arched palate, and uvula deformity. Notably, the Six1f/f; Wnt1-Cre mice recapitulate the microsomia phenotype of Six1−/− mice, thus demonstrating that the expression of Six1 in ectomesenchyme is critical for mandible development. We further showed that the knockout of Six1 led to abnormal expression of osteogenic genes within the mandible. Moreover, the knockdown of Six1 in C3H10 T1/2 cells reduced their osteogenic capacity in vitro. Using RNA-seq, we showed that both the loss of Six1 in the E18.5 mandible and Six1 knockdown in C3H10 T1/2 led to the dysregulation of genes involved in embryonic skeletal development. In particular, we showed that Six1 binds to the promoter of Bmp4, Fat4, Fgf18, and Fgfr2, and promotes their transcription. Collectively, our results suggest that Six1 plays a critical role in regulating mandibular skeleton formation during mouse embryogenesis.
Prognostic RNA-editing signature predicts immune functions and therapy responses in gliomas
Authors: He Yi , Zhang Xingshu , Zhang Sen , Zhang Yi , Xie Bo , Huang Meng , Zhang Junjie , Shen Lili , Long Wenyong , Liu Qing
Published: February 2023

Background: RNA-editing refers to post-transcriptional transcript alterations that lead to the formation of protein isoforms and the progression of various tumors. However, little is known about its roles in gliomas.

Aim: The aim of this study is to identify prognosis-related RNA-editing sites (PREs) in glioma, and to explore their specific effects on glioma and potential mechanisms of action.

Methods: Glioma genomic and clinical data were obtained from TCGA database and SYNAPSE platform. The PREs was identified with regression analyses and the corresponding prognostic model was evaluated with survival analysis and receiver operating characteristic curve. Functional enrichment of differentially expressed genes between risk groups was performed to explore action mechanisms. The CIBERSORT, ssGSEA, gene set variation analysis, and ESTIMATE algorithms were employed to assess the association between PREs risk score and variations of tumor microenvironment, immune cell infiltration, immune checkpoints, and immune responses. The maftools and pRRophetic packages were used to evaluate tumor mutation burden and predict drug sensitivity.

Results: A total of thirty-five RNA-editing sites were identified as prognosis-related in glioma. Functional enrichment implied variation of immune-related pathways between groups. Notably, glioma samples with higher PREs risk score exhibited higher immune score, lower tumor purity, increased infiltration of macrophage and regulatory T cells, suppressed NK cell activation, elevated immune function score, upregulated immune checkpoint gene expression, and higher tumor mutation burden, all of which implied worse response to immune therapy. Finally, high-risk glioma samples are more sensitive to Z-LLNle-CHO and temozolomide, while the low-risk ones respond better to Lisitinib.

Conclusion: We identified a PREs signature of thirty-five RNA editing sites and calculated their corresponding risk coefficients. Higher total signature risk score indicates worse prognosis and worse immune response and lower sensitivity to immune therapy. The novel PREs signature could help risk stratification, immunotherapy response prediction, individualized treatment strategy-making for glioma patients, and development of novel therapeutic approaches.
Identification of novel inhibitors against hantaviruses through 2D fingerprinting and molecular modeling approaches
Authors: Alshammari Abdulrahman
Published: February 2023

