bluuebunny/crossref_metadata_2025 huggingface dataset:
The Biophysical Modelling of the Living Structure
Authors: Vincze Janos , Vincze-Tiszay Gabriella
Published: July 2023

Today, the main development is to explore the relationship between structure and function as deeply as possible. Exact observation, precise conceptualization, the search and exploration of quantitative relations, the efforts made for a quantitative interpretation of phenomena, the development of comprehensive and mathematically formulated theories, the constant interaction of theoretical and experimental research generally serve as models in all areas of scientific research, also in relation to biology. Exact observation, precise conceptualization, the search and exploration of quantitative relations, the efforts made for a quantitative interpretation of phenomena, the development of comprehensive and mathematically formulated theories, the constant interaction of theoretical and experimental research generally serve as models in all areas of scientific research, also in relation to biology. The connection between the three fundamental sciences, physics, psychology and biology, is usually illustrated by intersecting circles arranged in the simplest way in a triangular. In order for a system to become the subject of scientific study, it must be precisely separated from its environment in space and time. Neither can exist without the other. No matter how elusive psychic events are, the organic substrate for this is provided by our individual biological structure.
Cone-Beam Computed Tomography Evaluation Of The Root Morphology Of The Anterior Maxillary And Mandibular Human Teeth In A Moroccan Subpopulation or Number Of Roots And Tooth Length (Part 1)
Authors: DHAIMY Said , LAGMOU Wahiba , BAITE Mohamed
Published: July 2023

The COVID-19 pandemic had many new post-viral sequelae some of which are yet to be detected. In our case series, we are presenting five patients with different ages, medical backgrounds, and presentations, who were diagnosed with Post COVID-19 Graves’ disease at Royal Hospital from January to December of 2020. The main reason behind this case series is to highlight the variability of presentation and the duration between exposure to the virus and the presentation. In addition, due to the similarity in the presentation of some of the symptoms between COVID-19 infection and Graves' Disease, most of those patients were delayed in getting the proper diagnosis of COVID-19-induced Graves' disease. Hence, this case series can aid in alerting primary care doctors for early detection of such cases and regular follow-up, which can positively impact our national healthcare system.
Limited Ortaklıklardaki Veto Hakkı ve Veto İşleminin Hükümsüzlüğüne Dair İncelemeler
Authors: SULU Muhammed
Published: July 2023

Limited ortaklıkları şahıs şirketlerine yaklaştıran bir düzenleme olan veto hakkı, mevzuatımızda detaylı olarak düzenlenmemiştir. Şirket sözleşmesi ile belirli veya belirlenebilir ortakların şahsına bahşedilebilecek bu hakkın gelişimine mevcut sistemde içtihat ve doktrinin yön vermesi beklenmektedir. Bu hususta İsviçre Borçlar Kanunu’ndaki düzenleme yol gösterici mahiyettedir. Sözleşmesel yenilik doğuran ve yönetsel müktesep hak niteliğindeki veto hakkının genel hatları ortaya konduktan sonra bu hakkın anonim ortaklıklar bakımından uygunluğu da tartışılmalıdır. Bunlara ilaveten makalenin cevap aradığı en temel sorular; veto hakkının hukuka uygun olarak kullanılmasının şartları ile özellikle hakkın kötüye kullanılması ve sadakat borcuna aykırılık bağlamında veto işleminin geçersiz kılınıp kılınmayacağı, geçersiz kılınması halinde ise mevcut genel kurul kararına etkisinin ne olacağıdır.
Pengggunaan Metode Guided Note Taking dalam Peningkatan Pembelajaran PAI
Authors: Wijayanti Titin
Published: July 2023

The purpose this research in increasing Islamic ecucation zakat and whole number in the students class VI of SD Negeri Karangjambu by using Guided Note Taking. The type of this research is Classroom Action Research (CAR) during 3 cycles, each cycle includes of planning, implementation, observation, and reflection. As sample is students class VI of SD Negeri Karangjambu, it includes 22 students. Technique of collecting data is used observation, interview, test, and documentation. The result shows that using  Guided Note Taking could increase Islamic ecucation zakat and whole number.
Problematika dan Solusi Manajemen Pembelajaran PAI di Perguruan Tinggi Keagamaan Islam
Authors: Haq Mai Al Mawangir Fathiyatul
Published: July 2023

This paper is motivated by problems in the management of PAI learning at PTKIwhich find problems from various aspects of the curriculum, lecturers, and learningprocess to student input that do not meet the minimum standards. This then requires asolution so that the objectives of PAI learning at PTKI can be achieved. The researchmethod used in this study is a qualitative method with a library approach.The results in this study to become a solution for the problems faced by lecturers atPTKI are that lecturers must master plan fullness, provide intrinsic motivation, be ableto carry out internalized evaluations, openness to experience, be flexible in learning,loyal, and have autonomy in determining learning forms. All of this will be successful ifit is supported by a curriculum that is anticipatory and adaptive to changing times andmakes students want to apply what they have learned and increase the desire forindependent learning
Penanaman Nilai-Nilai Religius dalam Rutinan Hadroh Mashoka (Majelis Sholawat) Putri kecamatan Kuwarasan
Authors: Irodati Fibriyan , Alfi Khaerum
Published: July 2023

Religious value is the highest and absolute value, this value is sourced from human beliefs and beliefs. Religious values ​​reflect faith in God Almighty which is manifested in the behavior of carrying out religious teachings and beliefs that they adhere to. Religious values ​​are values ​​regarding the concept of religious or religious life in the form of bonds or relationships that govern humans and their God, while the inculcation of religious values ​​can be through example, namely by following the stories of the Prophet, the birth of the Prophet and the Prophet's Family. Sholawat is a poem of praise and praise for the Prophet Muhammad SAW. The importance of Hadroh Mashoka Putri's routine activities in the Kuwarasan sub-district is as a means of learning to develop religious values ​​as well as to preserve religious culture.

