bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Traditional Chinese Veterinary Medicine in the Treatment of Cognitive Dysfunction: A Systematic Review and Meta-Analysis
Authors: Nokay Catherine , Shiau Deng-Shan
Published: July 2023

The objective of this systematic review study was to assess the efficacy of traditional Chinese medicine (TCM) or traditional Chinese veterinary medicine (TCVM) in the treatment of cognitive dysfunction. The study considered the similarities in Alzheimer’s disease (AD) and canine cognitive dysfunction (CCD). The initial literature search resulted in 573 relevant clinical and nonclinical studies. Three categories of controlled clinical trials in AD patients were selected for review: placebo control (20), conventional medicine control (126), and integrated treatment (183). The studies were reviewed and those that met the inclusion criteria were selected for meta-analysis. The review found that 10 placebo-controlled studies, 38 conventional medicine-controlled studies, and 38 integrated studies were qualified for meta-analysis. In placebo-controlled studies, meta-analyses based on improvements in Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) found statistical significance in the MMSE (p=8.74×10-7), ADAS-cog (p=0.0085), and overall p-value (p=3.66×10-17), suggesting that the TCM treatments were significantly more effective than placebo. In conventional treatment-controlled studies, results from the meta-analyses also suggest that TCM treatments were significantly more effective than conventional treatments based on the overall p-value (p=1.67×10-23) and improvement in MMSE (p=0.0002). In the integrated treatment studies, the meta-analyses findings suggest that TCM-integrated treatments were significantly more effective than conventional treatments alone (overall p-value: p=1.82×10-48 and p=0.0050 in MMSE improvements). Based on this systematic review and considering the similarities in pathology in the human and canine, TCVM may be helpful to lessen suffering and improve the quality of life in patients with canine cognitive dysfunction.
QUALITY MANAGEMENT OF HEALTH SERVICES ON PATIENT SATISFACTION AT MONTELLA PRIVATE HOSPITAL WEST ACEH DISTRICT
Authors: Mulya Wulandari  , Susy Sriwahyuni  , Dahlan Gunawan
Published: July 2023

The world of health is one of the most important factors in life. Over time, it is only natural for the world of health to provide fast and appropriate services in order to create a comfortable, conducive and motivated work environment. Hospital health services are one type of public service that is often accessed by the public. At any time the community will always demand quality services, even though these demands are often not as expected, because services still display a convoluted, slow, expensive and tiring nature because the community is still positioned as the party serving not being served. The purpose of this study was to determine the effect of the quality of health services on patient satisfaction at the Montella Private Hospital, West Aceh District. The method used in this study is simple linear regression where this method is used to determine the linear relationship between the independent variable (X) and the dependent variable (Y). In addition, the simple linear regression method aims to determine the direction of the relationship between the independent variable and the dependent variable. whether positive or negative and to predict the value of the dependent variable if the value of the independent variable increases or decreases. The data used is data from the answers to the questionnaire using a Likert scale. Based on the results of the study, it can be concluded that testing from previous observational data indicates that the magnitude of the influence of Health Service Quality on Patient Satisfaction at Montella Private Hospital as measured through the questionnaire question indicators distributed to respondents in the Very high and good category because it is influenced by 97.50% ( R Square value) so that it is proven that the variable Quality of Health Services has a large positive and significant effect on patient satisfaction at Montella Private Hospital, while the remaining percentage value of 2.50% affects variables not examined in this study's observations.
POLSKA W RANKINGACH – POZYCJA KRAJU W ZESTAWIENIU PORÓWNAWCZYM NA TLE WYBRANYCH WSKAŹNIKÓW MIĘDZYNARODOWYCH
Authors:   Akademia Nauk Stosowanych Gospodarki Krajowej, Rogala-Lewicki Adam
Published: July 2023

The year 2022 is a good time to summarize Polish battles for a better life, a better country and respect from others1. Certainly, few people remember that in 1989 Poland was one of the poorest countries in Europe at that time. The state – bankrupt in the period of the political transformation – could boast a GDP per capita of approx. 6 000 $. Only Romania was in a worse position. Bulgaria at that time had a GDP per capita of $ 7,330. In Hungary, Slovakia, Lithuania, Latvia and Estonia well over 8,000 $. From the Czechs, with their GDP of 11,000 $, there was a civilization gap. Needless to say, Poland’s GDP was dramatic compared to the average of the European Communities, accounting for only 38% of the average GDP of the European Community. The average Pole lived at a level slightly exceeding 1⁄3 of the average European on the west of the Elbe. In relation to the Dutch or the Swedes, this disproportion was even greater. Compared to the citizen of Luxembourg, the average Pole was at the bottom of the poverty on the old continent.
EVALUASI KEBUTUHAN RUANG PARKIR SEPEDA MOTOR DI AREA GEDUNG FKIP DAN FST UNIVERSITAS QOMARUL HUDA BADARUDDIN BAGU
Authors: Januriad Januriad , Widhi Dharma S. Bagus , Utami Yuliarti
Published: July 2023