With the immensely growing outbreaks of hantavirus with still no effective treatment available, there is an urgent need of exploring new computational approaches which will target potential virulent proteins that will eventually reduce its growth. In this study, an envelope glycoprotein, Gn, was targeted. The glycoproteins, which are the sole targets of neutralizing antibodies, drive virus entry via receptor-mediated endocytosis and endosomal membrane fusion. Inhibitors are herein proposed to negate its action mechanism. On the basis of the scaffolds of favipiravir, a FDA compound already used against hantavirus, a library was designed using a 2D fingerprinting approach. Upon molecular docking analysis, the top four docked compounds—(1) favipiravir (-4.5 kcal/mol), (2) N-hydroxy-3-oxo-3, 4-dihydropyrazine-2-carboxamide (-4.7 kcal/mol), (3) N, 5, 6-trimethyl-2-oxo-1H-pyrazine-3-carboxamide (-4.5 kcal/mol), and (4) 3-propyl-1H-pyrazin-2-one (-3.8)—were prioritized on the basis of the lowest binding energies score. Through molecular docking, the best-categorized compound was subjected to molecular dynamics simulation for a 100-ns time span. Molecular dynamics sheds light on each ligand behavior within the active site. Among the four complexes, only favipiravir and 6320122 compound were found to be stable inside the pocket. This is due to the presence of common rings, pyrazine and carboxamide ring, which make a significant interaction with active key residues Furthermore, the MMPB/GBSA binding free energy analysis calculated for all complexes supported the dynamics results by calculating the most stable values for favipiravir complex (-9.9933 and -8.6951 kcal/mol) and for 6320122 compound complex (-13.8675 and -9.3439 kcal/mol), which demonstrated that the selected compounds have a proper binding affinity with the targeted proteins. The hydrogen bond analysis similarly revealed a strong bonding interaction. The results yielded a strong interaction between the enzyme and the inhibitor throughout the simulation; thus, the inhibitor has the potential to become a lead compound and could be subjected to experimental evaluation to unveil their blockage ability.
Transcriptome, Proteome, Histology, and Biochemistry Analysis of Oriental River Prawn Macrobrachium nipponense under Long-term Salinity Exposure
Authors: Fan Yaoran , Wu Xiao , Ling Feiyue , Wang Zefei , Ma Keyi , Xie Nan , Li Juanying , Feng Jianbin , Li Jiale
Published: February 2023

Salinity is an ecological factor affecting the physiology, survival, and distribution of crustaceans. Additionally, salinity fluctuation detrimentally affects the composition and biological process of crustaceans. As a significant commercial aquaculture species in China, Japan, and Southeast Asian countries, the oriental river prawn, Macrobrachium nipponense, can tolerate a wide range of salinity. The transcriptome, proteome, histology, and physiology analysis were utilized to explore the physiological responses and molecular mechanisms of salinity tolerance in M. nipponense. Through the three-month culture, the statistic of growth trait illustrated the relatively excellent performance of M. nipponense in low salinity, and the higher salinity exposure significantly affected the growth of M. nipponense. In terms of the histological analysis, the gills and hepatopancreas of M. nipponense suffered varying degrees of damage. Besides, the activities of the digestive, immune-related, and metabolic enzymes were calculated. These results indicated that salinity significantly influenced trypsin and amylase in hepatopancreas, especially in 14 ppt. The immune-related enzymes were activated in high salinity. Notably, the activity of metabolic enzymes was significantly low in 7 and 14 ppt, which testified that the 7 ppt to 14 ppt were near the isotonic point of M. nipponense. In gills, hepatopancreas, and muscle, high-throughput mRNA sequencing revealed 11356, 2227, and 1819 differentially expressed genes (DEGs) by comparing the 7, 14, and 21 ppt groups with the 0ppt group, respectively. The TMT-labeling proteome identified 439 and 230 differentially expressed proteins (DEPs) in gills and hepatopancreas through the comparison of the 7, 14, and 21 ppt groups to the 0 ppt group, respectively. Additionally, through the integration of transcriptome and proteome, several pathways related to salinity adaptation were enriched, including protein export, cGMP-PKG signaling pathway, Amino sugar and nucleotide sugar metabolism, and Glycine, serine and threonine metabolism. Besides, 16 up and down-regulated proteins and related DEGs were detected through KEGG enrichment analysis, including ETHE1, BIP, chitinase (E3.2.1.14), and SARDH. Notably, no significantly regulated proteins and related DEGs were recorded by the correlation of transcriptome and proteome of 0 ppt and 7 ppt in hepatopancreas. Thus, the optimum survival salinity of M. nipponense may range from 0 ppt to 7 ppt. Overall, these results may provide valuable insights into the mechanisms underlying the culture of M. nipponense in different salinity.
Intermittent Hypoxia Rewires the Liver Transcriptome and Fires up Fatty Acids Usage for Mitochondrial Respiration
Authors: Gaucher Jonathan , Vial Guillaume , Montellier Emilie , Guellerin Maëlle , Bouyon Sophie , Lemarie Emeline , Pelloux Véronique , Bertrand Anne , Pernet-Gallay Karin , Lamarche Frederic , Borel Anne-Laure , Arnaud Claire , Belaidi Elise , Clément Karine , Godin Ribuot Diane , Aron-Wisnewsky Judith , Pépin Jean-Louis
Published: February 2023