This research is a field research, with qualitative research methods. This research was conducted at the Gandusari prayer room, Kuwarasan, Kebumen district. Data collection techniques in this study used interview, observation, and documentation techniques. The interview was conducted by a member of the NU Muslimat in Kuwarasan. The stages of data analysis techniques are data reduction, data analysis, and conclusions.

The results showed that the inculcation of religious values ​​through the hadroh Mashoka Putri activities consisted of three stages, namely by conveying or imparting knowledge which was then received, digested and understood by the participants so that it was carried out and carried out in their daily lives. After being applied in daily life, what they know they practice is in accordance with what is their example and what they learn from their role models.

Keywords: Religious Values, Sholawat
PENGGUNAAN HARTA WAKAF UNTUK KEPENTINGAN PRIBADI (STUDI KASUS DI MASJID JAMI’ AL-KHIDMAH KECAMATAN GONDANGREJO KARANGANYAR)
Authors: Ruwaifi Ruwaifi , Husaini Akhmad
Published: July 2023

Di antara syari’at Allah yang telah ditetapkan adalah wakaf. Wakaf merupakan suatu bentuk derma dengan memberikan sebagian harta kekayaannya secara sukarela dilakukan dengan tujuan mengharapkan pahala dan rida Allah. Sedangkan tujuan dari wakaf itu sendiri adalah memberikan manfaat harta yang diwakafkan untuk kemaslahatan umat. Oleh karenanya wakaf harus dikelola dengan bijak dan dilaksanakan dengan sebaik-baiknya berdasarkan dengan ketentuan syari’at agama Islam. Jenis penelitian ini menggunakan metode penilitian lapangan yang meliputi masyarakat penduduk sekitar yang terdiri dari jama’ah dan pengurus masjid. Dalam penelitian ini terdapat dua sumber data, yaitu data primer dan sekunder. Masjid Jami’ Al Khidmah memiliki berbagai jenis inventaris, sebagian barang-barang tersebut jarang digunakan oleh masjid, hal tersebut dapat memicu kerusakan pada barang yang tidak terpelihara dengan baik. Maka dengan kondisi tersebut tidak jarang harta wakaf tersebut digunakan oleh masyarakat yang membutuhkan, namun penggunaan tersebut hanya bersifat sementara, ada juga yang membelinya. Adapun hasil dari penelitian ini menunjukkan bahwa praktik yang dilakukan pengurus dan masyarakat sekitar Masjid Jami’ Al-Khidmah tidak sesuai dengan undang-undang di Indonesia yang melarang praktik tersebut, namun apabila statusnya meminjam karena kebutuhan mendesak maka masih diperbolehkan. Pemanfa’atan harta wakaf yang sudah tidak terpakai di masjid tersebut dihukumi menggunakan metode maslahah murasalah karena adanya maslahat yang lebih besar apabila dimanfaatkan dengan baik, dan apabila dibiarkan rusak akan menimbulkan kemudaratan.Kata Kunci:Wakaf, Harta Wakaf Yang Tidak Terpakai, Maslahah Murasalah.
The Conditional Associations of Authoritarianism with Americans’ Responses to COVID-19: An Out-of-Sample Replication
Authors: Ollerenshaw Trent
Published: July 2023

Seeking to understand why right-wing Americans adopted a lax response to COVID-19 despite psychological theories of threat sensitivity and dispositional security needs that might have predicted the opposite, Ollerenshaw (2022) shows dispositional authoritarianism was conditionally associated with Americans’ responses to COVID-19. Ollerenshaw (2022) finds authoritarianism was directly associated with greater concern for COVID-19 and concomitant health behaviors and preferences toward public health restrictions; indirectly, however, authoritarianism was associated with right-wing identification and cue-taking for politically engaged Americans, which reduced these individuals’ concern over COVID-19 and their willingness to adopt health behaviors and support public health restrictions. In this note, I replicate Ollerenshaw (2022) using the Voter Study Group survey. I similarly find authoritarianism was conditionally related to concerns about COVID-19 and preferences toward public health restrictions, with similar or larger effects. This replication adds weight to Ollerenshaw’s (2022) claim that psychological traits and political context jointly influenced Americans’ COVID-19 responses.
Biomaterial Artistry: Investigating the aesthetic expressions of voluminous form-giving applied to knit-bacterial cellulose composite textiles derived from material development in the context of footwear
Authors: De Lara Carolina
Published: July 2023

