bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting Sustainable Agriculture: Approaches for Mitigating Soil Salinity Challenges: A ReviewPromoting Sustainable Agriculture: Approaches for Mitigating Soil Salinity Challenges: A Review
Authors: . Sarita , . Bhupnesh , Goyal Vinod
Published: February 2024

Soil salinity is a major abiotic stress which limits the agricultural productivity throughout the world. Anthropogenic strategies play a vital role in mitigating soil salinity and restoring soil health. These strategies encompass physical, chemical and biological processes, each targeting different aspects of soil salinity management. Physical processes involve the manipulation of soil and water properties to minimize salt accumulation. Improved irrigation techniques, such as drip irrigation and sprinkler systems, optimize water distribution and minimize salt buildup. Efficient drainage systems prevent waterlogging and facilitate salt leaching. Chemical processes focus on modifying the soil environment through amendments, such as gypsum and organic matter additions, to enhance soil structure, nutrient availability and salt displacement. These processes improve soil quality and salt management. Biological processes exploit the capabilities of halophytes, salt-tolerant plant species, to reduce soil salinity by accumulating salts in their tissues. Microbial inoculants or biofertilizers containing beneficial microorganisms enhance nutrient cycling, soil structure and plant tolerance to salinity. The integration of physical, chemical and biological processes offers a comprehensive approach to soil salinity mitigation. By combining these strategies, researchers and practitioners can develop tailored management plans that address site-specific conditions and crop requirements. Successful implementation of anthropogenic strategies can lead to sustainable solutions for soil salinity, improving agricultural productivity and promoting the long-term health of soil ecosystems. This comprehensive review provides insights into the latest research trends and advancements in anthropogenic strategies for mitigating soil salinity, contributing to the development of effective and sustainable approaches for soil salinity management.
Preparation of Gluten Free Cookie using Chestnut and Foxnut Flour Blend: Composition Optimization Through Response Surface Methodology
Authors: Chauhan Divya Singh , Lal Apoorva Behari , Charles Anto Pradeep Raja , Singh Amit Pratap , Khare Ashish , Vashisht Pranav
Published: February 2024

Background: Cookies are baked products that are consumed as a snack worldwide.Gluten, a commonly known protein found in wheat flour, contributes to the extensibility and elasticity of cookie dough. For an individual with aceliac disease, the consumption of gluten should be avoided. In addition, those who observe religious fasts abstain from wheat and wheat-derived items. This study developed gluten-free cookies and studied the impact of chestnut and foxnut flour on its physical, nutritional and sensory properties. Methods: The experimental planning and analysis were performed using the Response Surface Methodology. Two independent variables (foxnut and chestnut flour) were selected and the Central Composite Design was applied. Altogether, thirteen experimental formulations were used for producing cookies. Along with sensory evaluation, the cookies’ moisture, ash, fat and protein contents were examined. For general acceptance, 25-30 semi-trained panelistswere chosen to conduct the sensory analysis based on a numerical scoring test. Result: The sample (S12; 60% chestnut and 5% foxnut flour) had the greatest overall acceptance score. The chemical components of S12, namely moisture, ash, fat and protein, were 3.84%, 3.51%, 18.52% and 6.92%, respectively. Compared to the control sample, S12 was preferredby the panelists.
Teacher professional development and inquiry-based instruction: literature review
Authors: Khalil Eftima , Gunduz Nuket
Published: February 2024

Innovative strategies can revolutionise student learning if implemented properly. Nonetheless, teachers need sufficient training to do this. Therefore, teacher professional development programmes should be reviewed to see if they provide sufficient training for teachers to effectively implement inquiry-based instruction, since it is considered one of these innovative methods. This paper synthesises the existing literature on teacher professional development for inquiry-based instruction from the fields of education and social science between 2001 and 2022. The EBSCO host library, Scopus, Science Direct, ProQuest Dissertations & Theses, Linked Papers, and Taylor & Francis data bases were used for this review. The titles, abstracts, keywords, and publication dates of the selected records were converted into Microsoft Excel, where they were then reviewed to identify the publications that were in line with the scope of the study. A total of 135 studies, including articles and dissertations, were reviewed for this study. The findings of this study provide insight into the gaps in the existing literature on inquiry-based instruction and teacher professional development, as well as suggestions for potential areas for further research.

Keywords: education field; innovative methods; inquiry-based instruction; social studies; teacher development
A Historical and Empirical Review of Compassion
Authors: Walker Mark S. , Wright Lyndsay
Published: February 2024

Compassion is a core attribute of nursing practice and is associated with improved patient satisfaction and outcomes. Only recently has compassion appeared in nursing literature. Therefore, the purpose of this literature review is to examine the historical context of compassion within nursing education and practice, how it is currently defined, and a review of the empirical data. The findings of this review revealed that compassion has been defined in a variety of methods, often based on the discipline in which the term is being defined. However, the empirical evidence attempts to define compassion across disciplines, which may present challenges and, as a result, be wrongly characterized and defined.
Concept of Love in Nursing Based on the Iranian View: Love, True Meaning, or Virtual?
Authors: Ghorbani Azam , Sadat Hoseini Akram Sadat
Published: February 2024

