bluuebunny/crossref_metadata_2025 huggingface dataset:
Kureyş’in Batınlarından Benî Mahzûm ve Tarihî Süreçteki Konumu
Authors: YÜKSEL Mücahit
Published: June 2022

Câhiliye döneminde Arap Yarımadası’ndaki hâkim anlayış, asabiyet; bu anlayışın sosyal hayattaki yansıması ise kabilecilik şeklindeydi. İnsanlar, farklı statülerdeki kabilelere mensup olmak zorundaydı. Zira kabile dışında kalan insanın hayatı her an tehlikedeydi. Bu sebeple bölgeye dışarıdan gelen insanlar da ilk etapta mutlaka bir kabilenin himayesine girmenin yolunu aramaktaydı. Nitekim herhangi bir kabilenin liderliğini kabul etmeyen Mekke toplumunda idarî görevlerin paylaşıldığı ve başkanlığın olmadığı görülmektedir. Bununla birlikte Kusay b. Kilâb’ın faaliyetlerinin ardından Kureyş’in belirgin bir ağırlığı göze çarpmaktadır. Benî Mahzûm, Kureyş’e mensup on kabileden biridir. İslâm tarihi kaynakları incelendiği takdirde bu kabileye mensup olan kişilerin, İslâm davetine karşı farklı tepkiler verdikleri görülmektedir. Zira Hz. Peygamber’e düşmanlık yapanlar olduğu gibi ona destek olanlar da mevcuttur. Bu makalede, Benî Mahzûm kabilesinin, câhiliye döneminden başlayarak İslâm sonrası döneme kadarki olaylarda sergilediği tutum ele alınmaktadır. Zira konu, dönemin koşullarının anlaşılması ve İslâm davetinin, kabilecilik anlayışıyla teması açısından önem arz etmektedir. Konunun özelliğine uygun olarak makalede betimleyici, analitik ve tümevarımcı yöntem takip edilmiştir.
CLINICAL FEATURES OF PEMPHIGUS AT NATIONAL HOSPITAL OF DERMATOLOGY AND VENEREOLOGY FROM 2015 TO 2021.
Authors: Phuong Pham Thi Minh , Thao Pham Thi , Trang Trinh Minh
Published: June 2022

Pemphigus is a group of autoimmune disease with several types different in clinical features and histopathology. Objectives: To investigate clinical features of pemphigus in out-patients at National Hospital of Dermatology and Venereology (NHDV). Method: We analyzed retrospectively 279 medical records of out-patients with pemphigus at NHDV from 2015 to 2020. Results: Female accounted for 62.7%. The mean age was 48.3 years old, the youngest was 14 years old and the oldest was 88 years old. The mean age of onset was 46.3 years old, the earliest onset was at 10 and the latest onset was at 88. The mean disease duration was 23.9 months, the shortest was one month and the longest was 20 years. The average hospitalization was 1.54, there was a case hospitalized 10 times. Pemphigus vulgaris accounted for the highest rate of 85.3%, the following was pemphigus erythema (10%). Pemphigus vegetans took the lowest rate of 0.4%. 83.4% of cases having lesions on both normal and seborrheic skin. 56.1% of cases were not affected at mucous membranes while only 4.4% of them free from lesions on the skin. Pemphigus vulgaris was highly developed lesions at mucosal areas more than other types. Moderate pemphigus accounted for the major cases of 68.4%. 14.1% was severe pemphigus. Mono-therapy with corticoid was the most common of (65.1%). A combination regime of corticoid and azathioprine took 12.9%. Notably, there was 3.3% having traditional treatments with herbs. Conclusions: Female accounted for 62.7%. The mean age was 48 years old; the mean age of onset was 46 years olds. Pemphigus vulgaris was the most common type and highly developed lesions at mucous membranes more than other types. Two-third suffered from moderate pemphigus. Mono-therapy with corticoid was seen the most.
COMPARATION OF THE EFFICACY OF ORAL IVERMECTIN COMBINED TOPICAL METRONIDAZOL 1% WITH ORAL AND TOPICAL METRONIDAZOL IN THE TREATMENT OF DEMODICOSIS
Authors: Van Tran Cam , Thu Tran Thi
Published: June 2022

Objectives: To compare the treatment outcomes of pityriasis folliculitis by combining oral ivermectin with topical metronidazol 1% and combining oral with topical metronidazol therapy.

Method: 70 patients with pityriasis folliculitis were randomly divided into 2 groups: 35 patients in group one were treated with oral ivermectin (one dose of 200 µg/kg) and topical metronidazol 1%. 35 patients in group two were treated with oral metronidazol (doses 500 mg per day for 2 weeks) and topical metronidazol 1%. Demodex was detected by standardized skin surface biopsy. The  subjects were followed-up at week 2 and 4 after the treatment.

Result: After 2 and 4 weeks of the treatment, pruritus, red papules, red patchs and skin scabs in both groups reduced. There was no differences between the two groups regarding age, sex and duration of the condition (p> 0.05). Group one had greater reductions in Demodex density than those in the group two (p < 0.05). Moreover, at week 4, the group one treated with oral ivermectin and topical metronidazol, 80% had good improvement, 14.3%:moderate improvement and 5.7%: mild improvement. Meanwhile, in the group treated by combining oral and topical metronidazol, the rates were 71.4%, 22.9% and 5.7%, respectively. The outcomes of the treatment in both groups had no significant difference (p > 0.05). Side effects including pruritus, burning in group one were lower than that of group two (p < 0.05).