Sleep Apnea Syndrome (SAS) is one of the most common chronic diseases, affecting nearly one billion people worldwide. The repetitive occurrence of abnormal respiratory events generates cyclical desaturation-reoxygenation sequences known as intermittent hypoxia (IH). Among SAS metabolic sequelae, it has been established by experimental and clinical studies that SAS is an independent risk factor for the development and progression of non-alcoholic fatty liver disease (NAFLD). The principal goal of this study was to decrypt the molecular mechanisms at the onset of IH-mediated liver injury. To address this question, we used a unique mouse model of SAS exposed to IH, employed unbiased high-throughput transcriptomics and computed network analysis. This led us to examine hepatic mitochondrial ultrastructure and function using electron microscopy, high-resolution respirometry and flux analysis in isolated mitochondria. Transcriptomics and network analysis revealed that IH reprograms Nuclear Respiratory Factor- (NRF-) dependent gene expression and showed that mitochondria play a central role. We thus demonstrated that IH boosts the oxidative capacity from fatty acids of liver mitochondria. Lastly, the unbalance between oxidative stress and antioxidant defense is tied to an increase in hepatic ROS production and DNA damage during IH. We provide a comprehensive analysis of liver metabolism during IH and reveal the key role of the mitochondria at the origin of development of liver disease. These findings contribute to the understanding of the mechanisms underlying NAFLD development and progression during SAS and provide a rationale for novel therapeutic targets and biomarker discovery.
Exploration of teaching practice of analgesia and sedation in mainland China: CASER experience
Authors: Su Longxiang , Li Shu , Lou Ran , Liu Ying , Zhang Hua , Jiang Li
Published: February 2023

Objective

Analgesia and sedation assessments vary widely in clinical performance. This study investigated the cognition of intensivist and the importance of training for analgesia and sedation through the Chinese Analgesia and Sedation Education & Research (CASER) group training program.

Methods

A total of 107 participants studied the training courses on the “Sedation, Analgesia and Consciousness Assessment of Critically Ill Patients” held by CASER from June 2020 to June 2021. Ninety-eight valid questionnaires were recovered. The content of the questionnaire included the preface, general information of the trainees, students’ awareness of the importance of analgesia and sedation evaluation and related guidelines, and professional test questions.

Results

All respondents were senior professionals engaged in the ICU. A total of 92.86% believed that analgesia and sedation treatment were very important parts of the ICU, and 76.5% believed that they had mastered relevant professional knowledge. However, when evaluating the relevant professional theory and practice of the respondents from an objective point of view, it can be seen that only 28.57% of the respondents could reach the passing line in the specific case analysis scenario. Before participating in the training, 42.86% of the medical staff believed that analgesia and sedation treatment should be evaluated in the daily work of the ICU; after participating in the training, 62.24% of the medical staff believed that the evaluation was necessary and believed that they had improved after the training. Moreover, 69.4% of the respondents affirmed the necessity and significance of jointly undertaking the task of analgesia and sedation in Chinese ICUs.

Conclusion

This study revealed that the assessment of analgesia and sedation is not standardized in the ICU in mainland China. The importance and significance of standardized training for analgesia and sedation are presented. The CASER working group thus established has a long way to go in its future work.
Safety profile, antiviral capacity, and liver protection of a nasal therapeutic vaccine in patients with chronic hepatitis B: Five-year-follow-up outcomes after the end of treatment
Authors: Al Mahtab Mamun , Akbar Sheikh Mohammad Fazle , Aguilar Julio Cesar , Yoshida Osamu , Khan Sakirul , Gerardo Guillen Nieto , Hiasa Yoichi
Published: February 2023

Introduction

There is a pressing need to develop novel drugs for treating patients with chronic hepatitis B (CHB), as commercially available antiviral drugs are endowed with safety and efficacy concerns.

Methods

A phase III clinical trial was conducted with a therapeutic vaccine containing two antigens of the hepatitis B virus (HBV; named NASVAC) in 78 patients with CHB expressing both HBV DNA and elevated levels of alanine aminotransferase (ALT) in the blood. Five years after the end of treatment (EOT), 60 NASVAC-recipient patients were enrolled in this long-term follow-up study to evaluate the safety, antiviral potential, and liver-protective capacity of NASVAC.

Results

NASVAC exhibited an excellent safety profile 5 years after EOT. The levels of HBV DNA in the sera were reduced in 55 of the 60 patients, and 45 of them were negative for HBV DNA in the sera. ALT levels were also normalized in 40 of the 60 patients 5 years after EOT. None of the patients receiving NASVAC developed liver cirrhosis or cancer.