Love is a concept with a special position in human interaction and the definitions of love vary by societies. Also, a common understanding of love in nursing was not located, and very few studies have attempted to describe the concept of love in nursing. This concept analysis aimed to analyze the concept of love in nursing by accounting for the views of scholars and Iranian intellectuals using the seven stages of Meleis’s conceptualization. Based on the perspectives of Iranian intellectuals, the love and affection of nurses toward their patients derive from their love of God. This affection is inherent in nurses and manifests itself during nursing practice. The results indicated that love in nursing is the excessive affection/compassion that nurses have toward their patients and is derived from loving God and nurses’ desire to achieve excellence, which is God. Loving patients leads to nurses’ growth and spiritual development.
Nursing Faculty Well-Being: A Qualitative Study
Authors: Stockmann Cherrill , Ford Nina , Peterson Kate
Published: February 2024

The purpose of this qualitative study was to explore faculty perceptions of nursing faculty well-being (NFWB) and the relationship between NFWB and the nursing faculty shortage. Individual interviews were conducted with a sample of 12 nursing faculty. Data were analyzed using content analysis. The three categories that emerged were NFWB with subcategories multidimensional, enjoyment, supportive work environment, and support from administration; maintaining well-being with subcategories balance and time; and negative effect on well-being with subcategories burnout, lack of support, lack of time, and the COVID-19 pandemic. Participants perceived NFWB as fundamental to their professional roles and their personal lives.
Caring Praxis: Responding to Persons Experiencing Opioid Use Disorder
Authors: Gramling Kathryn Louise , Elliott Kathleen Mary
Published: February 2024

This article ascertains the features of Roach’s Caring Theory in a published educational approach to prepare Doctor of Nursing Practice (DNP) students to care for persons with opioid use disorder and substance use disorder. The intervention documented a positive change in the attitudes of DNP students after a 13-week didactic and experiential program. However, the research design was not grounded in a nursing theory. This secondary study reanalyzed the intervention through the lens of Simone Roach’s Caring model. The aim is to make caring attributes visible in the teaching and learning of caregiving for this population. Roach’s six Cs of compassion, competence, confidence, conscience, commitment, and comportment are illustrated.
Leukemoid Reaction in an Elderly Patient with Aortic Valve Infective Endocarditis and Pancreatic Adenocarcinoma
Authors: Reznik E. V. , Batov M. A. , Aparina T. V. , Kim O. V. , Shurdumova M. Kh. , Mikhaleva L. M. , Smirnov A. P. , Golukhov G. N.
Published: February 2024

Leukemoid reaction (LR) associated with solid tumors has been documented for many decades. LR is often associated with an unfavorable prognosis and aggressive course of the disease. However, the differential diagnosis of LR is of significant difficulty when a patient has several potential etiological factors, each of them individually may cause LR or, on the contrary, lead to a systemic reaction of the body within a single pathogenetic chain.

We present a clinical observation of an elderly patient admitted to the intensive care unit due to the first-time encountered weakness in the right extremities. Clinical and instrumental examination revealed an acute cerebral ischemia with leukocytosis increase up to 60.000 cells/μL with leukocyte formula left shift and subsequent patient decompensation with lethal outcome, despite the intensive treatment.

Autopsy revealed a low-differentiated adenocarcinoma of the pancreatic tail with multiple metastatic lesions in regional lymph nodes and liver, as well as a competing disease — acute infective endocarditis of the aortic valve, which was the cause of sepsis development with septicemia type and thromboembolism both in the great circulation circle with the presence of ischemic cerebral infarction, spleen infarcts, and in the small circle with the development of thromboembolism in the right segmental branches of the pulmonary artery. Given the advanced stage of pancreatic cancer and lack of direct evidence of sepsis at primary diagnosis, paraneoplastic nature of LR is more likely, but infective endocarditis and concomitant pathology also may have contributed to the development of LR.
BRAF Mutations: Oncogenic Drivers in Solid Tumors
Authors: Roa Paola , Bremer Nicole Virginia , Foglizzo Valentina , Cocco Emiliano
Published: February 2024

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.
Safety Responsiveness and Psychological Distress Among Health Care Workers During COVID-19 (2020–2022) in the Pacific Northwest
Authors: Hurtado David A. , Greenspan Samuel A. , Alley Lindsey , Hammer Leslie B. , Furnari Megan , Lenhart Abigail
Published: February 2024

Objectives. The COVID-19 pandemic imposed unprecedented safety challenges on health care facilities. This study examined whether health care workers who deemed a better safety response to the pandemic by their units or employers experienced lower psychological distress.

Methods. Patient care workers at a health care system in the Pacific Northwest were surveyed every 6 to 8 months from May 2020 to May 2022 (n = 3468). Psychological distress was measured with the Well-being Index (range: −2 to 7 points). Safety response was scored on the basis of participants’ ratings (on a 1–5 scale) of equipment sufficiency and responsiveness to safety concerns by their health care system and unit.

Results. Adjusted multilevel regressions showed an inverse association between safety responsiveness and psychological distress at the individual level (b = −0.54; 95% confidence interval [CI] = −0.67, −0.41) and the unit level (b = −0.73; 95% CI = −1.46, −0.01). The cross-level interaction was also statistically significant (b = −0.46; 95% CI = −0.87, −0.05).