Present times are ablaze with environmental change, with fashion being no stranger to controversy as it struggles not only with keeping up with market demand, but making material production more efficient. Living materials and biocomposites, due to being easy, relatively inexpensive and quick to produce offer a biodegradable alternative to traditional materials. This project speculates how bacterial cellulose combined with knitted structures can occupy a prominent place in fashion and design thinking by visually discussing the morphology and role of volume as conforming components intended to develop footwear prototypes. Making methods are reassessed to accommodate the properties of Pemotex and bacterial cellulose, offering visual cues to revamp established methods of assembling shoes. Throughout the concept narrative, object and shoe are challenged by reconsidering the use of the last, aiming to initiate a dialogue to speculate about what shoes could be, as well as what and how they could become.
Strategic Planning and Preparation of Projects for Accessing Structural Funds for 2021-2027. Lessons Learned or History Repeating?
Authors: VASILIU Cristina , COJOCARU Stefan
Published: July 2023

The papers makes an analysis, with a focus on the North-East Region of Romania, of the stage of the drafting of strategic documents at national level and their correlation with regional and county planning documents, at the end of 2022. The analysis is carried out both in terms of the regional and local strategic documents, correlated with the national ones, as well as in terms of the perception held by some of the most important regional actors. The questions that the article pursues in its research approach are: How do we evaluate the preparation of projects for the new programming period 2021-2027 from the point of view of strategic planning and correlation with the documents adopted at the national/regional/local level? and . How do local actors perceive the influence on the absorption of European funds the drafting and adoption of strategic documents at national and regional level after the start of the programming period? The conclusions of the research: after two programming periods, there are still difficulties in connecting the priorities of the strategies and the preparation of local projects for accessing European funds based on the national and regional strategic documents.
Sociological Research on the Impact of the Covid-19 Pandemic on Student Preparation and the Development of Film Discourse
Authors: SHCHERBAK Olena , TRUBA Hanna , FILIPPOVA Nina , ROMANETS Valentyna , BORDENIUK Serhii , SHCHOKIN Rostyslav
Published: July 2023

This article aims to assess the impact of the pandemic on the education and film industry, specifically focusing on the formation of film discussion. The study examines the peculiarities of the educational process and cinema development trends during the pandemic and quarantine restrictions. The research methodology involves information systematization based on survey results. The study reveals that the majority of respondents perceive the pandemic as having a negative impact on education development, highlighting various challenges associated with distance learning. Additionally, a significant portion of respondents express concerns about the adverse effects of the pandemic on the film industry. The research identifies key development issues in education and the film industry. It suggests that digital advancements offer new opportunities for education development, while considering the changing worldview of the population due to the impact of mass diseases. In terms of film industry development, the study emphasizes the importance of considering economic and resource costs, as well as the need for digitalization during the pandemic. The findings highlight the need for strategic measures to address the challenges faced by the education and film industry during the pandemic. The study underscores the importance of leveraging digital tools and platforms for education and film production. It calls for a comprehensive approach that takes into account the evolving needs and preferences of the population, as well as the economic and resource considerations in the film industry. The research provides insights for policymakers, educators, and filmmakers to navigate the current landscape and make informed decisions to promote sustainable development and growth in these sectors.
Implementasi Strategi Intergrated Marketing Communication oleh UMKM Bidang Oleh-oleh Kuliner di Malang pada Masa Pandemi Covid-19
Authors: Yola Amalia Nisrina
Published: July 2023

Pandemi COVID-19 telah memberikan dampak yang cukup besar terutama pada kegiatan Usaha Mikro, Kecil, dan Menengah (UMKM), terutama UMKM yang bergerak di bidang kuliner. Dampak tersebut dialami oleh salah satu UMKM di Malang, yaitu Mimi Apple Pie Malang, di mana Mimi Apple Pie Malang harus mengalami penurunan omzet yang dialami selama awal pandemi. Tujuan dari penelitian ini adalah untuk mendeskripsikan implementasi integrated marketing communication yang dilakukan oleh Mimi Apple Pie Malang untuk dapat bertahan di tengah pandemi COVID-19. Metode penelitian yang dilakukan adalah menggunakan pendekatan kualitatif, dengan teknik pengumpulan data berupa wawancara mendalam dan observasi. Penelitian menunjukkan bahwa Mimi Apple Pie Malang dapat bertahan di tengah pandemi dengan menerapkan 5 dari 12 elemen promotion mix, yaitu dengan memanfaatkan direct marketing, social media, public relations, packaging yang menarik, serta kekuatan word-of-mouth.
 
he COVID-19 pandemic has had a considerable impact, especially on the activities of Micro, Small and Medium Enterprises (MSMEs), especially MSMEs engaged in the culinary field. This impact was experienced by one of the MSMEs in Malang, namely Mimi Apple Pie Malang, where Mimi Apple Pie Malang had to experience the decline in turnover experienced during the beginning of the pandemic. The purpose of this study is to describe the implementation of integrated marketing communication carried out by Mimi Apple Pie Malang to be able to survive during the COVID-19 pandemic. The research method used is a qualitative approach, with data collection techniques in the form of in-depth interviews and observations. Research shows that Mimi Apple Pie Malang can survive during a pandemic by applying 5 of the 12 elements of the promotion mix, namely by utilizing direct marketing, social media, public relations, attractive packaging, and the power of word-of-mouth
Pola Pengelolaan Arsip Secara Digital dalam Mendukung Efektivitas Organisasi di Dinas Pendidikan dan Kebudayaan Kota Bontang
Authors: Juniati Juniati , Nurdiansyah Aulia
Published: July 2023