Parking is a problem that is often encountered in terms of transportation, especially in locations that have high activity, one of which is on campus. This study discusses the need for parking space in the FKIP UNIQHBA and FST Building Areas. The research method used for the preparation of this study was a quantitative method by anticipating work and then conducting field surveys at the parking locations of the FKIP and FST UNIQHBA Buildings based on the Directorate General of Land Transportation in 1998). The results of the research on parking characteristics obtained include: the maximum parking duration of a motorcycle is 525 minutes, the average duration of a motorcycle is 222.76 minutes. The accumulation of motorcycle parking is 221 vehicles. The maximum parking volume for motorbikes is 414 vehicles during the survey (07.00-17.00). motorcycle parking index of 202.75%. Motorcycle parking turnover is 2.04 times. The static capacity in the FKIP and FST UNIQHBA Building Area is 109 SRP. Maximum motorcycle occupancy is 202.75% (10.30-10.45 hours). Parking Space Requirement (KRP) that must be provided for motorcycle parking is 243 SRP. From the results of the overall calculation analysis, it can be concluded that the existing parking space capacity is not sufficient, there is still a shortage of 134 SRP for motorcycles
СОЦІАЛЬНИЙ КОНЦЕПТ РЕФОРМУВАННЯ САМОВРЯДУВАННЯ НА РІВНІ СІЛЬСЬКИХ ТЕРИТОРІАЛЬНИХ ГРОМАД
Authors: Пасічник Ю.В.
Published: July 2023

В непростих суспільних умовах теперішнього розвитку України актуалізується проблема стабільного функціонування сільських територіальних громад. У цьому контексті, незважаючи на здійснену територіальну децентралізацію, залишається низка прогалин у соціальному зрізі, які з врахуванням вибраного курсу на вступ до Європейського Союзу, необхідно заповнювати. Серед таких прогалин виокремлюються окремі напрями щодо необхідності реформування самоврядування для поліпшення інфраструктури, оперативного надання якісних соціальних послуг, транспортне сполучення. Саме тому наявні проблеми пропонується вирішувати на основі пропонованого соціального концепту.
Impella Implantation as a Bridge to Surgery for Repair of Aorto-Right Ventricular Fistula Following Prosthetic Valve Endocarditis: A Case Report
Authors: Narita Masahiko , Tsutsui Masahiro , Ushioda Ryohei , Kikuchi Yuta , Shirasaka Tomonori , Kamiya Hiroyuki
Published: July 2023

For patients with cardiogenic shock, delaying surgery with mechanical circulatory support is reported to yield better outcomes than emergency surgery. We report on an 82-year-old man diagnosed with vertebral osteomyelitis with concomitant infective endocarditis. Chest radiographs revealed a growing abscess, which resulted in an aorto-right ventricular fistula. Providing Impella support allowed for hemodynamic stabilization prior to surgery. The patient had an uneventful postoperative course and reported to be well in a follow-up 1 year later. Impella support can be used as a bridge to surgery for repairing fistulous tract formation in patients in cardiogenic shock.
Creation Music Pepanggulan Ki Gepang | Tabuh Kreasi Pepanggulan, “Ki Gepang”
Authors: Praditya Deny , Saptono Saptono , Partha I Ketut
Published: July 2023

Ki Gepang is a percussion composition created by pepanggulan using the gamelan Gong Kebyar as a medium of expression. As for the theme raised in this work, namely the sword, the sword that the stylist raised was not just any sword but an heirloom sword left by Manik Angkeran which was used to slash the tail of Naga Basuki in the story of the Selat Bali , which until now is still sacred by the people of Banjar Tegal, Bebalang , Bangli. The stylist's interest in taking up this theme is because the stylist is attracted by the magical and sacred aura of the heirloom and the stylist wants to transform the sharpness, majesty and sacredness of the heirloom into a percussion composition created by pepanggulan. In the musical structure, the stylist uses a tri angga structure, namely pengawit (Head), pengawak (Body), pengecet (Legs) as a basic reference in the stylist's work. And in the creative process, the stylist uses the traditional Balinese method, which in this concept says that there are 3 (three) stages for the process of creating a work of art, namely the conception stage (ngarencana), the execution stage (ngewangun) and ngebah/maedeng.
Bayu Wetan As An Inspiration For The Percussion Of The Hips Creations | Bayu Wetan Sebagai Inspirasi Tabuh Kreasi Pepanggulan
Authors: Putra Dwi Antara , Yulianti Ni Ketut Dewi
Published: July 2023

Garapan ini dituangkan ke dalam bentuk komposisi Tabuh Kreasi Pepanggulan. Beranalogi dengan ungkapan rasa si penata melalui fenomena alam hembusan angin timur. Ide ini muncul ketika penata sedang duduk di salah satu tempat duduk di rumah penata sendiri, dan penata merasakan hembusan angin yang datangnya dari arah timur yang berhembus dengan rapi dan membawa suasana keindahan, kesejukan dengan kekuatan angin tersebut penata  merasakan bagaimana suasana pada pagi hari. Berpijak dari fenomena tersebut penata mendapatkan inspirasi untuk merealisaikan keindahan, kesejukan, dan kekuatan angin timur yang telah menghampiri jiwa si penata ke dalam sebuah bentuk komposisi Tabuh Kreasi Pepanggulan yang dikemas dengan menggunakan struktur Tri Angga yaitu Kawitan, Pengawak, dan Pengecet. Bayu dan wetan merupakan dua kata yang memiliki arti yang berbeda, akan tetapi penata akan membuat arti tersebut ke dalam satu garapan utuh. Kata “bayu” dalam Bahasa Sansekerta berarti angin, dan kata “wetan”  berarti timur rupanya putih aksaranya “dang” dengan saktinya Sang Sadyoja (Bandem, 1986). Jadi “bayu wetan” dapat diartikan sebagai konsep filosopis dari Dewa Iswara yang menguasi arah timur dan sebagai pengendali arah mata angin di bagian timur.
Musical Composition “Segehan Wong” | Komposisi Karawitan “Segehan Wong”
Authors: Gung Wisnu I Gusti Ngurah Wisnu Dharma , Sudiana I Nyoman
Published: July 2023