Conclusion: There were no differences in clinical improvement in the two groups treated by two different therapies. However, the reductions of the number of Demodex in the group one were higher than those in the group two. On the other hand, the side effects in the group one were less than those in the group two
BỆNH TUYẾN GIÁP TỰ MIỄN VÀ CÁC YẾU TỐ LIÊN QUAN TRÊN BỆNH NHÂN BẠCH BIẾN TẠI BỆNH VIỆN DA LIỄU TP.HCM
Authors: Nguyễn Thị Thanh Huyền  , Nguyễn Trọng Hào
Published: June 2022

Mục tiêu: Xác định tỉ lệ bệnh tuyến giáp tự miễn và các yếu tố liên trên bệnh nhân bạch biến tại bệnh viện Da Liễu TP.HCM từ tháng 9/2020 đến tháng 5/2021.
Đối tượng và phương pháp: Nghiên cứu mô tả cắt ngang trên 120 bệnh nhân tại Bệnh viện Da Liễu TP.HCM trong thời gian nghiên cứu. Tình trạng bệnh tuyến giáp tự miễn được chẩn đoán bằng xét nghiệm chức năng tuyến giáp (TSH) và các tự kháng thể kháng tuyến giáp (TPOAb, TRAb).
Kết quả: tuổi bệnh nhân từ 4 đến 78, với nữ giới chiếm ưu thế. Tuổi khởi phát bệnh là 32,50 (KTPV: 18 – 47,75) và thời gian bệnh là 2 năm (KTPV: 0,92 – 5,00). Tỉ lệ bệnh tuyến giáp tự miễn là 7,5%, tăng tự kháng thể TPOAb và TRAb lần lượt là 20,00% và 10,83%. TPOAb có mối liên quan với các đặc điểm bệnh bạch biến: vị trí khởi phát thương tổn vùng tay, thương tổn tam sắc, diện tích tổn thương da (BSA). Đối với TRAb, có mối liên quan với các đặc điểm: giới tính và thương tổn tam sắc.
Kết luận: Tình trạng tăng tự kháng thể kháng tuyến giáp và bệnh tuyến giáp tự miễn ở bệnh nhân bạch biến trong nghiên cứu tương đồng với các nghiên cứu khác trên thế giới. Có mối liên quan giữa tình trạng tăng tự kháng thể kháng tuyến giáp với giới tính, vị trí thương tổn khởi phát vùng tay, thương tổn tam sắc, diện tích tổn thương da.
Differences of Subjective Well-Being in European Long-term Care Regimes
Authors: Fekete Márta , Patyán László , Hüse Lajos , Huszti Éva , Takács Péter
Published: June 2022

Introduction: With the increase of life expectancy, the issue of quality of life (QoL) for the elderly is getting more focus. Beside the individual view, social and economic aspects are becoming more pronounced. Aims: In this study, we set out to establish a new classification of long-term care (LTC) regimes by examining the relationship between care systems and subjective quality of life. Methods: Our work was based on data from the Survey of Health, Ageing and Retirement in Europe through a secondary analysis of CASP-12 results. It was assumed that higher quality of life values could be observed in countries providing a higher standard of social care. We studied the background variables in different LTC regimes. Results: The data shows that the development and availability of care systems have a significant indirect correlation with older people’s subjective well-being. Our results raise the possibility of a new subdivision of care regimes. Conclusions: Those countries featured earlier as family-based systems and Central-Eastern European countries were growing closer to each other in this classification. As our statistical method proved, family-based and Central-Eastern European regimes are not significantly different (Minimisers). Northern countries, where investment and quality of life are also high, remain highly positioned on the scale (Maximisers). Countries that have medium-level investments and subjective well-being parameters place in the middle of the scale (Optimisers). Global changes (climate, migration, political culture, technology) are expected to have an effect on social care regimes, especially on Minimisers, where the realization or failure of investments is a critical question.
Dementia in Czechia: Prevalence Estimations Until 2050
Authors: Svacinova Kornélia , Pechholdova Markéta
Published: June 2022

Introduction: The Czechia is facing population aging. The number of people with dementia is increasing. Conflicting conclusions of European studies confirm the difficulties of quantifying the disease. Aims: We aim to estimate the number of people with dementia in Czechia until 2050: a) projecting dementia prevalence using prevalence rates from EURODEM and EuroCoDe studies, b) projecting dementia based on mortality tables of individuals living with dementia. Comparing both approaches to dementia estimation. Methods: We conducted a literature review. The projection is based on socio-demographic and health variables; construction of life tables for people with dementia. Results: According to the results a) projecting the prevalence of dementia; over 300,000 seniors aged 60+ will suffer from dementia by 2050; b) estimating the number of individuals living with dementia: The number of men and women with dementia aged 65+ was estimated at over 120 thousand. Conclusions: Czech society is not prepared for this intense increase in the number of individuals living with dementia. We argue early diagnosis as well as appropriate health and social care are urgent.
Targeting the Needs of Self-Determination Theory: An Overview of Mental Health Care Apps
Authors: Brownlow Luke
Published: June 2022