The problem studied is the need for a digital-based archive management system within the Bontang City Education and Culture Office using digital-based archive management. The focus of the study is how to implement digital-based records management in records management so that the implementation of organizational activities can run efficiently and effectively. The purpose of this research is to encourage related devices to immediately adopt and implement digital-based archiving in order to succeed in the vision and mission of the organization so that organizational effectiveness and efficiency can be realized. Data collection techniques used are interviews, observation, and documentation. The results of this study indicate that a digital-based management system has not been implemented due to several factors, namely: (1) Employees who master digital-based records management are still limited, and (2) Lack of support from stakeholders in the use of digital-based records management systems. With this research, it is hoped that all parties can play an active role so that this digital-based implementation system can run as expected.
 
Masalah yang dikaji adalah tentang perlunya sistem pengelolaan arsip berbasis digital di lingkungan Dinas Pendidikan dan Kebudayaan Kota Bontang dengan menggunakan pengelolaan arsip berbasis digital. Fokus kajian adalah pengelolaan arsip berbasis digital dalam pengelolaan arsip agar pelaksanaan kegiatan organisasi dapat berjalan secara efisien dan efektif. Tujuan dari penelitian ini mengambarkan pengelolaan arsip berbasis digital dengan mengadopsi dan mengimplementasikan penyelenggaraan kearsipan berbasis digital demi mensukseskan visi dan misi organisasi agar efektivitas dan efisiensi organisasi dapat terwujud. Teknik pengumpulan data yang digunakan adalah wawancara, observasi, dan dokumentasi. Hasil Penelitian ini menunjukkan bahwa sistem penyelenggaraan berbasis digital belum terlaksana dikarenakan beberapa faktor yakni antara lain: (1) Pegawai yang menguasai pengelolaan arsip berbasis digital masih terbatas, dan (2) Kurangnya dukungan dari stakeholder dalam penggunaan sistem pengelolaan arsip berbasis digital. Dengan adanya penelitian ini, diharapkan semua pihak dapat ikut berperan aktif agar sistem penyelenggaraan berbasis digital ini dapat berjalan sesuai dengan apa yang diharapkan.
Assessing benefits and risks of incorporating plastic waste in construction materials
Authors: Cirino Erica , Curtis Sandra , Wallis Janette , Thys Tierney , Brown James , Rolsky Charles , Erdle Lisa M.
Published: July 2023

Plastic pollution and climate change are serious and interconnected threats to public and planetary health, as well as major drivers of global social injustice. Prolific use of plastics in the construction industry is likely a key contributor, resulting in burgeoning efforts to promote the recycling or downcycling of used plastics. Businesses, materials scientists, institutions, and other interested stakeholders are currently exploring the incorporation of plastic waste into building materials and infrastructure at an accelerated rate. Examples include composite asphalt-plastic roads, plastic adhesives, plastic-concrete, plastic/crumb rubber turf, plastic lumber, plastic acoustic/thermal insulation, plastic-fiber rammed earth, and plastic soil reinforcement/stabilizers. While some believe this to be a reasonable end-of-life scenario for plastic waste, research shows such efforts may cause further problems. These uses of plastic waste represent an ongoing effort at “greenwashing,” which both delays and distracts from finding real solutions to the plastic pollution crisis. Hypothesized effects of incorporating plastic waste in construction materials, including economic, environmental, human health, performance, and social impacts, are evaluated in this mini review. We compare known impacts of these treatments for plastic waste and provide recommendations for future research. Evidence shows that such practices exacerbate the negative ecological, health, and social impacts of plastic waste and increase demand for continued production of new (virgin) plastics by creating new markets for plastic wastes. We urge caution—and more research—before widely adopting these practices.
A chromEM-staining protocol optimized for cardiac tissue
Authors: Musolino Elettra , Pagiatakis Christina , Pierin Federica , Sabatino Daniele , Finzi Giovanna , Gornati Rosalba , Bernardini Giovanni , Papait Roberto
Published: July 2023

Three-dimensional (3D) chromatin organization has a key role in defining the transcription program of cells during development. Its alteration is the cause of gene expression changes responsible for several diseases. Thus, we need new tools to study this aspect of gene expression regulation. To this end, ChromEM was recently developed: this is an electron-microscopy staining technique that selectively marks nuclear DNA without altering its structure and, thus, allows better visualization of 3D chromatin conformation. However, despite increasingly frequent application of this staining technique on cells, it has not yet been applied to visualize chromatin ultrastructure in tissues. Here, we provide a protocol to carry out ChromEM on myocardial tissue harvested from the left ventricles of C57BL/6J mice and use this in combination with transmission electron microscopy (TEM) to measure some morphological parameters of peripheral heterochromatin in cardiomyocytes. This protocol could also be used, in combination with electron tomography, to study 3D chromatin organization in cardiomyocytes in different aspects of heart pathobiology (e.g., heart development, cardiac aging, and heart failure) as well as help to set-up ChromEM in other tissues.
Climbers for Bat Conservation: creating a citizen science program in Red River Gorge Kentucky
Authors: Gross Emily E. , Siebka Morgan E. , Schorr Robert A. , Solomon Jennifer N. , Davis Shawn K.
Published: July 2023