Segehan Wong merupakan sebuah upakara atau sesajen yang dimana sesajen tersebut adalah sebuah simbul sebagai bentuk perlawanan umat Hindu di bali terhadap Virus Covid-19 ini di ekspresikan dalam bentuk karya musik inovatif yang di sajikan dengan gambelan bali. Di mana memiliki bagian perbagian di mana di dalam bagian pertama itu adalah kepala dari segehan yang berwarna putih yang memiliki arti agar pemikiran nagatif  dapat di atasi oleh kesucian di lanjutkan ke bagian kedua yang di mana itu di dalam segehan terdapat pada badan yang berwarna brumbun memiliki arti agar semua perasaan hadir dan terpancar dari hati yang paling dalam dan juga yang meliputi kedua tangan yang di mana tangan kiri berwarna kuning yang memiliki arti kemuliaan dan tangan kanan berwarna merah memiliki arti keberanian dan pada bagian ketiga meliputi kaki dari segehan yang di mana berwarna hitam  yang memiliki arti berani melangkah melewati kegelapan dunia yang sedang hadir.
RESEÑA. DIARIO, MARIE BASHKIRTSEFF
Authors: García-Sinausía Sandra
Published: July 2023

Reseña del libro de Marie Bashkirtseff, titulado Diario
Use of online material in teaching general practice
Authors: Jorgensen Merete , Witt Klaus , Mäkelä Matrjukka , Siersma Volkert , Winther Bang Christine
Published: July 2023

In the general practice course at Copenhagen University, students record videos of their consultations in general practice. At university, the videos are discussed with a teacher and peers. Simulated video consultations were produced to support learning. The aim of this study was to evaluate the effect of adding simulated consultation videos to standard teaching.

Final semester students (N=587) were assigned by the university to six groups and received more online teaching material one step at a time. A questionnaire and a test video consultation measured the change in students’ ability to identify patient-centered elements in a consultation pre-and post-course. Effect sizes were calculated as the difference between the pre-and post-course measures divided by the mean-variance before the course.

The overall teaching effect size (ES) was positive (0,67). A high average ES of 0.94 was found for the communication questions, which included most of the patient-centered elements. Introducing simulated video consultations did not increase awareness of patient-centered elements. However, an increase in clinical skills was demonstrated.

Showing simulated video consultations from general practice increase the students awareness of clinical cases in general practice and can be supplement to the clinical teaching.
Håbefuld pædagogik og online-undervisning på videregående uddannelser
Authors: Riis Marianne , Mikkelsen Stinus L.S. , Albrechtsen Thomas R.S.
Published: July 2023

Formålet med denne artikel er at bidrage teoretisk til videreudvikling af online-undervisning ved at præsentere og diskutere teorier om håb som mulige pædagogiske tilgange. Baggrunden herfor er hovedresultater fra en undersøgelse af online-undervisning på danske videregående uddannelser under corona-nedlukningen. Overordnet viste undersøgelsen, at der var udfordringer med at få denne form for undervisning til at fungere meningsfuldt. Anvendt som ekstrem case kan undersøgelsen sige noget om forskellige indlejrede udfordringer i online-undervisning, der blot blev tydeliggjort under nedlukningen. I artiklen fremhæves tre forskellige udfordringer, og der opstilles krav til hvordan uddannelsesteknologier fremadrettet kan og bør imødekomme en håbefuld pædagogik. Hovedpointen er, at håb kan udgøre et alternativ til en forenklet dikotomisk tilgang til feltet og dermed være med til at nuancere tilgangen til online-undervisning.
Hybrid teknologiforståelse
Authors: Andersen Lars Bo , Danholt Peter , Ratner Helene Friis
Published: July 2023

Denne artikel undersøger politiske og teoretiske muligheder for at udvikle en hybrid teknologiforståelsesfaglighed, hvilket vil sige en faglighed, der ikke baserer sig på et modsætningsforhold mellem mennesker og teknologier, subjekter og objekter eller kulturer og naturer, men derimod omfavner disse fænomener som sammenblandede og hybride. Artiklen indleder med at sammenfatte forskning i hybriditet fra Science and Technology studies (STS) med særlig fokus på Bruno Latours filosofi og begrebssæt i værket Vi har aldrig været moderne. Herefter analyseres forholdet mellem mennesker og teknologier i det retningsgivende politiske arbejde omkring teknologiforståelse for at identificere muligheder for hybrid teknologiforståelse. Og endelig diskuterer artiklen hvordan STS-begreberne om netværk, translation, matters of concern og performativitet kan informere en videreudvikling af de eksisterende kompetenceområder fra forsøgsfaget til i højere grad at omfavne teknologier, mennesker og samfund som hybride fænomener.
Læreruddannelsens vidensgrundlag efter reformen
Authors: Bjerre Jørn , Dorf Hans
Published: July 2023

