bluuebunny/crossref_metadata_2025 huggingface dataset:
ESKİ MEZOPOTAMYA’DA DOMUZ, DOMUZ YETİŞTİRİCİLİĞİ VE DOMUZUN RİTÜEL METİNLERİNDE KULLANIMIYLA İLGİLİ ÇEŞİTLİ KAYITLAR
Authors: ÖZ KİRİŞ Esma
Published: March 2023

Mezopotamya’da domuz, daha çok eti ve yağı için yetiştirilen bir hayvandı. Kısa zaman içerisinde çok yavru yapabilen domuzlar önemli bir et kaynağıydı. Domuz, Eski Mezopotamya kaynaklarında özellikle III.Ur/Yeni Sumer dönemine tarihlenen Ur, Garšana, Umma, Lagaš, Puzriš Dagan gibi önemli kentlerde ele geçen ekonomik içerikli arşivlerde ve Eski Babil döneminden bazı kaynaklarda sıklıkla geçmektedir. Domuzlar, uzak mesafe yolculukları için uygun hayvanlar olmadığından, yeniden dağıtımı yapılamadığından ve aynı zamanda süt ve yumurta gibi temel ürün sağlayan bir hayvan olmaması sebebiyle domuz yetiştiriciliğinin yerel yönetim tarafından pek desteklenmediği görüşü yaygındır. Domuz yetiştiriciliğinin, genellikle küçük ölçekte, daha mütevazi çiftçi ailelerin uğraştığı bir faaliyet olduğu düşünülmektedir. Domuz yetiştiriciliği konusunda en zengin bilgiler III.Ur dönemine ait Lagaš arşivinden ve Eski Babil dönemi kayıtlarından gelmektedir. Mezopotamya’da düzenlenen festivallerde, bayramlarda ve cenaze törenlerinde katılımcılara sunmak amacıyla çeşitli kasabalardan büyükbaş ve küçükbaşlarla birlikte domuzların da sipariş verilen hayvanlar arasında olduğu çivi yazılı belgelerde kayıtlıdır. Domuzlar, sadece eti ve yağı için tüketilmiyordu. Aynı zamanda kötülüğü/büyüyü kovma/bozma ritüellerinde, olumsuzluğun yüklendiği nesne olarak yani “yerini alma” ritüellerinde de kullanılan bir hayvandı. Çivi yazılı belgelerle birlikte, başta silindir mühürler olmak üzere rölyeflerde, muskalarda, kil figürlerde ve çeşitli arkeolojik eserlerin üzerinde domuz betimlemelerini görmek mümkündür. Bu çalışmamızın sınırları, ağırlıklı olarak domuzlarla ilgili bilgilerin en sık kaydedildiği III.Ur dönemi metinleri ve Eski Babil döneminden bazı belgeler çerçevesinde şekillenmiştir. Domuzların ritüellerde kullanımına ilişkin birtakım metinler de bu çalışmada ele alınmıştır.
KRİZLER VE İSYANLAR: ROMA’NIN ARMENİA POLİTİKASI (MÖ 74-66)
Authors: DOĞANCI Kamil , TOSUN Serhat Pir
Published: March 2023

Pergamon Krallığı’nın vasiyet yoluyla Roma’ya bırakılması ve Roma’nın da MÖ 129 yılında Pergamon Krallığı’na ait topraklarda Provincia Asia’yı kurması Anadolu’yu büyük bir krize sürüklemiştir. Bu süreçte, Roma’nın Anadolu’daki varlığından rahatsızlık duyan, Pergamon Hanedanı’ndan olduğunu iddia eden Aristonikos ve Pontos Kralı VI. Mithridates Roma’ya karşı direnmişlerdir. Aristonikos İsyanı, kısa süre içinde bastırılsa da VI. Mithridates’in yarattığı kriz ortamı Roma-Pontos Savaşı’nın Armenia’ya kadar sıçramasına neden olmuştur. VI. Mithridates ve müttefikleri Parth İmparatoru II. Mithridates ve Armenia kralı olan damadı II. Tigranes, Kappadokia Kralı I. Ariobarzanes’i defalarca tahttan indirerek Roma’nın tepkisini çekmiş ve nihayetinde Roma ve VI. Mithridates karşı karşıya gelmiştir. Roma, Parth İmparatorluğu’nun da bu güç dengesinde rolü olduğunu öğrenince MÖ 96/95 yılında Sulla önderliğinde Parthlarla saldırmazlık antlaşması yapmıştır. Mithridates Savaşları’nda ise Roma, MÖ 72 yılındaki Kyzikos kuşatmasının ardından psikolojik üstünlüğü ele geçirmiş, VI. Mithridates ise Armenia’ya sığınmak zorunda kalmıştır. Onu takip eden Lucullus komutasındaki Roma ordusu Armenia'ya saldırmış ve MÖ 69 yılında Tigranokerta Savaşı’nda II. Tigranes’i mağlup ederek Armenia topraklarını ele geçirme şansını yakalamıştır. Senatus’un onayını almadan Armenia’ya saldırması ve publicani ile yaşadığı sorunlar nedeniyle Lucullus görevinden alınmış ve yerine Gn. Pompeius Magnus atanmıştır. Pompeius’un bölgeye gelmesiyle birlikte Roma’nın Armenia’daki siyasi düzeni kendi çıkarlarına göre düzenlemeye başladığı görülmektedir. II. Tigranes ve oğlu Genç Tigranes arasındaki anlaşmazlıklardan yararlanan Pompeius, MÖ 66 yılında Artaxata Antlaşması ile birlikte Armenia ve Sophene krallığını paylaştırmıştır. Bu süreçte Roma’nın bölgedeki dengeleri göz önünde tutarak çıkarları doğrultusunda esnek bir politika izlediği görülmektedir.
ELAIUSSA SEBASTE’DEN PHOKAIA KIRMIZI ASTARLI SERAMİKLERİN ÖN DEĞERLENDİRMESİ
Authors: KIZILARSLANOĞLU Asena , AKTAŞ Rabia
Published: March 2023