In recent years, North American bat populations have been presented with new conservation threats including white-nose syndrome. As these threats continue to impact bats it is important to locate and study these populations. Though most bats tend to roost and hibernate in caves, still many roost in cracks, crevices, and other hard to reach places. Rock climbers recreate on a large array of rock features that are inaccessible or unknown to bat biologists and could serve as a valuable resource in identifying the location of bat species for conservation efforts. Yet, developing and maintaining a productive relationship between recreationists and the conservation community can be challenging, making environmental communication vital to successful collaborative efforts. We explored rock climbers' willingness to participate in a citizen science program for reporting bat sightings through Climbers for Bat Conservation (CBC) while at Red River Gorge (RRG), Kentucky. We utilized a mixed methods case study consisting of a world café facilitated dialog with members of a local climbing organization, bat biologists, land managers, and landowners (n = 18) as well as semi-structured interview data (n = 12) collected at a local climbing festival. Results indicate mutual importance given to bats, climbing, and conservation from world café attendees. Additionally, attendees identified three key parts of a bat observation that would be critical data for rock climbers to report which included presence of a bat, the location, and the climbing route name. Finally, attendees identified having a local climbing ranger or climbing liaison as important to organizing other climbers to submit data. Interview data revealed that the most mentioned barriers to submitting a bat report were awareness of CBC, time, convenience, forgetfulness, fear of route closures, and access to a phone. A discussion follows detailing how this information may be used to further the design and implementation of a citizen science program as well as increase climber engagement at RRG.
Cardiovascular toxicity from therapies for light chain amyloidosis
Authors: Morfino Paolo , Aimo Alberto , Castiglione Vincenzo , Chianca Michela , Vergaro Giuseppe , Cipolla Carlo Maria , Fedele Antonella , Emdin Michele , Fabiani Iacopo , Cardinale Daniela
Published: July 2023

Amyloid light-chain (AL) amyloidosis is a hematological disorder characterized by abnormal proliferation of a plasma cell clone producing monoclonal free light chains that misfold and aggregate into insoluble fibrils in various tissues. Cardiac involvement is a common feature leading to restrictive cardiomyopathy and poor prognosis. Current first-line treatments aim at achieving hematological response by targeting the plasma cell clones, and these have been adapted from multiple myeloma therapy. Patients with AL amyloidosis often exhibit multiorgan involvement, making them susceptible to cancer therapy-related cardiovascular toxicity. Managing AL amyloidosis is a complex issue that requires enhanced knowledge of the cardio-oncological implications of hematological treatments. Future research should focus on implementing and validating primary and secondary prevention strategies and understanding the biochemical basis of oncological therapy-related damage to mitigate cardiovascular toxicity.
Scenarios of the innovative development of education in the context of the Russian economy’s modernization: entrepreneurial universities vs. high-tech universities
Authors: Dvoretskaya Vera V. , Antonova Irina S. , Semenova Galina N. , Belkina Elena N.
Published: July 2023

The article is aimed at identifying the scenarios of the innovative development of education in the context of the Russian economy’s modernization through the opposition of entrepreneurial universities and high-tech universities. The authors conduct a system econometric analysis. The scenario analysis showed that the strategic prospects (optimistic, long-term scenario) of the innovative development of education to support the modernization of the Russian economy through the optimization of universities’ activities require the upgrading of equipment by 982.51% for increasing the research activities to 10269.44% (compared to the threshold), which will bring Russian universities to the 1st place in the QS ranking. In the medium-term period, the share of modern (less than 5 years old) equipment in Russian universities should tend to be 90%. As it is shown by a probable and promising scenario, this will improve the position of the Russian universities in the QS ranking by 6.17%. It is proved that only high-tech universities contribute to the innovative development of education in the context of the Russian economy’s modernization. Therefore, the reduction of state funding of higher education and science makes no sense in Russia, as well as the development of entrepreneurial universities. Instead, the focus should be on the upgrading of university equipment. The originality of this paper lies in a new vision of the prospects for the development of the system of higher education in Russia in the Decade of Science and Technology (2022–2031). This new vision is as follows: for the innovative development of education in the context of the Russian economy’s modernization, it is necessary to refuse the diversification of universities and to achieve their unification, making a choice either in favor of entrepreneurial universities or in favor of high-tech universities.
Review of adult gender transition medications: mechanisms, efficacy measures, and pharmacogenomic considerations
Authors: Sehgal Inder
Published: July 2023