Med udgangspunkt i Basil Bernsteins teori om viden, kompetence og performance,diskuterer artiklen det, den betegner som læreruddannelses vidensgrundlag. Detkonkrete udgangspunkt er bekendtgørelsen for uddannelseselementet Almenundervisningskompetence (fra 2013-reformen), som sammenlignes med det tilsvarendefag i den tidligere læreruddannelse, Almen didaktik. Via denne sammenligningargumenteres der for, at læreruddannelsens vidensgrundlag ikke har bevægetsig i retning af det øgede fokus på kompetence, som ligger i uddannelsens aktuelleselvbeskrivelse – men derimod har bevæget sig i retning af et øget fokus på performance.Videre argumenteres der for, at det fokus på generiske kompetencer, somtilstræbes via bevægelsen mod kompetencer, ikke vil kræve mindre, men et størrefokus på domænespecifi k viden.
Biomechanical comparisons between straight and bend sprinting in athletic sprint events
Authors:   , Bagley Ashley John
Published: July 2023

During bend sprinting, the continuous need to change direction affects athletes' whole-body mechanics. Continuously changing direction results in athletes not being able to achieve the same velocities on the bend as seen during straight-line sprinting. The aim of this thesis was to identify technique and performance differences between bend and straight-line sprinting. Two studies were conducted, one empirical study with experienced bend sprinters and one scoping review synthesising the existing bend sprinting literature. No differences were found in performance, push time, or most kinetic variables when analysing the effect of the bend during block starts compared with straight-line sprinting. However, there were reductions in vertical force on the bend compared with straight-line sprinting, which may negatively impact initial steps after block exit by reducing step length. Therefore, the bend reduces performance in subsequent race phases after block exit, potentially because athletes line their blocks up straight to increase anterior velocity. The results from the scoping review found that the effectiveness of strength training, which targets the performance descriptors, lower body kinematics, and ground reaction forces, should be further explored. A focus should be how athletes can better maintain variables closer to those during straight-line sprinting. Determining which variables are closely related to performance in sprinters who have greater velocities on the bend, and sprinters who can better maintain their velocity on the bend compared with straight-line sprinting, would help improve all bend sprinters. Additionally, statistical analysis such as statistical parametric mapping would provide additional information on the characteristics of the waveform that differentiate performers that may be lost when analysing discrete variables. Finally, advancements in technology should be explored by biomechanists to capture data ecologically during training and competition. Overall, changes in performance on the bend occur post block exit. However, a decrease in vertical force may impact the first few steps by reducing step length and, therefore, velocity. Variables related to better bend sprinters need to be identified using statistical analysis such as parametric mapping and advances in technology. An intervention study could then evaluate the effectiveness of strength training targeting the performance descriptors, lower body kinematics, and ground reaction forces, providing insights into improving bend sprinting performance.
Optimisation of the antimicrobial peptide Smp24 and its derivatives
Authors:   , Bertelsen Magnus Gammelgaard
Published: July 2023

The global increase in antimicrobial resistance development has created a critical need for the development of novel antimicrobial agents. Antimicrobial peptides (AMPs) are one such class of novel antimicrobials, but they have several disadvantages such as high manufacturing cost and low selectivity that must be addressed before they can achieve clinical use. In this study the relatively large size and high cytotoxic activity of the natural, venom derived AMP Smp24 were addressed using several different approaches. A formulation approach was investigated by incorporation of the peptide into sol-gel coatings in order to inhibit or prevent the growth of bacterial biofilms, showing that the unique physiochemical properties of the peptide can be utilized to improve and control the properties of the coating. Furthermore, a drug design approach was also used, based on several stages. Firstly, an investigation of the peptide structure was done creating a regional breakdown of the 3D structure and mechanism of action of the early stages of the pore formation using planar patch clamp electrophysiology. A bridge was built between the structure and mechanism via the use of molecular dynamics simulations of the peptide-bilayer interactions in order to establish a structure mechanism relationship. Based on this relationship several truncated variants of the parent peptide were designed an evaluated, first in silico showing that the simulations can give direct feedback during the design process and in vitro showing that two of the truncated analogs had both smaller size, improved antimicrobial properties and reduced cytotoxic properties compared to the parent peptide. The best analogs were further developed via amino acids substitutions in two iterations, with a total of 19 analogs evaluated in silico with 11 of those also being evaluated in vitro. Again, multiple analogs were produced with improved antimicrobial activity and selectivity. Overall, additional insight into the structure and biophysical behaviour of Smp24 was gained and utilized to guide the design of new analogs with significantly smaller size and improved selectivity without loss of antimicrobial activity relative to the parent peptide.
Exploring Capitalism in the Economy of Early Modern Gujarat: The Structure and Organization of Textile Production and the Market in Surat in the Eighteenth Century
Authors: Nadri Ghulam A.
Published: July 2023