Introduction: Smartphone apps are a highly accessible tool to supplement self-treatment for mental health challenges, such as depression, and are underrepresented in research. While many studies have performed content analyses of health apps, few studies have reviewed their adherence to behavior theory. Aims: The objective of this study is to assess mHealth depression apps through the lens of the Self-Determination Theory and identify if app functions target the three basic needs: autonomy, competence, and relatedness. Methods: All depression apps available from iTunes and Google Play that met inclusion criteria were analyzed (N = 194). Apps were reviewed for price options, store availability, download rates, and how functions targeted the three basic needs for intrinsic and sustained health behavior change outlined in the Self-Determination Theory. Results: Findings showed that most of the apps targeted at least one of the basic needs (158/194, 81.4%). However, only a few of these apps targeted all three basic needs to some degree (15/194, 7.7%), and no single app targeted all three basic needs fully. Furthermore, neither store availability, price option nor download rates were accurate predictors that apps targeted the three basic needs. Conclusions: The results suggest that some depression apps targeted autonomy, competence, and relatedness but this was limited to a small number of apps through few functions available in each app. People who want access to more functions targeting the needs would need to download a suite of apps.
Structural Assessment of the Sustainability of the Historical Clock Tower as a Landmark
Authors: Özkaynak Merve , Şeker Burçin Şenol
Published: June 2022

In the historical process, many tools have been used to measure time. With technological advances, clock towers were built with mechanical clocks. But today, rather than their original function, historic urban centers have become an image of cities. First built in Europe, clock towers were built in various cities of Anatolia during the Ottoman Period. The protection and sustainability of clock towers, which are one of physical identity, is important for the continuity of cultural heritage. Determining the damages that earthquakes will contribute to the protection and sustainability of clock towers. In the study, the historical clock tower in Çorum was modeled in three dimensions and subjected to static and dynamic analysis. In static analysis, it is seen that the upper part of the main entrance door and dynamic analyses increase in the transition from the octagonal plan in the lower region to the circular cross-sectional zone in the upper region. Also, it was determined that the maximum values of deformations appeared as displacement in orthogonal directions at the top of the tower. As a result, as a strengthening proposal, it is thought that iron tensioners passing through the stirrup plane of the entrance door conveyor belt should be added.
Flagship Projects and Socio-Spatial Inequalities. The Case of the Post Refugee Urban Neighbourhood in Kallithea, Attica, Greece
Authors: Tousi Evgenia
Published: June 2022

The issue of flagship projects is becoming more and more timely in the contemporary globalized urban context. The overall transformation of a former decayed urban enclave through a well targeted large-scale intervention is found in many cities around the world. Following the narrative of Bilbao, which is considered to be a success story, many cities attempted to imitate the “Bilbao effect”. Taking into account the international experience on the field, this paper tries to analyze a Greek example, delving into the specificities of time and space. The selected case study could be considered as one of the first flagship or prestige projects in Greece and is strongly associated with the concept of “Athenian Riviera”, a metropolitan coastal zone that is currently under urban regeneration. This prestige project is located inside a former refugee enclave that has until today a significant number of old refugee housing complexes, constructed around 1930. The stark contradiction between the iconic building and the derelict neighboring refugee apartments reflects clearly the impact of site-specific urban interventions; they widen the gab between upgraded and degenerated enclaves inside the city. The presence of vulnerable households in the area raises concerns on future gentrification procedures. Field work combined with literature review is being made so as to adumbrate the crucial issues in the area of study. Photographic documentation and cartographic depiction are used as tools so as to illustrate the physiognomy of the area. The ultimate purpose of the paper is to address the issue of socio-spatial inequalities in the era of globalization, where the implementation of place branding strategies puts aside certain social factors, leading to spatial segregation between degraded and upgraded areas.
Urban Acupuncture as a Method of Open Space Regeneration in Greek Ex-Refugee Areas. The Case of Nikea, Piraeus
Authors: Tousi Evgenia , Sinou Maro , Perouli Antonia
Published: June 2022

The paper explores the potential of implementing the principles of urban acupuncture in a selected Greek case study, taking into account international experience in the field. The research includes literature review and field work. The area of study is Nikea, an ex-refugee urban area in the Attica metropolitan region. It was founded during the 1930s to host refugees from Asia Minor. The initial Hippodamian grid offers beneficial intermediate communal spaces inside each city block and there are also larger green spaces in proximity.  However, the area suffers from urban blight owed largely to the poor quality of preservation of the old refugee housing estates. A mixture of factors contributes to the complex contemporary situation characterized by opportunities and challenges. On the one hand, there is great potential for regenerating the existing intermediate communal spaces and on the other decaying refugee houses and vulnerable households intricate the already convoluted situation. The paper provides cartographic depiction and categorization of the existing open  spaces highlighting also contemporary socio-spatial challenges and market driven limitations. The research describes the obstacles that hinder the activation of “urban sensitive points” in terms of urban acupuncture, also advocating for possible solutions.  The paper opens dialogue on the Greek case study in terms of urban acupuncture with the view to suggest strategies to foster socio-spatial cohesion in degraded ex -refugee urban areas. This is a pilot case study with further application in other post-refugee urban areas in Greece that share common socio-spatial attributes. Thus, the topic of the paper may have a greater impact within the Greek urban context.
Avaliação do status de conservação de Collembola (Hexapoda, Arthropoda) no Brasil
Authors: Silva Clécio Danilo Dias da , Santos Daniele Bezerra dos
Published: June 2022