Gender dysphoria is the imparity between a person’s experienced gender and their birth-assigned gender. Gender transition is the process of adapting a person’s sexual characteristics to match their experienced gender. The number of adults receiving sex hormone therapy for gender dysphoria is increasingly and these pharmacotherapies are increasing being prescribed in a general practice setting. The role of hormone therapy is to reverse or reduce physical sexual characteristics of the birth-assigned gender and enhance and build characteristics aligning to the expressed gender and these therapies apply to both transgender and gender nonconforming patients. Recognizing the options and interpreting the effects of gender transition therapies are fundamental to the discussion and treatment of gender dysphoria. This review summarizes pharmacodynamics, comparative dosing, adverse effects, monitoring, and potential pharmacogenetic influence of current pharmacotherapy. These include the use of 17-beta-estradiol, spironolactone, testosterone, GnRH agonists as well as adjunctive phosphodiesterase-5 inhibitors. The article also addresses gaps within the published literature including optimal routes of administration for individual patients, risks of malignancy and dosing reductions as transgender patients age.
Evidence of impaired H-reflex and H-reflex rate-dependent depression in diabetes, prediabetes and obesity: a mini-review
Authors: Kababie-Ameo Rebeca , Gutiérrez-Salmeán Gabriela , Cuellar Carlos A.
Published: July 2023

Diabetes Mellitus is a public health problem associated with complications such as neuropathy; however, it has been proposed that these may begin to develop during prediabetes and may also be present in persons with obesity. Diabetic peripheral neuropathy is the presence of signs and/or symptoms of peripheral nerve dysfunction in people living with diabetes, which increases the risk of developing complications and has a deleterious impact on quality of life. As part of the therapeutic protocol for diabetes, screening tests to identify peripheral neuropathy are suggested, however, there are no recommendations for people with prediabetes and obesity without symptoms such as pain, numbness, or paresthesias. Moreover, clinical screening tests that are usually used to recognize this alteration, such as tendon reflex, temperature sensation, and pressure and vibration perception, might be subjective as they depend on the evaluator’s experience thus the incorrect application of these tests may not recognize the damage to small or large-nerve fibers. Recent evidence suggests that an objective study such as the impairment of the rate-dependent depression of the H-reflex could be used as a biomarker of spinal disinhibition and hence may provide more information on sensorimotor integration.
Insights into immuno-oncology drug development landscape with focus on bone metastasis
Authors: Kähkönen Tiina E. , Halleen Jussi M. , MacRitchie Gary , Andersson Ronnie M. , Bernoulli Jenni
Published: July 2023

Bone is among the main sites of metastasis in breast, prostate and other major cancers. Bone metastases remain incurable causing high mortality, severe skeletal-related effects and decreased quality of life. Despite the success of immunotherapies in oncology, no immunotherapies are approved for bone metastasis and no clear benefit has been observed with approved immunotherapies in treatment of bone metastatic disease. Therefore, it is crucial to consider unique features of tumor microenvironment in bone metastasis when developing novel therapies. The vicious cycle of bone metastasis, referring to crosstalk between tumor and bone cells that enables the tumor cells to grow in the bone microenvironment, is a well-established concept. Very recently, a novel osteoimmuno-oncology (OIO) concept was introduced to the scientific community. OIO emphasizes the significance of interactions between tumor, immune and bone cells in promoting tumor growth in bone metastasis, and it can be used to reveal the most promising targets for bone metastasis. In order to provide an insight into the current immuno-oncology drug development landscape, we used 1stOncology database, a cancer drug development resource to identify novel immunotherapies in preclinical or clinical development for breast and prostate cancer bone metastasis. Based on the database search, 24 immunotherapies were identified in preclinical or clinical development that included evaluation of effects on bone metastasis. This review provides an insight to novel immuno-oncology drug development in the context of bone metastasis. Bone metastases can be approached using different modalities, and tumor microenvironment in bone provides many potential targets for bone metastasis. Noting current increasing interest in the field of OIO, more therapeutic opportunities that primarily target bone metastasis are expected in the future.
Pangenome insights into the diversification and disease specificity of worldwide Xanthomonas outbreaks
Authors: Agarwal Viplav , Stubits Rachel , Nassrullah Zain , Dillon Marcus M.
Published: July 2023

The bacterial genus Xanthomonas is responsible for disease outbreaks in several hundred plant species, many of them economically important crops. In the era of next-generation sequencing, thousands of strains from this genus have now been sequenced as part of isolated studies that focus on outbreak characterization, host range, diversity, and virulence factor identification. However, these data have not been synthesized and we lack a comprehensive phylogeny for the genus, with some species designations in public databases still relying on phenotypic similarities and representative sequence typing. The extent of genetic cohesiveness among Xanthomonas strains, the distribution of virulence factors across strains, and the impact of evolutionary history on host range across the genus are also poorly understood. In this study, we present a pangenome analysis of 1,910 diverse Xanthomonas genomes, highlighting their evolutionary relationships, the distribution of virulence-associated genes across strains, and rates of horizontal gene transfer. We find a number of broadly conserved classes of virulence factors and considerable diversity in the Type 3 Secretion Systems (T3SSs) and Type 3 Secreted Effector (T3SE) repertoires of different Xanthomonas species. We also use these data to re-assign incorrectly classified strains to phylogenetically informed species designations and find evidence of both monophyletic host specificity and convergent evolution of phylogenetically distant strains to the same host. Finally, we explore the role of recombination in maintaining genetic cohesion within the Xanthomonas genus as a result of both ancestral and recent recombination events. Understanding the evolutionary history of Xanthomonas species and the relationship of key virulence factors with host-specificity provides valuable insight into the mechanisms through which Xanthomonas species shift between hosts and will enable us to develop more robust resistance strategies against these highly virulent pathogens.
Ataxia-associated DNA repair genes protect the Drosophila mushroom body and locomotor function against glutamate signaling-associated damage
Authors: Eidhof Ilse , Krebbers Alina , van de Warrenburg Bart , Schenck Annette
Published: July 2023