Objective/Context: This study has two main goals. First, it explores the structural and organizational dynamics of the textile industry and the market in early modern India, eighteenth-century Gujarat in particular. In this context, the paper also examines how the ascendancy of the English East India Company in the political economy of Western India and the region’s transition to a colonial economy impacted the industry, the market, and the relationship between weavers and merchants. Methodology: This paper draws on the literature on textile production and trade, as well as on capitalism in early modern and colonial India, and uses evidence about Gujarat from the records of the English and Dutch East India Companies. Originality: This paper argues that the relationship between weavers and merchants in Surat/Gujarat was dynamic, complementary, and at times, contentious. None of them was able to dominate the relationship, and the English East India Company could not substitute a coercion-based production relation for a market-based one. Conclusions: The dynamics—such as product specialization and innovation, division of labor, the contract system, and forward buying—point to the existence of commercial capitalism in the textile economy. The paper also argues that because of the extraordinary diversity of people engaged in the industry and their varying professional and transactional experiences, it is relevant to recognize that commercial capitalism represents a mode of production that co-existed with others in the economy.
“Soft Gold” Before the Gold Rush: Sea Otter Pelts in the “Competitive Expansion” of Merchant Capitalism and the Creation of a Pacific Ocean Economy
Authors: Giráldez Arturo , Richard Analiese
Published: July 2023

Objective/Context: In this article, we examine how Chinese demand for pelts—of sea otters and other marine mammals—fueled the eighteenth-century competitive expansion of European and later American merchants and explorers in the Pacific islands and along the Pacific coast of North America. Sea otter pelts were a commodity directly linked to the creation of a Pacific Ocean economy, and California’s colonization resulted from imperial dynamics to which this trade gave rise. Methodology: Using both primary and secondary sources, we examine how these merchants’ quest to supply the lucrative Chinese luxury market with furs—“soft gold”—brought them into contact with indigenous peoples whose livelihoods and commercial networks would also be recruited into this global market but on quite unequal terms and with devastating consequences. Originality: The growth of this Pacific trade throughout the eighteenth century fueled geopolitical rivalries that led to the colonization of California with a system of missions and military garrisons (presidios) and, eventually, to a new ecology as a result of plants and animals brought from New Spain before the Gold Rush and the Treaty of Guadalupe Hidalgo. Many, including Marx and Engels, have claimed that the Gold Rush contributed significantly to the dynamics of industrial capitalism; nevertheless, we argue that its conditions of possibility were laid out centuries earlier via the complex geopolitical and ecological connections through which this Pacific economy was articulated. Conclusions: During the eighteenth century, the Pacific’s products were extracted and commodified in circuits whose demand center was China. It is precisely the prior existence of these global markets—centered on silver and “soft gold,” or sea otter furs—that explains the presence of Europeans and Americans in California eager to prospect for the yellow metal in 1848.
Las caravanas de camellos como modo de producción en la Afro-Eurasia posclásica. Una entrevista con Richard W. Bulliet
Authors: Bulliet Richard , Castro Constanza , Yazdani Kaveh
Published: July 2023

Objective/Context: This interview discusses the expansion of the camel caravan trade between roughly the sixth and sixteenth centuries. Wheeled transportation—used in West Asia during the Roman and Sasanid periods—basically disappeared around 500 CE, when camel caravans took over the transport business. Since the domestication of camels in Southern Arabia, sometime between 4000 and 3000 bce, and its adaptation over centuries to carrying loads in the sparsely vegetated desert, the network of camel caravan activity gradually extended way beyond its original center. The caravan system increasingly expanded into many areas of West and Central Asia, North Africa, North India, North-West China, and, to some extent, even parts of “Islamicate” Europe (Andalusia and Sicily). Indeed, camel caravans became the most extensive network of overland transportation the world had seen before the rise of railroad transportation. Originality: In this interview, Richard W. Bulliet discusses how camel caravans replaced wheeled transport in the “Middle East” and how the caravan system restructured many facets of socio-economic and political life in the Arid Zone between approximately 500 and 1500 ce. Conclusion: The depth of this restructuring, he argues, can be compared to changes in the mode of production commonly observed by economic historians elsewhere, including those associated with the rise of mercantile capitalism.
Mitochondrial MICOS complex genes, implicated in hypoplastic left heart syndrome, maintain cardiac contractility and actomyosin integrity
Authors: Birker Katja , Ge Shuchao , Kirkland Natalie J , Theis Jeanne L , Marchant James , Fogarty Zachary C , Missinato Maria A , Kalvakuri Sreehari , Grossfeld Paul , Engler Adam J , Ocorr Karen , Nelson Timothy J , Colas Alexandre R , Olson Timothy M , Vogler Georg , Bodmer Rolf
Published: July 2023

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We performed whole genome sequencing (WGS) on 183 HLHS patient-parent trios to identify candidate genes, which were functionally tested in the Drosophila heart model. Bioinformatic analysis of WGS data from an index family of a HLHS proband born to consanguineous parents prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of them, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. These defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complex’s role in maintaining cristae morphology and ETC assembly. Five additional HLHS probands harbored rare, predicted damaging variants in CHCHD3 or CHCHD6. Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes from these patients for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 (goliath, E3 ubiquitin ligase), or SPTBN1 (β-Spectrin, scaffolding protein) caused synergistic heart defects, suggesting the likely involvement of diverse pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.
Presenting a sham treatment as personalised increases the placebo effect in a randomised controlled trial
Authors: Sandra Dasha A , Olson Jay A , Langer Ellen J , Roy Mathieu
Published: July 2023

Background:

Tailoring interventions to patient subgroups can improve intervention outcomes for various conditions. However, it is unclear how much of this improvement is due to the pharmacological personalisation versus the non-specific effects of the contextual factors involved in the tailoring process, such as the therapeutic interaction. Here, we tested whether presenting a (placebo) analgesia machine as personalised would improve its effectiveness.