Este trabalho teve como objetivo analisar e discutir aspectos relacionados ao status de conservação da classe Collembola, com ênfase na ordem Entomobryomorpha. Verificou-se  que as ordens Entomobryomorpha (n=144), e Poduromorpha (n=110) são as mais representativas com relação ao número de espécies avaliadas, seguidas de Symphypleona (n=54), e Neelipleona (n=02). No que diz respeito a Entomobryomorpha, estão listadas um total de 312 espécies. Essas foram maiormente avaliadas nas categorias da International Union for Conservation of Nature (IUCN), respectivamente, em Pouco Preocupante – LC (n=139), Dados Insuficientes – DD (n=09), Vulnerável – VU (n=03), Criticamente Ameaçada – CR (n=02) e Não Aplicável – NA (n=01). Os dados analisados evidenciam a necessidade de mais estudos e investigações no entono da taxonomia, ecologia e conservação para o grupo, principalmente, quando levados em considerações o ínfimo número de especialistas e o elevado número de espécies a serem descritas no Brasil e no Mundo.
A rare case of pure-type embryonal carcinoma in a 75-year-old woman mimicking epithelial ovarian carcinoma
Authors: Jo Hyun Been , Kim Eun Taeg , Lee Nam Kyung , Choi Kyung Un , Kim Eon Jin , Shin Yun Joo , Kim Ki Hyung , Suh Dong Soo
Published: June 2022

Embryonal carcinoma, a very rare ovarian germ cell tumor, involves pure and mixed phenotypes. Pure-type embryonal carcinoma has never been reported in postmenopausal women. The current case was, thus, misdiagnosed as an epithelial ovarian carcinoma based on radiologic findings. Herein, we describe the case of ovarian embryonal carcinoma in a 75-year-old woman along with a literature review. Magnetic resonance imaging findings were suggestive of epithelial ovarian malignancy associated with endometrioma, including ureteral invasion. The patient underwent complete surgical staging, and a pathologic diagnosis of pure-type embryonal carcinoma was made. The patient’s postoperative course was uneventful, and adjuvant chemotherapy was administered. Embryonal carcinoma in the postmenopausal woman is a clinical challenge owing to the possibility of its misdiagnosis as epithelial ovarian carcinoma. To the best of our knowledge, this is the first report of pure-type ovarian embryonal carcinoma in a postmenopausal woman, with a description of the clinicopathologic characteristics and review of the relevant literature.
The Effect of Psychoeducational Stress Management Interventions on Students Stress Reduction: Systematic Review
Authors: Bani Ahmad Talal , Meric Meltem , Ayasrah Mohammad
Published: June 2022

Students can be a vulnerable group for stress. A psycho-educational program is one of the strategies to facilitate students’ adjustment and manage stress. This systematic review will integrate the effects of psychoeducational interventions on the level of stress among students. Pubmed, CINAHL, Science Direct Scopus databases were used to find potentially relevant published articles. The title and abstracts are used firstly to screen studies using inclusion and exclusion criteria before going to the next stage of the reviewing of complete articles. A total of eleven articles were selected based on inclusion and exclusion criteria. All articles in this sample were assessed using an instrument to assess overall quality. Study setting, sample size, study interventions, outcome measure/methods of delivery, and results were assessed and extracted. In all of the studies reviewed, the intervention groups experienced significantly greater reductions in perceived stress and symptoms of anxiety and depression. Our review highlights the importance of stress management programs, and the findings from this systematic review indicated that these programs were generally effective for optimizing the stress process and improving coping capacity with stressors.
When in Rome, Not All International Students Do as the Romans Do. A Survey-based Typification of International Students’ Experiences and Profiles at Sapienza University of Rome
Authors: Norton Laura , Giudici Cristina , Fatigante Marilena , Zucchermaglio Cristina
Published: June 2022

Universities often consider international students as a homogeneous group, that is of value for internationalisation purposes. Yet, migratory paths, cultural encounters, motivations and expectations make the experience of these students much varied and highly differentiated. Acknowledging this diversity allows to go beyond aggregate statistics and to assess specific needs and constraints. The present study focuses on the Italian context, introducing a quali-quantitative survey developed to investigate the variety of experiences and profiles of international students enrolled at Sapienza University of Rome. An analysis of multiple correspondence was applied to the survey’s responses. Results were triangulated with qualitative data collected in previous steps of the research, confirming the reliability of the survey and its capacity to discriminate different profiles. Three groups were identified (the «transnational migrants», the «international students», and the «invisible» ones), revealing a series of specificities, and a particular group as most vulnerable. Results are discussed highlighting the need to implement inclusive policies.
Distinct representation of cue-outcome association by D1 and D2 neurons in the ventral striatum’s olfactory tubercle
Authors: Martiros Nuné , Kapoor Vikrant , Kim Spencer E , Murthy Venkatesh N
Published: June 2022

Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory input to the ventral striatal olfactory tubercle (OT) and its convergence with dense dopaminergic input to the OT could underlie this privileged form of associative memory, but how this process occurs is not well understood. We imaged the activity of the two canonical types of striatal neurons, expressing D1- or D2-type dopamine receptors, in the OT at cellular resolution while mice learned odor-outcome associations ranging from aversive to rewarding. D1 and D2 neurons both responded to rewarding and aversive odors. D1 neurons in the OT robustly and bidirectionally represented odor valence, responding similarly to odors predicting similar outcomes regardless of odor identity. This valence representation persisted even in the absence of a licking response to the odors and in the absence of the outcomes, indicating a true transformation of odor sensory information by D1 OT neurons. In contrast, D2 neuronal representation of the odor-outcome associations was weaker, contingent on a licking response by the mouse, and D2 neurons were more selective for odor identity than valence. Stimulus valence coding in the OT was modality-sensitive, with separate sets of D1 neurons responding to odors and sounds predicting the same outcomes, suggesting that integration of multimodal valence information happens downstream of the OT. Our results point to distinct representation of identity and valence of odor stimuli by D1 and D2 neurons in the OT.
All-atom molecular dynamics simulations of Synaptotagmin-SNARE-complexin complexes bridging a vesicle and a flat lipid bilayer
Authors: Rizo Josep , Sari Levent , Qi Yife , Im Wonpil , Lin Milo M
Published: June 2022

Synaptic vesicles are primed into a state that is ready for fast neurotransmitter release upon Ca2+-binding to Synaptotagmin-1. This state likely includes trans-SNARE complexes between the vesicle and plasma membranes that are bound to Synaptotagmin-1 and complexins. However, the nature of this state and the steps leading to membrane fusion are unclear, in part because of the difficulty of studying this dynamic process experimentally. To shed light into these questions, we performed all-atom molecular dynamics simulations of systems containing trans-SNARE complexes between two flat bilayers or a vesicle and a flat bilayer with or without fragments of Synaptotagmin-1 and/or complexin-1. Our results need to be interpreted with caution because of the limited simulation times and the absence of key components, but suggest mechanistic features that may control release and help visualize potential states of the primed Synaptotagmin-1-SNARE-complexin-1 complex. The simulations suggest that SNAREs alone induce formation of extended membrane-membrane contact interfaces that may fuse slowly, and that the primed state contains macromolecular assemblies of trans-SNARE complexes bound to the Synaptotagmin-1 C2B domain and complexin-1 in a spring-loaded configuration that prevents premature membrane merger and formation of extended interfaces, but keeps the system ready for fast fusion upon Ca2+ influx.
On demand expression control of endogenous genes with DExCon, DExogron and LUXon reveals differential dynamics of Rab11 family members
Authors: Gemperle Jakub , Harrison Thomas S , Flett Chloe , Adamson Antony D , Caswell Patrick T
Published: June 2022

CRISPR technology has made generation of gene knock-outs widely achievable in cells. However, once inactivated, their re-activation remains difficult, especially in diploid cells. Here, we present DExCon (Doxycycline-mediated endogenous gene Expression Control), DExogron (DExCon combined with auxin-mediated targeted protein degradation), and LUXon (light responsive DExCon) approaches which combine one-step CRISPR-Cas9-mediated targeted knockin of fluorescent proteins with an advanced Tet-inducible TRE3GS promoter. These approaches combine blockade of active gene expression with the ability to re-activate expression on demand, including activation of silenced genes. Systematic control can be exerted using doxycycline or spatiotemporally by light, and we demonstrate functional knock-out/rescue in the closely related Rab11 family of vesicle trafficking regulators. Fluorescent protein knock-in results in bright signals compatible with low-light live microscopy from monoallelic modification, the potential to simultaneously image different alleles of the same gene, and bypasses the need to work with clones. Protein levels are easily tunable to correspond with endogenous expression through cell sorting (DExCon), timing of light illumination (LUXon), or by exposing cells to different levels of auxin (DExogron). Furthermore, our approach allowed us to quantify previously unforeseen differences in vesicle dynamics, transferrin receptor recycling, expression kinetics, and protein stability among highly similar endogenous Rab11 family members and their colocalization in triple knock-in ovarian cancer cell lines.
Evolutionary convergence of a neural mechanism in the cavefish lateral line system
Authors: Lunsford Elias T , Paz Alexandra , Keene Alex C , Liao James C
Published: June 2022

Animals can evolve dramatic sensory functions in response to environmental constraints, but little is known about the neural mechanisms underlying these changes. The Mexican tetra, Astyanax mexicanus, is a leading model to study genetic, behavioral, and physiological evolution by comparing eyed surface populations and blind cave populations. We compared neurophysiological responses of posterior lateral line afferent neurons and motor neurons across A. mexicanus populations to reveal how shifts in sensory function may shape behavioral diversity. These studies indicate differences in intrinsic afferent signaling and gain control across populations. Elevated endogenous afferent activity identified a lower response threshold in the lateral line of blind cavefish relative to surface fish leading to increased evoked potentials during hair cell deflection in cavefish. We next measured the effect of inhibitory corollary discharges from hindbrain efferent neurons onto afferents during locomotion. We discovered that three independently derived cavefish populations have evolved persistent afferent activity during locomotion, suggesting for the first time that partial loss of function in the efferent system can be an evolutionary mechanism for neural adaptation of a vertebrate sensory system.
Effect of plyometric training and neuromuscular electrical stimulation assisted strength training on muscular, sprint, and functional performances in collegiate male football players
Authors: Hasan Shahnaz , Kandasamy Gokulakannan , Alyahya Danah , Alonazi Asma , Jamal Azfar , Iqbal Amir , Unnikrishnan Radhakrishnan , Muthusamy Hariraja
Published: June 2022

Background

The study’s objective was to analyze the influence of an 8-week neuromuscular electrical stimulation (NMES) with a plyometric (PT) and strength training (ST) program on muscular, sprint, and functional performances in collegiate male football players.