The precise control of motor movements is of fundamental importance to all behaviors in the animal kingdom. Efficient motor behavior depends on dedicated neuronal circuits – such as those in the cerebellum – that are controlled by extensive genetic programs. Autosomal recessive cerebellar ataxias (ARCAs) provide a valuable entry point into how interactions between genetic programs maintain cerebellar motor circuits. We previously identified a striking enrichment of DNA repair genes in ARCAs. How dysfunction of ARCA-associated DNA repair genes leads to preferential cerebellar dysfunction and impaired motor function is however unknown. The expression of ARCA DNA repair genes is not specific to the cerebellum. Only a limited number of animal models for DNA repair ARCAs exist, and, even for these, the interconnection between DNA repair defects, cerebellar circuit dysfunction, and motor behavior is barely established. We used Drosophila melanogaster to characterize the function of ARCA-associated DNA repair genes in the mushroom body (MB), a structure in the Drosophila central brain that shares structural features with the cerebellum. Here, we demonstrate that the MB is required for efficient startle-induced and spontaneous motor behaviors. Inhibition of synaptic transmission and loss-of-function of ARCA-associated DNA repair genes in the MB affected motor behavior in several assays. These motor deficits correlated with increased levels of MB DNA damage, MB Kenyon cell apoptosis and/or alterations in MB morphology. We further show that expression of genes involved in glutamate signaling pathways are highly, specifically, and persistently elevated in the postnatal human cerebellum. Manipulation of glutamate signaling in the MB induced motor defects, Kenyon cell DNA damage and apoptosis. Importantly, pharmacological reduction of glutamate signaling in the ARCA DNA repair models rescued the identified motor deficits, suggesting a role for aberrant glutamate signaling in ARCA-DNA repair disorders. In conclusion, our data highlight the importance of ARCA-associated DNA repair genes and glutamate signaling pathways to the cerebellum, the Drosophila MB and motor behavior. We propose that glutamate signaling may confer preferential cerebellar vulnerability in ARCA-associated DNA repair disorders. Targeting glutamate signaling could provide an exciting therapeutic entry point in this large group of so far untreatable disorders.
Micro- and macro-changes in early-stage type 2 diabetes mellitus without cognitive impairment: a diffusion tensor imaging (DTI) and surface-based morphometry (SBM) study
Authors: Tang Xiangyong , Chen Yanzi , Tan Hui , Fang Jinzhi , Yu Dafei , Chen Cuimei , Li Xiao , Hu Ziqi , Ding Ling , Zhang Yuzhong
Published: July 2023

Introduction

Brain structure and function changes are considered major brain damages in type 2 diabetes mellitus (T2DM), which likely has a close relationship with cognitive impairment. Many previous studies have shown by using brain structural and functional magnetic resonance imaging (MRI) methods that brain white and gray matter are damaged in T2DM, leading to cognitive impairment. Researches neglected patients of T2DM without cognitive dysfunction might also have brain changes.

Methods

In this study, subjects with early stage T2DM with no cognitive dysfunction were enrolled to detect brain damages using the tract-based spatial statistics analysis (TBSS) method to demonstrate white matter (WM) micro changes and surface-based morphometry (SBM) method to assess cerebral cortex macro changes.

Results

The whole-brain TBSS analysis revealed that there were no statistically significant changes in fractional anisotropy (FA) and mean diffusivity (MD), but the FA declined in some area of cerebral WM (p < 0.1). The SBM results showed no changes in cortical thickness (CT), cortical volume (CV), surface area (SA), and cortical sulcal curve (CSC) between these two groups, but pial local gyration index (LGI) was decreased in the precuneus (−log10, p = −3.327).

Discussion

In conclusion, early stage T2DM patients without cognitive impairment had brain micro and macro structural damages, suggesting the potential use of MRI as an imaging marker to detect brain changes in early stage T2DM, which could not be observed and assessed clinically.
Evaluating cardiac function with chest computed tomography in acute ischemic stroke: feasibility and correlation with short-term outcome
Authors: Bao Jie , Wang Chen , Zhang Yimeng , Su Zhuangzhi , Du Xiangying , Lu Jie
Published: July 2023

Background

The outcomes of patients with acute ischemic stroke (AIS) are related to cardiac function. Cardiac insufficiency can manifest as hydrostatic changes in the lungs. Computed tomography (CT) of the chest is commonly used for screening pulmonary abnormalities and provides an opportunity to assess cardiac function.

Purpose

To evaluate the correlation between hydrostatic lung manifestations on chest CT and cardiac function with its potential to predict the short-term outcome of AIS patients.