Methods:

We recruited 102 adults in two samples (N1=17, N2=85) to receive painful heat stimulations on their forearm. During half of the stimulations, a machine purportedly delivered an electric current to reduce their pain. The participants were either told that the machine was personalised to their genetics and physiology, or that it was effective in reducing pain generally.

Results:

Participants told that the machine was personalised reported more relief in pain intensity than the control group in both the feasibility study (standardised β=−0.50 [–1.08, 0.08]) and the pre-registered double-blind confirmatory study (β=−0.20 [–0.36, –0.04]). We found similar effects on pain unpleasantness, and several personality traits moderated the results.

Conclusions:

We present some of the first evidence that framing a sham treatment as personalised increases its effectiveness. Our findings could potentially improve the methodology of precision medicine research and inform practice.

Funding:

This study was funded by the Social Science and Humanities Research Council (93188) and Genome Québec (95747).
Reconstructing the transport cycle in the sugar porter superfamily using coevolution-powered machine learning
Authors: Mitrovic Darko , McComas Sarah E , Alleva Claudia , Bonaccorsi Marta , Drew David , Delemotte Lucie
Published: July 2023

Sugar porters (SPs) represent the largest group of secondary-active transporters. Some members, such as the glucose transporters (GLUTs), are well known for their role in maintaining blood glucose homeostasis in mammals, with their expression upregulated in many types of cancers. Because only a few sugar porter structures have been determined, mechanistic models have been constructed by piecing together structural states of distantly related proteins. Current GLUT transport models are predominantly descriptive and oversimplified. Here, we have combined coevolution analysis and comparative modeling, to predict structures of the entire sugar porter superfamily in each state of the transport cycle. We have analyzed the state-specific contacts inferred from coevolving residue pairs and shown how this information can be used to rapidly generate free-energy landscapes consistent with experimental estimates, as illustrated here for the mammalian fructose transporter GLUT5. By comparing many different sugar porter models and scrutinizing their sequence, we have been able to define the molecular determinants of the transport cycle, which are conserved throughout the sugar porter superfamily. We have also been able to highlight differences leading to the emergence of proton-coupling, validating, and extending the previously proposed latch mechanism. Our computational approach is transferable to any transporter, and to other protein families in general.
Effort cost of harvest affects decisions and movement vigor of marmosets during foraging
Authors: Hage Paul , Jang In Kyu , Looi Vivian , Fakharian Mohammad Amin , Orozco Simon P , Pi Jay S , Sedaghat-Nejad Ehsan , Shadmehr Reza
Published: July 2023

Our decisions are guided by how we perceive the value of an option, but this evaluation also affects how we move to acquire that option. Why should economic variables such as reward and effort alter the vigor of our movements? In theory, both the option that we choose and the vigor with which we move contribute to a measure of fitness in which the objective is to maximize rewards minus efforts, divided by time. To explore this idea, we engaged marmosets in a foraging task in which on each trial they decided whether to work by making saccades to visual targets, thus accumulating food, or to harvest by licking what they had earned. We varied the effort cost of harvest by moving the food tube with respect to the mouth. Theory predicted that the subjects should respond to the increased effort costs by choosing to work longer, stockpiling food before commencing harvest, but reduce their movement vigor to conserve energy. Indeed, in response to an increased effort cost of harvest, marmosets extended their work duration, but slowed their movements. These changes in decisions and movements coincided with changes in pupil size. As the effort cost of harvest declined, work duration decreased, the pupils dilated, and the vigor of licks and saccades increased. Thus, when acquisition of reward became effortful, the pupils constricted, the decisions exhibited delayed gratification, and the movements displayed reduced vigor.
Periaqueductal gray activates antipredatory neural responses in the amygdala of foraging rats
Authors: Kim Eun Joo , Kong Mi-Seon , Park Sanggeon , Cho Jeiwon , Kim Jeansok J.
Published: July 2023

Pavlovian fear conditioning studies propose that the interaction between the dorsal periaqueductal gray (dPAG) and basolateral amygdala (BLA) functions as a prediction error mechanism for fear memory formation. However, their roles in responding to naturalistic predatory threats, where predictive cues are ambiguous and do not afford reiterative trial-and-error learning, remain unexplored. We conducted single-unit recordings in rats engaged in an ‘approach food-avoid predator’ behavior, characterizing dPAG and BLA neurons responsive to a looming robot predator. Opto-stimulation of dPAG induced fleeing and increased BLA activity. Notably, BLA neurons activated by dPAG stimulation displayed an immediate response to the robot and heightened synchronous activity compared to non-responsive BLA neurons. Furthermore, anterograde and retrograde tracer injections into the dPAG and BLA, respectively, indicate that the paraventricular nucleus of the thalamus (PVT) may mediate dPAG-to-BLA neurotransmission. Our findings suggest that dPAG and BLA interactions, potentially via the PVT, underlie an innate antipredatory defensive mechanism.
FMRP regulates postnatal neuronal migration via MAP1B
Authors: Messaoudi Salima , Allam Ada , Stoufflet Julie , Paillard Theo , Le Ven Anaïs , Fouquet Coralie , Doulazmi Mohamed , Trembleau Alain , Caille Isabelle
Published: July 2023