Methods

Sixty collegiate male football players participated in this randomized controlled trial single-blind study. All the participants were randomly divided into two groups: (1) NMES group (Experimental, n = 30) who received NMES assisted ST and (2) sham NMES group (Control, n = 30) who received sham NMES assisted ST. In addition, participants from both groups received a PT program; both groups received intervention on three days a week for 8-weeks. The study’s outcomes, such as muscular, sprint, and functional performances, were assessed using a strength test (STN) for quadriceps muscle, sprint test (ST), and single-leg triple hop test (SLTHT), respectively, at baseline pre-intervention and 8-week post-intervention. The interaction between group and time was identified using a mixed design (2 × 2) ANOVA.

Results

Significant difference found across the two time points for the scores of STN: F (1.58) = 5,479.70, p < 0.05; SLTHT: F (1.58) = 118.17, p < 0.05; and ST: F (1.58) = 201.63, p < 0.05. Similarly, the significant differences were found between groups averaged across time for the scores of STN: F (1.58) = 759.62, p < 0.05 and ST: F (1.58) = 10.08, p < 0.05. In addition, after 8-week of training, Cohen’s d observed between two groups a large to medium treatment’s effect size for the outcome STN (d = 10.84) and ST (d = 1.31). However, a small effect size was observed only for the SLTHT (d = 0.613).

Conclusions

Findings suggest that the effect of PT and ST with either NMES or sham NMES are equally capable of enhancing muscular, sprint, and functional performances in collegiate male football players. However, PT and ST with NMES have shown an advantage over PT and ST with sham NMES in improving muscular performance and sprint performance among the same participants.
Changes in Optic Nerve Head and Retinal Morphology During Spaceflight and Acute Fluid Shift Reversal
Authors: Pardon Laura P. , Macias Brandon R. , Ferguson Connor R. , Greenwald Scott H. , Ploutz-Snyder Robert , Alferova Irina V. , Ebert Doug , Dulchavsky Scott A. , Hargens Alan R. , Stenger Michael B. , Laurie Steven S.
Published: June 2022

Importance

Countermeasures that reverse the headward fluid shift experienced in weightlessness have the potential to mitigate spaceflight-associated neuro-ocular syndrome. This study investigated whether use of the countermeasure lower-body negative pressure during spaceflight was associated with changes in ocular structure.

Objective

To determine whether changes to the optic nerve head and retina during spaceflight can be mitigated by brief in-flight application of 25-mm Hg lower-body negative pressure.

Design, Setting, and Participants

In the National Aeronautics and Space Administration’s “Fluid Shifts Study,” a prospective cohort study, optical coherence tomography scans of the optic nerve head and macula were obtained from US and international crew members before flight, in-flight, and up to 180 days after return to Earth. In-flight scans were obtained both under normal weightless conditions and 10 to 20 minutes into lower-body negative pressure exposure. Preflight and postflight data were collected in the seated, supine, and head-down tilt postures. Crew members completed 6- to 12-month missions that took place on the International Space Station. Data were analyzed from 2016 to 2021.

Interventions or Exposures

Spaceflight and lower-body negative pressure.

Main Outcomes and Measures

Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness.

Results

Mean (SD) flight duration for the 14 crew members (mean [SD] age, 45 [6] years; 11 male crew members [79%]) was 214 (72) days. Ocular changes on flight day 150, as compared with preflight seated, included an increase in minimum rim width (33.8 μm; 95% CI, 27.9-39.7 μm; P < .001), decrease in cup volume (0.038 mm3; 95% CI, 0.030-0.046 mm3; P < .001), posterior displacement of Bruch membrane opening (−9.0 μm; 95% CI, −15.7 to −2.2 μm; P = .009), and decrease in macular thickness (fovea to 500 μm, 5.1 μm; 95% CI, 3.5-6.8 μm; P < .001). Brief exposure to lower-body negative pressure did not affect these parameters.

Conclusions and Relevance

Results of this cohort study suggest that peripapillary tissue thickening, decreased cup volume, and mild central macular thinning were associated with long-duration spaceflight. Acute exposure to 25-mm Hg lower-body negative pressure did not alter optic nerve head or retinal morphology, suggesting that longer durations of a fluid shift reversal may be needed to mitigate spaceflight-induced changes and/or other factors are involved.
Exploring the genetic space of the DNA damage response for cancer therapy through CRISPR‐based screens
Authors: Wilson Jordan , Loizou Joanna I.
Published: June 2022

The concepts of synthetic lethality and viability have emerged as powerful approaches to identify vulnerabilities and resistances within the DNA damage response for the treatment of cancer. Historically, interactions between two genes have had a longstanding presence in genetics and have been identified through forward genetic screens that rely on the molecular basis of the characterized phenotypes, typically caused by mutations in single genes. While such complex genetic interactions between genes have been studied extensively in model organisms, they have only recently been prioritized as therapeutic strategies due to technological advancements in genetic screens. Here, we discuss synthetic lethal and viable interactions within the DNA damage response and present how CRISPR‐based genetic screens and chemical compounds have allowed for the systematic identification and targeting of such interactions for the treatment of cancer.
Policy search for active fault diagnosis with partially observable state
Authors: Král Ladislav , Punčochář Ivo
Published: June 2022