Conclusions. Health care workers who deemed a better response to safety challenges reported lower psychological distress. This study highlights the need for continued efforts to ensure adequate safety resources. ( Am J Public Health. 2024;114(S2):S204–S212. https://doi.org/10.2105/AJPH.2024.307582 )
Surgical Management of Intraosseous Neurofibroma in Cervical Spine
Authors: Iwai Chizuo , Nozawa Satoshi , Fushimi Kazunari , Yamada Kazunari , Akiyama Haruhiko
Published: February 2024

Case:

A 30-year-old man had cervical radiculomyelopathy and neck pain caused by a massive intraosseous neurofibroma (IONF) originating from the C6 vertebrae. We performed posterior tumor resection with spinal instrumentation and fusion from C3 to T2 and a follow-up resection procedure of the remaining C6 anterior tumor, sacrificing the affected vertebral artery (VA), which accordingly required bypass surgery at 2 months recovery. Reconstruction using a titanium mesh cage was successfully performed. There were no local recurrences at 2 years postoperatively.

Conclusions:

Total tumor resection split into 2 stages with sacrifice of the affected VA is a feasible option for treatment of IONF.
Communication Ethics in Football Fan Interactions with Blackpink's K-pop Fandom
Authors: Anggraeni Nur Halimah , Adiprabowo Vani Dias
Published: February 2024

Communication between humans can be established more easily and quickly with the development of advanced technology today. The number of social media that exists at this time, makes the communication process can be done easily. Currently, the communication process has become easier so that we know media communication, namely in this study through Instagram social media. In using social media there are communication ethics that must be considered, so it should not be arbitrary in communicating. This study examined the media behavior of football fans on Blackpink's K-pop fandom on Blackpink's Instagram social media account. The research method in this study uses a qualitative approach. Data collection is carried out by observing a case that is happening through Instagram social media. The data collection method used is by observing and analyzing the ethics in communicating football fans with Blackpink's K-pop fandom on Instagram media through comments shown on the blackpinkofficial Instagram account. The results of this study, we can see that the communication we use on Instagram, over time can reduce the rules contained in it. The reason is, social media is a gathering place for various kinds of human nature, both mature in addressing problems and those who are still childish, causing poor communication ethics of football fans and Blackpink fans.
Problematika Mental Illness dan Solusinya dalam al-Qur’an Perspektif Hamka
Authors: Muhammad Hafid Nur , Handayani Ikrimah Retno , Nurrohmah Nina
Published: February 2024

The number of suicide cases in Indonesia, a country where Muslims constitute the majority of the population, has unquestionably surprised some Muslims. In Islam, it is prescribed that people should not take another person's life, especially their own. This research uses a literature approach. The purpose of this research is to explore more deeply about mental illness in Hamka's perspective. In essence, every human being can contract mental illness, the only difference is that not all of these problems end in suicide. It can be concluded that according to Hamka, the center of the phenomenon of mental illness is centered on one condition, namely human closeness to God. Humans who have mental health problems (mental illness) are encouraged to get back to know God who created them, follow all things that are commanded, and stay away from things that are prohibited in the Qur'ān.
الهوى والشهوة في القرآن الكريم: دراسة دلالية
Authors: Suharto Ahmad , Ardana Pamasa , Badrun Muhammad , Pratiwi Mustikasari Intan
Published: February 2024

There is disagreement among scholars since the word "Qur'an" has multiple meanings.  The Qur'anic phrases "Al-Hawa" and "Al-Syahwah" are examples of pairs of synonymous sentences. At first glance, from the perspective of the second language, the lafadz has almost the same meaning, namely love or pleasure. But the Qur'an gives different meanings from the two lafazh. This study aims to find out the original meaning of lafazh Al-Hawa and Al-Syahwah, find out the difference in meaning by examining the contextual meaning of lafazh Al-Hawa and Al-Syahwah in the Qur'an, to reveal the wisdom contained in the Qur'an as a whole. To examine the differences between the words Al-Hawa and Al-Syahwah in the Qur'an, the author uses a descriptive-analysis method and a semantic approach, namely by examining the words Al-Hawa and Al-Syahwah in terms of linguistic differences. From linguistic differences, it can be concluded that al-Hawa is more inclined to opinions or beliefs that are inclined to negative traits because they neglect the perpetrators. While al-Syahwah is more inclined to the senses that have no effect on the body but affect psychological pleasure that is praiseworthy at one time and can be reprehensible at another time.
Metode Menghafal Al-Qur’an untuk Anak Tunalaras dengan Metode Fasih Al-Qur’an (Studi Kasus di Pondok Pesantren Ainul Yakin Yogyakarta)
Authors: Rifaannudin Mahmud , Rizka Syifa' Nadia , Rahman Akbar Ahmad Fadly , Kaulan Maisurah Rezki
Published: February 2024