The fragile X syndrome (FXS) represents the most prevalent form of inherited intellectual disability and is the first monogenic cause of autism spectrum disorder. FXS results from the absence of the RNA-binding protein FMRP (fragile X messenger ribonucleoprotein). Neuronal migration is an essential step of brain development allowing displacement of neurons from their germinal niches to their final integration site. The precise role of FMRP in neuronal migration remains largely unexplored. Using live imaging of postnatal rostral migratory stream (RMS) neurons in Fmr1-null mice, we observed that the absence of FMRP leads to delayed neuronal migration and altered trajectory, associated with defects of centrosomal movement. RNA-interference-induced knockdown of Fmr1 shows that these migratory defects are cell-autonomous. Notably, the primary Fmrp mRNA target implicated in these migratory defects is microtubule-associated protein 1B (MAP1B). Knocking down MAP1B expression effectively rescued most of the observed migratory defects. Finally, we elucidate the molecular mechanisms at play by demonstrating that the absence of FMRP induces defects in the cage of microtubules surrounding the nucleus of migrating neurons, which is rescued by MAP1B knockdown. Our findings reveal a novel neurodevelopmental role for FMRP in collaboration with MAP1B, jointly orchestrating neuronal migration by influencing the microtubular cytoskeleton.
Reward contingency gates selective cholinergic suppression of amygdala neurons
Authors: Kimchi Eyal Y. , Burgos-Robles Anthony , Matthews Gillian A. , Chakoma Tatenda , Patarino Makenzie , Weddington Javier , Siciliano Cody A. , Yang Wannan , Foutch Shaun , Simons Renee , Fong Ming-fai , Jing Miao , Li Yulong , Polley Daniel B. , Tye Kay M.
Published: July 2023

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward – even in prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs.
In vivo
electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex (PFC). Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic-receptor-signaling, while also facilitating firing in GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.
Reshaping the research landscape in Brazil
Authors: Crestana Gustavo Schiavone , Mendes Jéssica , Corrêa dos Santos Renato Augusto , Winck Flávia Vischi
Published: July 2023

Brazil would benefit from a long-term strategy for science and innovation that improves the standing of both science and scientists in the country.
Årsrapport 2022
Authors: Solberg Tore K. , Ingebrigtsen Tor , Olsen Lena Ringstad , Thyrhaug Anette Moltu
Published: July 2023

Nasjonalt kvalitetsregister for ryggkirurgi ble opprettet i 2007 og utvidet til å inkludere nakkekirurgi i 2012. Registeret har som mål å forbedre kvaliteten på kirurgisk behandling av degenerative rygg- og nakkelidelser. Registeret måler pasientrapporterte utfall (PROM) og erfaringer (PREM) med validerte skårer. Datakvaliteten er god med dokumentert aktualitet, korrekthet, reliabilitet, kompletthet og sammenlignbarhet. Årlig blir det publisert en rapport med oversikt over resultater for alle sykehus og kirurgiske enheter i Norge som utfører rygg og nakkekirurgi.
Development of a circHIPK3-based ceRNA network and identification of mRNA signature in breast cancer patients harboring BRCA mutation
Authors: Lian Qi-xin , Song Yang , Han Lili , Wang Zunxian , Song Yinhui
Published: July 2023

Background

Exploring the regulatory network of competing endogenous RNAs (ceRNAs) as hallmarks for breast cancer development has great significance and could provide therapeutic targets. An mRNA signature predictive of prognosis and therapy response in BRCA carriers was developed according to circular RNA homeodomain-interacting protein kinase 3 (circHIPK3)-based ceRNA network.

Method

We constructed a circHIPK3-based ceRNA network based on GSE173766 dataset and identified potential mRNAs that were associated with BRCA mutation patients within this ceRNA network. A total of 11 prognostic mRNAs and a risk model were identified and developed by univariate Cox regression analysis and the LASSO regression analysis as well as stepAIC method. Genomic landscape was treated by mutect2 and fisher. Immune characteristics was analyzed by ESTIMATE, MCP-counter. TIDE analysis was conducted to predict immunotherapy. The clinical treatment outcomes of BRCA mutation patients were assessed using a nomogram. The proliferation, migration and invasion in breast cancer cell lines were examined using CCK8 assay and transwell assay.

Result

We found 241 mRNAs within the circHIPK3-based ceRNA network. An 11 mRNA-based signature was identified for prognostic model construction. High risk patients exhibited dismal prognosis, low response to immunotherapy, less immune cell infiltration and tumor mutation burden (TMB). High-risk patients were sensitive to six anti-tumor drugs, while low-risk patient were sensitive to 47 drugs. The risk score was the most effective on evaluating patients’ survival. The robustness and good prediction performance were validated in The Cancer Genome Atlas (TCGA) dataset and immunotherapy datasets, respectively. In addition, circHIPK3 mRNA level was upregulated, and promoted cell viability, migration and invasion in breast cancer cell lines.