Discussion

The present study is the first to exhibit long-term follow-up data of a finite immune therapy for CHB that is safe and endowed with potent antiviral and liver-protecting capacities.
Low-dose topiramate and hydrochlorothiazide-associated early acute myopia and angle narrowing: A case report
Authors: Wu Chao , Pan Hong , Feng Shijun , Wang Xiaokun , Liu Zhaoqiang , Zhao Bojun
Published: February 2023

Purpose

To report a unique case of topiramate and hydrochlorothiazide associated with acute myopia and angle narrowing.

Patients and methods

A 34-year-old Asian woman presented with prominent binocular visual acuity decrease 6 h after taking only one dose of 25 mg topiramate, 25 mg hydrochlorothiazide, and 22.4 mg fluoxetine to lose weight. She was subsequently diagnosed with acute bilateral myopia and angle narrowing and was started on topical therapy.

Results

Initial examination revealed a decreased visual acuity of 20/100 bilaterally, an elevated intraocular pressure of 23 mmHg in the right eye and 24 mmHg in the left eye, suprachoroidal effusions, and angle narrowing. After the discontinuation of these drugs and the use of IOP-lowering medication, the patient made full recovery.

Conclusion

We speculate that there is a drug–drug interaction between topiramate and hydrochlorothiazide that may lead to the angle narrowing in a short time and at a low dose. Timely discontinuation of the drug usually leads to complete recovery within days to weeks.
A bibliometric analysis of 16,826 triple-negative breast cancer publications using multiple machine learning algorithms: Progress in the past 17 years
Authors: Wang Kangtao , Zheng Chanjuan , Xue Lian , Deng Dexin , Zeng Liang , Li Ming , Deng Xiyun
Published: February 2023

Background

Triple-negative breast cancer (TNBC) is proposed at the beginning of this century, which is still the most challenging breast cancer subtype due to its aggressive behavior, including early relapse, metastatic spread, and poor survival. This study uses machine learning methods to explore the current research status and deficiencies from a macro perspective on TNBC publications.

Methods

PubMed publications under “triple-negative breast cancer” were searched and downloaded between January 2005 and 2022. R and Python extracted MeSH terms, geographic information, and other abstracts from metadata. The Latent Dirichlet Allocation (LDA) algorithm was applied to identify specific research topics. The Louvain algorithm established a topic network, identifying the topic’s relationship.

Results

A total of 16,826 publications were identified, with an average annual growth rate of 74.7%. Ninety-eight countries and regions in the world participated in TNBC research. Molecular pathogenesis and medication are most studied in TNBC research. The publications mainly focused on three aspects: Therapeutic target research, Prognostic research, and Mechanism research. The algorithm and citation suggested that TNBC research is based on technology that advances TNBC subtyping, new drug development, and clinical trials.

Conclusion

This study quantitatively analyzes the current status of TNBC research from a macro perspective and will aid in redirecting basic and clinical research toward a better outcome for TNBC. Therapeutic target research and Nanoparticle research are the present research focus. There may be a lack of research on TNBC from a patient perspective, health economics, and end-of-life care perspectives. The research direction of TNBC may require the intervention of new technologies.
Fur functions as an activator of T6SS-mediated bacterial dominance and virulence in Aeromonas hydrophila
Authors: Li Jihong , Wu Zhihao , Hou Yuting , Zhang Yong-An , Zhou Yang
Published: February 2023

Aeromonas hydrophila, a ubiquitous bacterium in aquatic habitats with broad host ranges, has earned the nickname of a ‘Jack-of-all-trades’. However, there is still a limited understanding of the mechanism of how this bacterium fit the competition with other species in dynamic surroundings. The type VI secretion system (T6SS) is macromolecular machinery found in Gram-negative bacteria’s cell envelope that is responsible for bacterial killing and/or pathogenicity toward different host cells. In this study, the depression of A. hydrophila T6SS under iron-limiting conditions was detected. The ferric uptake regulator (Fur) was then found to act as an activator of T6SS by directly binding to the Fur box region in vipA promoter in the T6SS gene cluster. The transcription of vipA was repressed in Δfur. Moreover, the inactivation of Fur resulted in considerable defects in the interbacterial competition activity and pathogenicity of A. hydrophila in vitro and in vivo. These findings provide the first direct evidence that Fur positively regulates the expression and functional activity of T6SS in Gram-negative bacteria and will help to understand the fascinating mechanism of competitive advantage for A. hydrophila in different ecological niches.