A unique technique is needed for some people to memorize the Qur'an, especially children who struggle emotionally. Certain techniques designed for Qur'anic memorization are inapplicable to children with impairments. Therefore, understanding the Qur'an requires a unique approach, just as it does for children in general. Ainul Yakin Islamic Boarding School Yogyakarta gives children with disabilities a special method to be applied in memorizing the Qur'an called the "Fasih Al-Qur'an" method. This study aimed to find out the "Fasih Al-Qur'an" method to learn the Qur'an for students with emotional disorders at the Ainul Yakin Islamic Boarding School in Yogyakarta. This research is field research with qualitative research methods. Data collection techniques with three steps observation, interview, and documentation. Field qualitative data processing and analysis techniques using four methods data collection, data reduction, data presentation, and conclusion. The results of this paper show that the method of memorizing the Qur'an for children with disabilities, the "Fasih Al-Qur'an" method is proof of the ease of remembering the Qur'an because the Qur'an is for all humans without any differences, especially children with emotional disorders. Habitual learning in boarding schools makes children accustomed to memorizing the Qur'an, and negative behavior will be reduced.
Karakteristik Rasm dalam Manuskrip Mushḥaf Al-Qur’an KH. Abdul Hamid Chasbullah
Authors: Fithrotul Aini Adrika , Khanin Mahfudzoh Rif’atul , Noorhidayati Salamah
Published: February 2024

One of the Qur'an manuscripts from the 20th century is the written version (mushḥaf) KH. Abdul Hamid Chasbullah. The mushḥaf is evidence of the historical heritage of the ulama of Nusantara who have special attention in the field of copying the Qur'an manuscripts. In this study, the author will examine the general description of the mushḥaf and the characteristics of the rasm by referring to the rules of Sheikh Jalal Al-din Al-Suyuthi in the book Al-Itqan fi Ulum Qur'an. The method that the author uses is qualitative research that leads to library research, by using observation tools, interviews, and documentation of the manuscript. The findings of this study are first, this mushḥaf is kept intact (not scattered) although some sheets have been lost and eaten by termites. This 32.3 x 21 x 7.5(cm) mushḥaf was written for the personal use of the copyist. It can be seen that there aren’t illustration and illumination aspects. Second, from the analysis of surah Al-Baqarah juz 2, the copying of this mushḥaf still adheres to the basics of mixed rules between the rasm utsmani and  imla'i. Likewise, in terms of qira'at, this mushḥaf mostly uses the history of Imam Hafs 'an Ashim, but some words use mixed history.
الاستعارة بين الرماني وسيّد قطب في القرآن الكريم: دراسة مقارنة
Authors: Syahadah Fadhmah , Haji Daud Nadwah
Published: February 2024

This study, Metaphor between Al-Rumani and Sayyid Qutb in the Holy Qur'an: A Comparative Study, compared Sayyid Qutb, a well-known modern writer, with Al-Rumani, an older writer, in order to emphasize the metaphor technique. The study's approach will be twofold: first, it will define the terms "statement" and "metaphor," and then it will adopt an analytical approach by analyzing the metaphor used in the Holy Quran by Al-Ramani and Sayyid Qutb. The study's conclusions and their differences indicate that these two scholars agree that rhetoric—and metaphor in particular—is a crucial component of miracles in the Holy Qur'an. They use various methods and passages from the Holy Qur'an to explain metaphors in different ways.
Wake characteristics of wind-sand cylindrical flow under different turbulence intensity
Authors: Liang ChangPing , Lu Bo , Wang Qing , Guo XingDuo
Published: February 2024

Wind-sand environment has a great influence on wind turbine performance. In order to further investigate the influence of turbulence on wind turbine wake characteristics in wind-sand environment, the gas-solid two-phase numerical simulation was carried out by using SST k-ω turbulence model and MPPICFoam solver based on OpenFOAM to solve the problem of flow around a cylinder. The variation of aerodynamic load on the cylinder surface of clean flow field and wind-sand flow field under different turbulence is compared, and the frequency of vortex shedding is studied by spectrum analysis. Secondly, the particle distribution and the evolution process of the wind-sand flow field are studied. Finally, different wake velocity sections are selected to analyze the influence of different turbulence intensity on the wake velocity of the wind-sand flow field. The results show that wind-blown sand reduces the frequency of wake vortex shedding, while turbulence increases the frequency of wake vortex shedding and reduces the scale of wake vortex. In addition, the wind-sand flow field accelerates in the far wake region, and the increase of turbulence strengthens this phenomenon.
Association between self-perception of genital image in patients diagnosed with endometriosis and chronic pelvic pain and healthy women.
Authors: Palomares Paula Navarro , Boyero Noemí Álvarez , Mohedo Esther Díaz , Herrera María José Suárez
Published: February 2024

Introduction: Endometriosis is a pathology that carries a high social stigma and a factor in the quality of life of the sufferer. Its etiology is unknown and treatment includes surgical and conservative measures, including hormonal suppression.
Objectives: The main objective of the study is to demonstrate a distortion of the genital image in patients diagnosed with endometriosis with chronic pelvic pain, the secondary objective is to associate the distortion of the genital image with the quality of life.
Methodology: A cross-sectional study of cases (women with endometriosis and CPP) and controls (healthy women) were carried out with a total of 284 women over 18 years of age.
Results: Statistically significant differences were obtained in favor of a lower perception of genital self-image and quality of life (for the physical component), in women with endometriosis and CPP, compared to healthy women.
Conclusion: More studies with medium-long term follow-up are needed to be able to make a correct understanding of the process and offer an adequate multidisciplinary approach, aiming at the reconciliation of the idea that the body and the mind are one.
KRAS silencing impacts chromatin organization and transcriptional activity in colorectal cancer cells
Authors: Martins Flávia , Machado Ana Luísa , Ribeiro Andreia , Oliveira Susana Mendonça , Carvalho Joana , Matthiesen Rune , Backman Vadim , Velho Sérgia
Published: February 2024