Conclusion

The current study could improve the understanding of mRNAs in relation to BRCA mutation and pave the way to develop mRNA-based therapeutic targets for breast cancer patients with BRCA mutation.
Chemical weathering rates and controlling mechanisms of glacial catchments within different climate regimes in the Tibetan Plateau
Authors: Guo Xiao , Zhao Zimiao , Liu Wenjing , Sun Huiguo , Xu Zhifang
Published: July 2023

Background

Continental weathering plays an important role in regulating atmospheric CO2 levels. Chemical weathering in glacial areas has become an intensely focused topic in the background of global change compared with other terrestrial weathering systems. However, research on the weathering of the glacial areas in the Yarlung Tsangpo River Basin (YTRB) is still limited.

Methods

In this article, the major ions of the Chaiqu and Niangqu catchments in the YTRB have been investigated to illustrate the chemical weathering rates and mechanisms of the glacier areas in the YTRB.

Results

Ca2+ and HCO${}_{3}^{-}$ dominate the major ions of the Chaiqu and Niangqu rivers, accounting for about 71.3% and 69.2% of the TZ+ of the Chaiqu (the total cations, TZ+ = Na+ + K+ + Ca2 + + Mg2+, in µeq/L), and about 64.2% and 62.6% of the TZ+ of the Niangqu. A Monte Carlo model with six end-members is applied to quantitatively partition the dissolved load sources of the catchments. The results show that the dissolved loads of the Chaiqu and Niangqu rivers are mainly derived from carbonate weathering (accounting for about 62.9% and 79.7% of the TZ+, respectively), followed by silicate weathering (about 25.8% and 7.9% of the TZ+, respectively). The contributions of precipitation and evaporite to the Chaiqu rivers are about 5.0% and 6.2%, and those to the Niangqu rivers are about 6.3% and 6.2%. The model also calculated the proportion of sulfuric acid weathering in the Chaiqu and Niangqu catchments, which account for about 21.1% and 32.3% of the TZ+, respectively. Based on the results calculated by the model, the carbonate and silicate weathering rates in the Chaiqu catchment are about 7.9 and 1.8 ton km−2 a−1, and in the Niangqu catchment, the rates are about 13.7 and 1.5 ton km−2 a−1. The associated CO2 consumption in the Chaiqu catchment is about 4.3 and 4.4 × 104 mol km−2 a−1, and about 4.3 and 1.3 × 104 mol km−2 a−1 in the Niangqu catchment. The chemical weathering rates of the glacier areas in the YTRB show an increasing trend from upstream to downstream. Studying the weathering rates of glacier catchments in the Tibetan Plateau (TP) reveals that the chemical weathering rates of the temperate glacier catchments are higher than those of the cold glacier catchments and that lithology and runoff are important factors in controlling the chemical weathering of glacier catchments in the TP. The chemical weathering mechanisms of glacier areas in the YTRB were explored through statistical methods, and we found that elevation-dependent climate is the primary control. Lithology and glacial landforms rank second and third, respectively. Our results suggest that, above a certain altitude, climate change caused by tectonic uplift may inhibit chemical weathering. There is a more complex interaction between tectonic uplift, climate, and chemical weathering.
Comparative Evaluation of Periapical Healing Outcome Following Non Surgical Endodontic Treatment in Single-visit versus Multiplevisit in Type 2 Diabetes Mellitus Patients: A Randomised Clinical Study
Authors: Savaliya Krushn , Kishan KV , Shah Nimisha , Mavani Harshit Tushar , Shroff Manan Gaurang , Darak Devashree
Published: July 2023

Introduction: Apical periodontitis is very common in those with diabetes mellitus. Diabetes alters immunity, which impacts how periapical tissue heals. The decision between one-visit and multiple-visit root canal therapy is currently up for debate. Aim: To compare periapical healing following single-visit endodontic therapy and multiple-visit endodontic therapy in type 2 diabetic patients by clinical assessment. Materials and Methods: The present randomised singleblinded clinical trial was conducted in the Department of Conservative Dentistry and Endodontics, KM Shah Dental College and Hospital, Vadodara, Gujarat, India, from December 2017 to October 2019. A total of 46 patients having type 2 diabetes, indicated for root canal treatment participated in the study and were randomly split into two groups: group I: Single-visit endodontic treatment and group II: Multiple-visit endodontic treatment. Thereafter, endodontic treatment was carried out on all the patients and the patients were recalled for evaluation at 1-week, 3-month and 6-month time intervals. The clinical assessment was done based on the absence of pain, swelling and sinus tract formation. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) software version 20.0. Results: Results showed that the success rate based on clinical assessment at one week for a single-visit and multi-visit group was 56.52% for both the groups and at three months 90.47% and 86.36%, respectively. At six months, the single-visit group reported 100% success, while the multi-visit group reported 95% success. However, the difference between the groups was not statistically significant. Conclusion: Within the limitation of the study, it was concluded that clinically, a higher success rate was found after six months in patients having type 2 diabetes mellitus who were treated in a single-visit, which was not statistically significant.