The article deals with a novel design of an active fault detector (AFD) for a nonlinear stochastic system with a partially observable state. The imperfect state information problem is converted to a perfect state information problem using a state estimator. Subsequently, the problem is decomposed into separate tasks of an optimal fault detector design and an approximate input generator design using a dynamic programming technique. While the former task is straightforward, the latter represents a nonlinear functional optimization problem. The input generator is approximated by a multi‐layer perceptron neural network, and its unknown parameters are found using the policy search method. Effectiveness of the proposed AFD design is demonstrated numerically on a pendulum system and a heating/cooling system.
Insight into the Effects of Current Collectors and In Situ Ni Leaching in High‐Voltage Aqueous Supercapacitors
Authors: Yu Jinhe , Yu Chang , Guo Wei , Wang Zhao , Ding Yiwang , Xie Yuanyang , Liu Kunlun , Wang Hui , Tan Xinyi , Huang Huawei , Qiu Jieshan
Published: June 2022

The limited 1.23 V of electrochemical stable window hinders the energy output of aqueous supercapacitors. Good stability of current collectors toward high operation voltage closely determines whether the voltage window of aqueous supercapacitors can be further improved. Here, the electrochemical stability of representative current collectors in aqueous electrolytes in terms of intrinsic response toward oxygen/hydrogen evolution side reaction and capacitance contribution are decoupled detailedly. The lowest response to the occurrence of electrolyte decomposition and negligible capacitance contribution are presented for Ti mesh, along with a high & stable electrochemical window up to 3.61 V in neutral electrolyte and accurate evaluation of the electrochemical performance of electrode. The experimental verification in 21 m LiTFSI confirms that the Ti mesh can indeed work at a record high voltage up to 2.6 V. Operando Raman, ex situ atomic force microscopy, X‐ray photoelectron spectroscopy, and self‐built electrolyte decoupling system further reveal the process of Ni leaching and generation of Ni(OH)2 new species in promising neutral electrolyte for commonly used Ni foam current collector. This work supplies theoretical support for the choice of current collectors in high‐voltage aqueous supercapacitors and the design of catalysts, and intrinsic activity decoupling in the electrocatalytic conversion of small molecules related to aqueous electrolytes.
4‐(Dimethylamino)Pyridinium Azide in Protic Ionic Liquid Media as a Stable Equivalent of Hydrazoic Acid
Authors: Andreev Ivan A. , Boichenko Maksim A. , Ratmanova Nina K. , Ivanova Olga A. , Levina Irina I. , Khrustalev Victor N. , Sedov Igor A. , Trushkov Igor V.
Published: June 2022

We report a procedure for the multigram synthesis of 4‐(dimethylamino)pyridinium azide, a stable, non‐explosive, low‐hygroscopic source of azide ion soluble in both protic and aprotic organic solvents. In protic ionic liquid media this reagent was shown to serve as a safer equivalent of toxic and unstable hydrazoic acid. The synthetic utility of this system was demonstrated using donor‐acceptor cyclopropane ring opening as a model process. General procedures furnishing a variety of dialkyl (2‐azido‐2‐arylethyl)malonates or 4‐azido‐4‐arylbutyrates, depending on the protic ionic liquid applied, were elaborated. The conversion times for studied donor‐acceptor cyclopropanes were established providing the relative reactivity sequence. The application of 4‐(dimethylamino)pyridinium azide for a conventional nucleophilic substitution, oxirane ring opening, (3+2)‐cycloaddition to (thio)cyano group as well as their combinations realized as telescopic synthesis was also demonstrated.

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Enhancers of Host Immune Tolerance to Bacterial Infection Discovered Using Linked Computational and Experimental Approaches
Authors: Sperry Megan M. , Novak Richard , Keshari Vishal , Dinis Alexandre L. M. , Cartwright Mark J. , Camacho Diogo M. , Paré Jean‐François , Super Michael , Levin Michael , Ingber Donald E.
Published: June 2022

Current therapeutic strategies against bacterial infections focus on reduction of pathogen load using antibiotics; however, stimulation of host tolerance to infection in the presence of pathogens might offer an alternative approach. Computational transcriptomics and Xenopus laevis embryos are used to discover infection response pathways, identify potential tolerance inducer drugs, and validate their ability to induce broad tolerance. Xenopus exhibits natural tolerance to Acinetobacter baumanii, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae bacteria, whereas Aeromonas hydrophila and Pseudomonas aeruginosa produce lethal infections. Transcriptional profiling leads to definition of a 20‐gene signature that discriminates between tolerant and susceptible states, as well as identification of a more active tolerance response to gram negative compared to gram positive bacteria. Gene pathways associated with active tolerance in Xenopus, including some involved in metal ion binding and hypoxia, are found to be conserved across species, including mammals, and administration of a metal chelator (deferoxamine) or a HIF‐1α agonist (1,4‐DPCA) in embryos infected with lethal A. hydrophila increased survival despite high pathogen load. These data demonstrate the value of combining the Xenopus embryo infection model with computational multiomics analyses for mechanistic discovery and drug repurposing to induce host tolerance to bacterial infections.
Uncovering haplotype diversity in cultivated Mexican vanilla species
Authors: Ellestad Paige , Farrera Miguel Angel Perez , Forest Félix , Buerki Sven
Published: June 2022

Premise

Although vanilla is one of the best‐known spices, there is only a limited understanding of its biology and genetics within Mexico, where its cultivation originated and where phenotypic variability is high. This study aims to augment our understanding of vanilla's genetic resources by assessing species delimitation and genetic, geographic, and climatic variability within Mexican cultivated vanilla.