Preclinical and clinical data have highlighted the challenges in targeting KRAS mutant tumors, revealing that cancer cells initially sensitive to treatment circumvent KRAS dependence and become tolerant. However, the exact mechanisms governing the transition from a drug-sensitive to a drug-tolerant state remain unclear. Herein, we used 3D culture models of mutant KRAS colorectal cancer cells with distinct KRAS dependencies to show that sensitive and resistant cells undergo distinct chromatin and transcriptional adaptations upon acute KRAS loss. KRAS-silenced sensitive cells presented G0/G1 cell cycle arrest and exhibited a transcriptional signature characteristic of quiescent cells. Moreover, proteomic profiling underscored common biological processes up-regulated in sensitive cells, including nucleosome assembly, gene expression regulation, and mRNA splicing. A detailed analysis of chromatin features revealed that sensitive cells altered eu/heterochromatin states and gained TADs after KRAS silencing whereas the eu/heterochromatin states of resistant cells remained unchanged, and the number of TADs decreased. Strikingly, only KRAS-silenced sensitive cells displayed alterations in how chromatin organizes into packing domains, displaying a lower domain packing scaling. Chromatin packing scaling regulates the interaction between macromolecular complexes and DNA, thus controlling transcriptional malleability and plasticity. Accordingly, although KRAS-silenced sensitive and resistant cells displayed a transcriptomic profile distinct from their controls, only sensitive cells presented higher variability over time, thus suggesting higher transcriptional plasticity. Overall, our findings provide compelling evidence supporting chromatin 3D reorganization and transcriptional variability in KRAS-silenced sensitive cells. This epigenetic mechanism is likely to underlie the remarkable ability of cancer cells to adapt, persist, and sustain malignancy without oncogenic KRAS.
Power Generation and Water Conservation Studies in Sudan Canals Using PV Panels
Authors: Abaas Sheikhaldeen N. S. , Naik M. T.
Published: February 2024

The construction of the Grand Ethiopian Renaissance Dam has raised concerns about potential water and energy shortages in Sudan. To address this issue, a scientific paper has proposed installing solar panels on the Al-Jazeera and Al-Mangal irrigation canals in Sudan. This approach aims to prevent clean water evaporation and provide electricity to people living along the canals without the need for extensive transmission lines. The study aims to determine the optimal coverage area for solar panels which will minimize evaporation volume and maximize energy generation without compromising water quality. the installation of solar panels on the two main canals has a potential to generate around 27,000 MW-hr/day of electricity and conserve approximately 70 million mm3 of water per year. The results of this study contribute to the growing body of knowledge supporting the feasibility of using solar panels in developing countries, and emphasize the importance of sustainable energy and water management.
Pedunculopontine-stimulation obstructs hippocampal theta rhythm and halts movement
Authors: Berg Rune , Komi Salif , Dmytriyeva Oksana , Houser Grace , Bonfils Madelaine , Kaur Japreet
Published: February 2024

It is known that movement arrest can be induced by optogenetic stimulation of a brainstem nucleus, the pedunculopontine nucleus (PPN)1–6. This evoked arrest appears conspicuously similar to the freezing behavior often seen as a fear response. Nevertheless, the behavior could also represent a global halting mechanism for movement. This introduces two possible roles of this nucleus: A hub for orchestrating fear-related responses or an omnipotent halting mechanism devoid of emotional components that could, in principle, encompass brain activities other than movement per se. We seek to understand this phenomenon better by engaging the distinct electrical brain activity, the hippocampal theta rhythm7,8. It is prominent during locomotor activity in rodents9–13 and immobile yet vigilant states like freezing14–18. We recorded the hippocampal brain rhythm before and during movement arrest induced by optogenetic stimulation of the PPN in rats. The motor arrest was associated with a clear obstruction of the ongoing theta activity. The timescale of movement arrest was less than 200 ms, similar to the obstruction of the theta rhythm. Since anxiety, fear, and behavioral freezing are associated with hippocampal theta rhythm, which we did not see during PPN stimulation, we suggest that induced motor arrest occurs without an associated emotional component.
A novel pillar-layered MOF with the urea linkers: A capable catalyst for the synthesis of new 1,8-naphthyridines via the anomeric-based oxidation
Authors: Beiranvand Masoumeh , Habibi Davood , Khodakarami Hosein
Published: February 2024