Methods

We retrospectively analyzed AIS patients who had undergone chest CT at admission and echocardiogram within 48 h. Morphological and quantitative hydrostatic changes and left ventricular dimensions were assessed using chest CT. Improvement in the National Institutes of Health Stroke Scale (NIHSS) score on the seventh day determined short-term outcomes. Multivariate analysis examined the correspondence between hydrostatic lung manifestations, left ventricular dimension, and left ventricle ejection fraction (LVEF) on echocardiography, and the correlation between hydrostatic changes and short-term outcomes.

Results

We included 204 patients from January to December 2021. With the progression of hydrostatic changes on chest CT, the LVEF on echocardiography gradually decreased (p < 0.05). Of the 204, 53 patients (26%) with varying degrees of hypostatic lung manifestations had less improvement in the NIHSS score (p < 0.05). The density ratio of the anterior/posterior lung on CT showed a significant negative correlation with improvement in the NIHSS score (r = −5.518, p < 0.05). Additionally, patients with a baseline NIHSS ≥4 with left ventricular enlargement had significantly lower LVEF than that of patients with normal NIHSS scores.

Conclusion

Hydrostatic lung changes on chest CT can be used as an indicator of cardiac function and as a preliminary reference for short-term outcome in AIS patients.
A worldwide bibliometric analysis of acromegaly in the past two decades: 1999–2022
Authors: Peng Shuqin , Liu Qi , Teng Yuanyuan , Huang Biling , Liu Ze , Li Mingliu , Liang Jieyu , Zhang Yi , Wang Min
Published: July 2023

Objectives

To conduct a bibliometric analysis to quantify and identify the current status and trends of acromegaly research in the past two decades.

Materials and methods

Articles related to acromegaly that were published from 1999 to 2022 were retrieved through the Web of Science core collection (WoSCC) database. Then, they were imported into VOSviewer and CiteSpace to conduct a visualization analysis of authors, countries, institutions, citation numbers, cocitations, keywords, and references.

Results

A total of 3,909 articles were identified in the study. Among them, the United States made the largest contribution to the field. Moreover, Colao A. was the most prolific author, and the University of Naples Federico II was the institution with the most publications. In addition, the Journal of Clinical Endocrinology and Metabolism was the core journal in the field. High-frequency keywords mainly included “acromegaly,” “GH (Growth Hormone),” “IGH-I (Insulin-Like Growth Factor I),” “pituitary adenomas,” and “octreotide.”

Conclusion

Studies related to acromegaly have shown stable stepwise growth over the past two decades. Interestingly, the research focus after 2016 gradually shifted from the etiology, mechanism, medications for treatment, and complications to improving prognosis and quality of life of patients with acromegaly. The current findings may provide guidance for further research in the field of acromegaly.
Exploiting semantic information in a spiking neural SLAM system
Authors: Dumont Nicole Sandra-Yaffa , Furlong P. Michael , Orchard Jeff , Eliasmith Chris
Published: July 2023

To navigate in new environments, an animal must be able to keep track of its position while simultaneously creating and updating an internal map of features in the environment, a problem formulated as simultaneous localization and mapping (SLAM) in the field of robotics. This requires integrating information from different domains, including self-motion cues, sensory, and semantic information. Several specialized neuron classes have been identified in the mammalian brain as being involved in solving SLAM. While biology has inspired a whole class of SLAM algorithms, the use of semantic information has not been explored in such work. We present a novel, biologically plausible SLAM model called SSP-SLAM—a spiking neural network designed using tools for large scale cognitive modeling. Our model uses a vector representation of continuous spatial maps, which can be encoded via spiking neural activity and bound with other features (continuous and discrete) to create compressed structures containing semantic information from multiple domains (e.g., spatial, temporal, visual, conceptual). We demonstrate that the dynamics of these representations can be implemented with a hybrid oscillatory-interference and continuous attractor network of head direction cells. The estimated self-position from this network is used to learn an associative memory between semantically encoded landmarks and their positions, i.e., an environment map, which is used for loop closure. Our experiments demonstrate that environment maps can be learned accurately and their use greatly improves self-position estimation. Furthermore, grid cells, place cells, and object vector cells are observed by this model. We also run our path integrator network on the NengoLoihi neuromorphic emulator to demonstrate feasibility for a full neuromorphic implementation for energy efficient SLAM.
RNA-binding proteins as a common ground for neurodegeneration and inflammation in amyotrophic lateral sclerosis and multiple sclerosis
Authors: Acosta-Galeana Isabel , Hernández-Martínez Ricardo , Reyes-Cruz Tania , Chiquete Erwin , Aceves-Buendia Jose de Jesus
Published: July 2023

The neurodegenerative and inflammatory illnesses of amyotrophic lateral sclerosis and multiple sclerosis were once thought to be completely distinct entities that did not share any remarkable features, but new research is beginning to reveal more information about their similarities and differences. Here, we review some of the pathophysiological features of both diseases and their experimental models: RNA-binding proteins, energy balance, protein transportation, and protein degradation at the molecular level. We make a thorough analysis on TDP-43 and hnRNP A1 dysfunction, as a possible common ground in both pathologies, establishing a potential link between neurodegeneration and pathological immunity. Furthermore, we highlight the putative variations that diverge from a common ground in an atemporal course that proposes three phases for all relevant molecular events.