Methods

Using nuclear and plastid DNA sequence data from 58 Mexican samples collected from three regions and 133 ex situ accessions, we assessed species monophyly using phylogenetic analyses and genetic distances. Intraspecific genetic variation was summarized through the identification of haplotypes. Within the primarily cultivated species, Vanilla planifolia, haplotype relationships were further verified using plastome and rRNA gene sequences. Climatic niche and haplotype composition were assessed across the landscape.

Results

Three species (Vanilla planifolia, V. pompona, and V. insignis) and 13 haplotypes were identified among Mexican vanilla. Within V. planifolia haplotypes, hard phylogenetic incongruences between plastid and nuclear sequences suggest past hybridization events. Eight haplotypes consisted exclusively of Mexican samples. The dominant V. planifolia haplotype occurred throughout all three regions as well as outside of its country of origin. Haplotype richness was found to be highest in regions around Papantla and Chinantla.

Conclusions

Long histories of regional cultivation support the consideration of endemic haplotypes as landraces shaped by adaptation to local conditions and/or hybridization. Results may aid further genomic investigations of vanilla's genetic resources and ultimately support the preservation of genetic diversity within the economically important crop.
On the choice of timescale for other cause mortality in a competing risk setting using flexible parametric survival models
Authors: Skourlis Nikolaos , Crowther Michael J. , Andersson Therese M.‐L. , Lambert Paul C.
Published: June 2022

In competing risks settings where the events are death due to cancer and death due to other causes, it is common practice to use time since diagnosis as the timescale for all competing events. However, attained age has been proposed as a more natural choice of timescale for modeling other cause mortality. We examine the choice of using time since diagnosis versus attained age as the timescale when modeling other cause mortality, assuming that the hazard rate is a function of attained age, and how this choice can influence the cumulative incidence functions (s) derived using flexible parametric survival models. An initial analysis on the colon cancer data from the population‐based Swedish Cancer Register indicates such an influence. A simulation study is conducted in order to assess the impact of the choice of timescale for other cause mortality on the bias of the estimated and how different factors may influence the bias. We also use regression standardization methods in order to obtain marginal estimates. Using time since diagnosis as the timescale for all competing events leads to a low degree of bias in for cancer mortality () under all approaches. It also leads to a low degree of bias in for other cause mortality (), provided that the effect of age at diagnosis is included in the model with sufficient flexibility, with higher bias under scenarios where a covariate has a time‐varying effect on the hazard rate for other cause mortality on the attained age scale.
Synthesis and biological evaluation of anilide derivatives as epidermal growth factor receptor L858R/T790M and L858R/T790M/C797S inhibitors
Authors: Kim Soo Lim , Yang Yo‐Sep , Lee Sujin , Kim Nam‐Jung
Published: June 2022

Development of a mutant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor is important for the treatment of various cancers. Third‐generation EGFR tyrosine kinase inhibitors (TKIs) have been clinically used by targeting T790M specifically but are recently known to induce T790M/C797S mutation after the treatment. Therefore, there is an unmet need to develop novel kinase inhibitors targeting the mutant EGFRs. Here, we designed and synthesized 16 analogs by hybridizing EAI045 (1) and 3′,4′,5′‐trihydroxyflavone (2) and identified 9a, 9b, and 20b as EGFR L858R/T790M/C797S mutant inhibitors. In addition, we found that 10a and 10b can inhibit both L858R/T790M and L858R/T790M/C797S. Molecular docking study on a plausible binding mode of the compounds is also provided.
In‐depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS‐331007 and ledipasvir in rat plasma using LC–MS
Authors: Aboras Sara I. , Korany Mohamed A. , El‐Yazbi Ahmed F. , Ragab Marwa A. A. , Abdine Heba H.
Published: June 2022

The use of complementary medicine (CMD) for liver support in Hepatitis C virus (HCV) patients sometimes coincides with the administration of oral antiviral drugs to eradicate the virus. This calls for a deep investigation of CMD effects on the pharmacokinetic parameters of these drugs to ensure their safety and efficacy. Silymarin (SLY), as a CMD, was selected to be given orally to healthy male rats with sofosbuvir (SFB) and ledipasvir (LED), a common regimen in HCV treatment. A new and sensitive LC–MS method was validated for the bioassay of SLY, LED, SFB and its inactive metabolite, GS‐331007, in spiked plasma with lower limits of quantitation of 10, 1, 4 and 10 ng/ml, respectively. Moreover, the method was further applied to conduct a full pharmacokinetic profile of SFB, GS‐331007 and ledipasvir with and without SLY. It was found that co‐administration of SLY may expose the patient to unplanned high serum concentrations of SFB and LED. This could be accompanied by a decrease in SFB efficacy, potentially leading to therapeutic failure and the emergence of viral resistance.
Experimental Investigation of Electrothermal Desorption of Steel Mill Gases from Activated Carbon
Authors: Peters Martin , Geitner Christian , Verhoeven Birte Friederike
Published: June 2022

A bench‐scale electric swing adsorption plant has been used to investigate electrothermal desorption behavior by varying technically relevant factors like maximum electric power, purge gas flow and desorption temperature. The study has been planned by design of experiments using a central composite design. Different quality criteria have been defined to describe a macroscopic behavior of the desorption for process development. The results are used to fit models by multiple linear regression. For technically relevant quality criteria good correlating models could be found and can be used for accurate prediction of, e.g., the energy demand, purge gas total volume or desorption time.