Metal-based catalysts play an essential role in organic chemistry and the chemical industry. In this research, a pillar-layered metal-organic framework (MOF) with the urea linkers, namely Basu-HDI, as a novel and efficient heterogeneous catalyst was designed and successfully synthesized. Various techniques such as FT-IR, EDX, elemental mapping, SEM, XRD, BET, and TGA/DTA studied its structure and morphology. Then, we investigated the synthesis of new 1,8-naphthy-ridines utilizing Basu-HDI in mild conditions via a one‐pot three‐component tandem Knoevenagel/ Michael/cyclization/anomeric-based oxidation reaction. Final products were achieved by anomeric-based oxidation without employing an oxidation agent. Remarkably, this tandem process gave a good range of new 1,8-naphthyridines with high yields in a short reaction time. The pure products were confirmed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry techniques. Moreover, the introduced catalyst showed good efficiency and stability and can be reused four times without significantly reducing efficiency.
SARS-CoV-2 RNA-dependent RNA Polymerase is Linked to Mitochondrial Dysfunction in Mouse Heart
Authors: Naka Kazuhito , Ooshima Akira , Sakaguchi Takemasa , Sotomaru Yusuke , Koike Kanae , Sakamoto Naoya , Ishikawa Tomo-o , Kim Seong-Jin , Sawa Masaaki
Published: February 2024

Little is known about specific viral factors responsible for the pathogenesis and pathophysiology of long COVID1-5. Here we describe a conditional knock-in (cKI) mouse strain inducibly expressing Nsp12, an essential component of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Induction of Nsp12 translation was dependent on co-treatment with inhibitors of the integrated stress response in vitro and in vivo. We show that Nsp12 has a biologically significant link to mitochondrial dysfunction in vivo. In vitro, ectopic Nsp12 expression suppressed mitochondrial function in primary lung epithelial cells isolated from Nsp12 cKI mice. This functionality was physiologically relevant because, although ectopic Nsp12 expression in mouse lungs did not induce pneumonia, it did decrease mitochondrial activity in the hearts of Nsp12 cKI mice over the short and long terms. Administration in vivo of an RdRp inhibitor, EIDD-2801, restored mitochondrial function in cardiomyocytes of Nsp12 cKI mice. Our data demonstrate that SARS-CoV-2 RdRp activity in the lungs leads to cardiac mitochondrial dysfunction in vivo, generating a phenotype resembling aspects of long COVID in humans. Therapeutic targeting of SARS-CoV-2 RdRp may thus represent a novel means of preventing or mitigating intense fatigue and/or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like disease caused by mitochondrial dysfunction in long COVID patients.
Genomic Profiling of Insecticide Resistance in Malaria Vectors: Insights into Molecular Mechanisms.
Authors: Ingham Victoria , Nagi Sanjay
Published: February 2024

Malaria control faces challenges from widespread insecticide resistance in major Anopheles species. This study, employing a cross-species approach, integrates RNA-Sequencing, whole-genome sequencing, and microarray data to elucidate drivers of insecticide resistance in Anopheles gambiae complex and An. funestus. Findings show an inverse relationship between genetic diversity and gene expression, with highly expressed genes experiencing stronger purifying selection. These genes cluster physically in the genome, revealing potential coordinated regulation. We identified known and novel candidate insecticide resistance genes, enriched in metabolic, cuticular, and behavioural functions. We also present AnoExpress, a Python package, and an online interface for user-friendly exploration of resistance candidate expression. Despite millions of years of speciation, convergent gene expression responses to insecticidal selection pressures are observed across Anopheles species, providing crucial insights for malaria vector control. This study culminates in a rich dataset that allows us to understand molecular mechanisms, better enabling us to combat insecticide resistance effectively.
Experimental tests strongly challenge the evidence of a healthy human blood microbiome
Authors: Gloria Leandro Di , Baldi Simone , Curini Lavinia , Bertorello Sara , Nannini Giulia , Cei Francesco , Niccolai Elena , Ramazzotti Matteo , Amedei Amedeo
Published: February 2024

The advent of next-generation sequencing (NGS) technologies has made it doable to investigate the microbial communities in various environments, including all the different human body districts. Hence, the previously established belief of several body sites’ sterilities, including human blood, has now been challenged. However, the metagenomics investigation of habitats with an anticipated low microbial biomass may be susceptible to many and dangerous misinterpretations. Here, we critically evaluate the results of 16S targeted amplicon sequencing performed on the total DNA collected from healthy donors’ blood samples in the light of specific negative controls aimed at addressing potential bias in order to supply the research in this area with trustworthy data. Our negative controls, were prepared by inflating the initial DNA quantity through sequences that can be recognised and subsequently discarded. We found that only three organisms resulted sporadically present among the samples, mostly attributable to bacteria ubiquitous in laboratory reagents. Despite we are not fully able to confirm or deny the existence of healthy blood microbiota, our results strongly suggest that living bacteria, or at least their residual DNA sequences, are not a common and peculiar feature of human blood in healthy people. Finally, our study poses relevant questions on the design of controls in this peculiar research topic in order to avoid spurious results that appear to contaminate current high throughput research.
The clinical efficacy of pegfilgrastim to prevent febrile neutropenia in breast cancer patients receiving docetaxel- cyclophosphamide chemotherapy
Authors: Banno Hirona , Fujii Kimihito , Ohashi Wataru , Saito Masayuki , Ito Yukie , Ido Mirai , Goto Manami , Ando Takahito , Mouri Yukako , Kousaka Junko , Imai Tsuneo , Nakano Shogo
Published: February 2024

Background and aim
: For early-stage breast cancer patients, the myelosuppressive chemotherapy such as docetaxel and cyclophosphamide (TC) chemotherapy are frequently introduced as an adjuvant treatment postoperatively. This regimen is known to develop febrile neutropenia (FN) commonly, therefore a newly developed granulocyte colony-stimulating factor (G-CSF), pegfilgrastim, play an important role in preventing the occurrence of FN. In this study, the clinical advantage of pegfilgrastim during the TC chemotherapy was evaluated by the comparison with the conventional filgrastim.
Patients and method
: A total of 85 patients with stage I or II breast cancer who received TC chemotherapy were divided into the 2 groups, which included: the one that consisted of the patients experienced prophylactic pegfilgrastim administration (named as PEG(+)); the two that consisted of the patients received chemotherapy only with contemporary G-CSF agent, filgrastim that was administered when they suffered from FN or severe neutropenia (named as PEG(-)). This study method was drawn up to evaluate the effectiveness of pegfilgrastim for the prevention of FN and keeping the high relative dose intensity (RDI) (1st endpoint) and to explore whether pegfilgrastim usage might affect the disease-free survival of the patients (2nd endpoint).
Results
The number of the patients that were diagnosed as Grade 3 to 4 “neutrophil count discount” according to common terminology criteria for adverse events version 5.0 was 21 and 6 in PEG(-) and PEG(+), respectively (P = 0.0238). The odds ratio for the onset of “neutrophil count decreased” ranging with Grade 3 to 4 of PEG(+) compared to that of PEG(-) was 0.1143 (95% confidence interval, 0.0175–0.7446). The significant difference of disease-free survival rates of each could not reach the significant level, because the number of events were small.
Conclusion
The administration of pegfilgrastim significantly reduced the risk of development of FN with acceptable adverse events. The chemotherapy RDI of the patients who had prophylactic use of pegfilgrastim was significantly higher than that of the patients who were administered conventional filgrastim by physician’s decision. In this study, we could verify the clinical effectiveness of pegfilgrastim on the patients receiving TC chemotherapy.
A novel Variant in GAS2 Is Associated with Non-Syndromic Autosomal Dominant Hearing Impairment in a Chinese Family
Authors: Zhang Luping , Zheng Danya , Xu Lian , Wang Han , Zhang Shuqiang , Shi Jianhua , Jin Nana
Published: February 2024

Mutation in the GAS2 gene, encoding growth arrest-specific protein 2 (GAS2), causes the disorganization and destabilization of microtubule bundles in supporting cells of the cochlear duct, leading to hearing loss in vivo. The expression and function of GAS2 in cochlear duct is confirmed. However, the molecular mechanism of GAS2 mutant resulting in hearing loss is still unknown. Whole exome sequencing (WES) was employed to identify pathogenic variants. The reverse transcription-PCR was used to show the retention of GAS2 intron 6. The wild-type GAS2 and the truncated GAS2 (mimicking GAS2 variant) were constructed. The protein expression level and cellular localization of GAS2 were checked by Western blots and immunofluorescence staining. The cell apoptosis was assayed by Cell Counting Kit-8 and The DeadEnd™ Fluorometric TUNEL System. We identify a novel heterozygous variant in GAS2 (c.616-2A > G) as the only candidate mutation segregating with late-onset and progressive NSHL in a large dominant family by WES. The mutation causes the retention of intron 6 in mature mRNA and a C-terminally truncated protein (named as GAS2mu) due to an in-frame stop codon (TGA) at c.615 + 109–111 in intron 6. Mechanically, GAS2mu enhances its degradation by ubiquitin-proteasome and displays disorganized microtubule bundles. Additionally, GAS2mu further promotes cell apoptosis by upregulating the ratio of Bcl-xS/Bcl-xL, instead of p53-dependent as wild-type, indicating that GAS2mu acts as a toxic molecule to aggravate cell apoptosis. Our findings demonstrate that the novel variant of GAS2 promotes its protein degradation, microtubule disorganization and cell apoptosis, leading to hearing loss in variant carriers. This study expands the spectrum of GAS2 variants and elucidates the underlying pathogenic mechanisms, which provides a foundation for future investigation of new therapeutic strategies to prevent GAS2-associated progressive hearing loss.
Loss of heterozygosity in CCM2 cDNA revealing a structural variant causing multiple cerebral cavernous malformations
Authors: Riant Florence , Chaussenot Annabelle , Ayrignac xavier , Chatron Nicolas , Riolzyr Terry Granchon , Labauge Pierre , Elisabeth Tournier Lasserve
Published: February 2024

Loss-of-function variants in CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10 genes are identified in the vast majority of familial cases with multiple cerebral cavernous malformations. However, genomic DNA sequencing combined to large rearrangement screening fails to detect a pathogenic variant in 5% of the patients. We report a family with two affected members harboring multiple CCM lesions, one with severe hemorrhages and one asymptomatic. No causative variant was detected using genomic DNA sequencing, CNV detection analysis and RNA sequencing. However, a loss of heterozygosity in CCM2 was observed on cDNA sequences in one of the two affected members, which suggested that this locus might be involved. Whole genome identified a balanced structural variant on chromosome 7 with a breakpoint interrupting the CCM2 gene, preventing normal mRNA synthesis. These data underline the importance of WGS in undiagnosed patients with typical multiple CCM.
Axia: A Home-based Exercise-App with Patient-Education and Self-Management Features - An innovative therapeutic approach for Axial Spondyloarthritis. Results from a Pilot Study.
Authors: Strunz Patrick-Pascal , Maire Maxime Le , Heusinger Tobias , Klein Juliana , Labinsky Hannah , Fleischer Anna , Luetkens Karsten Sebastian , Possler Patricia , Gernert Michael , Leppich Robert , Schmieder Astrid , Hammel Ludwig , Schulz Evelin , Sperlich Billy , Froehlich Matthias , Schmalzing Marc
Published: February 2024

Background
Patients with axial spondyloarthritis (axSpA) benefit from regular home-based exercise (HbE). In spite of recommendations, a relevant proportion of German axSpA patients does not adhere to recommended HbE practices. To enhance HbE care, we developed the novel digital therapeutic (DTx) “Axia” compliant with the European medical device regulation (MDR). Axia offers a modern app-based HbE solution with patient educative content and further integrated features. A first patient survey involved axSpA patients who assessed Axia's efficacy, attractiveness, and functionality through a questionnaire.
Methods
A mixed-method online questionnaire with 38 items was administered to 37 axSpA volunteers after using Axia. Numeric rating scales (NRS) and likelihood scales were primarily used.
Results
Axia received a median rating of 5 out of 5 stars. On NRS scales, Axia scored a median of 9 for intuitiveness and design, and a median of 8 for entertainment. HbE frequency significantly increased from a median of 1 day/week to 6 days/week (p<0.001). Existing HbE practitioners also increased their frequency (median of 4 days/week before, 6 days/week with Axia, p<0.05). 64.9% reported improved range of motion, 43.2% reported reduced pain, and 93.6% enhanced disease-specific knowledge. All users recommended Axia to other patients.
Conclusion
Axia represents a promising DTx for axSpA, warranting further investigation in large randomized controlled interventional trials to establish its efficacy conclusively.
Intestinal methanogen overgrowth (IMO) is associated with delayed small bowel and colonic transit time (TT) on the wireless motility capsule (WMC)
Authors: Talamantes Sarah , Steiner Faye , Spencer Sean , Neshatian Leila , Sonu Irene
Published: February 2024

Background
Methanogens are associated with gut dysmotility in animal models but have not been robustly studied in humans. The WMC assesses regional transit (TT) and pH in the GI tract.
Aims
To study the segmental TT and pH among patients with SIBO or IMO utilizing WMC.
Methods
We conducted a retrospective study of 207 patients who underwent a glucose or lactulose BT and WMC from 2010–2022. Diagnosis of SIBO and IMO were based on the 2017 North American consensus criteria. TT and pH were extracted from WMC recordings. We tested for differences in means of continuous variables and frequencies of categorical variables using two-sample t-tests, Chi-square, and Fisher exact tests. We used R version 3.3.1 (2016-06-21) for all statistical analyses.
Results
A total of 196 patients met criteria, mean age 47.4 years, 155 (79.1%) females. Of the 86 (43.9%) patients with SIBO, 42 (58.3%) had only IMO and 30 (34.9%) met both hydrogen and methane criteria for SIBO. Small bowel TT was longer in patients with IMO compared to negative patients (5h:49min vs 4hr:49min, p = 0.029). Colonic TT was longer in patients with SIBO compared to negative patients (48h:32min vs 39h:25min, p = 0.050). There were no significant differences in segmental pH compared to negative patients.
Conclusions
To our knowledge, this is the largest study of patients who have undergone BT and WMC. SIBO was associated with delayed CTT and IMO with delayed SBTT, but neither with pH. Future investigation is needed to elucidate whether changes in intestinal microbiota affect gut transit.
Research on Historical Value Evaluation and Protection Strategies of Traditional Courtyards in Yulin Ancient City, Shaanxi Province, China
Authors: Ge Xin , Chen Yang , Wang Lu , Chen Yirui
Published: February 2024

Historic towns and traditional houses are an important part of architectural heritage. Heritage has a dual dimension of time and space, the time dimension reflects "historic", the space dimension expresses "regional", is the core value of urban cultural inheritance and sustainable development. At present, most studies on the preservation and renewal of ancient cities are mainly evaluated from the material space or historical dimension, weakening the value analysis from the full cycle time dimension, while the value evaluation system is mainly divided from the material space and weakens the time dimension. At the same time, most of the research focuses on the historical dimension of time, but the present use and future development are often ignored. Therefore, this paper analyzes the value dimension of the whole cycle, uses the literature analysis method to obtain the evaluation content and indicators, adopts the survey questionnaire and surveying and mapping method to evaluate the quantitative value, establishes the historical value evaluation system, and puts forward the classification principle of the historical value of traditional houses and the corresponding protection strategy. In addition, the paper analyzes the use status and space requirements of traditional courtyards, and summarizes the transformation strategies of use value and sustainable value. Finally, a whole-cycle value assessment framework of the ancient city and residential courtyards was formed, protection and renewal strategies were proposed, and case transformation was carried out to provide reference for historical and regional protection in the development of ancient city heritage.