Dağlık Kilikia Bölgesi’nin en önemli liman kentlerinden biri olan Elaiussa Sebaste, Akdeniz ticari sisteminde aktif bir geçiş ve durak noktası olmuştur. Kazılar sonucu tespit edilen veriler, Roma ve Geç Roma-Erken Bizans Dönemleri’nde tüm Akdeniz coğrafyasında dolaşımda olan pek çok amphora, mutfak kapları ve Kırmızı Astarlı Seramikler’den oluşan geniş bir form dizisi ile kentin ticaret merkezi olgusunu desteklemektedir. Kentin MS 4. yüzyıldan itibaren yerel üretimi olan LR1 amphoralarını dış piyasaya ulaştırabilme avantajı, uzak bölgelerden farklı ürün gruplarını temin edebilmesini kolaylaştırmıştır. Bu grupların en başında ise Kırmızı Astarlı Seramikler gelmektedir. Geç Roma–Erken Bizans Dönemleri’nde geniş bir coğrafi alanda, değişik formlarda üretilen ve yayılan bu gruba ait seramikler, bölgelerin ekonomik düzeyi ve ticaret sisteminin değerlendirilmesini kolaylaştırmakta ve ticari rotaların belirlenmesini sağlamaktadır. Elaiussa Sebaste’de ele geçen, Akdeniz ticaret sistemi içerisinde yer alan farklı seramik gruplarının yayınlanması, kentin üretim, ithalat ve ihracat dinamiği konusunda daha net bilgiler verecektir. Makalenin konusunu oluşturan Phokaia üretimi kaliteli servis kapları da Geç Antik Çağ’da var olan yoğun ticari faaliyetlerin göstergesi olarak Kilikia ve Ege Bölgesi arasındaki ticari ilişkilere, Sebaste özelinde yeni bir kanıt oluşturmaktadır. Bu bağlamda, Sebaste’de yoğun olarak kullanıldığı anlaşılan Phokaia Kırmızı Astarlı Seramikleri’nin form gruplarının saptanması ve tipolojik özelliklerinin sunulmasının yanı sıra, Elaiussa Sebaste’nin özellikle Phokaia ile ticari ilişkilerine ait veriler sunulmuştur.
A Tale of Two Fjords
Authors:   , Stuart-Lee Alice Elizabeth
Published: March 2023

Glaciers exert a strong influence on the hydrography and biogeochemistry of arctic fjord environments through the export of large quantities of particles, freshwater and ice. In turn, they contribute to the shaping of the marine ecosystems upon which local communities are heavily reliant. Extensive glacial changes are occurring along the coasts of Greenland, and their effects on the surrounding fjord environments are becoming increasingly visible. Motivated by the question of what we can expect in terms of future fjord transformations under continued glacial retreat, this thesis examines seasonal patterns in two neighbouring fjords on the southwest coast of Greenland: Nuup Kangerlua (Godthåbsfjord), a predominately marine-terminating system, and Ameralik, which receives glacial meltwater only from a land-terminating glacier. Seasonal differences in hydrography, biogeochemistry and ecology are described, with an emphasis on the role of glaciers in these processes.
‘But not that which has lost its soul is what is potentially alive’ – The Relation between Body and Soul in Aristotle
Authors: Buchheim Thomas
Published: March 2023

The thus far little noticed element in Aristotle's definition of the soul – namely, its nexus to the particularities of a complex physical body (σῶμα φυσικόν / sôma physikon) – is the key to resolve three apparent inconsistencies of Aristotelian hylomorphism: First, the incompatible modalities of the assumed binding relation between physical body as a simultaneously functional matter and the soul as its form; second, the homonymy problem, i.e., that, according to Aristotle's own statement, a body’s remnant that was abandoned by its soul can only homonymously be called that which it was when it was alive; third, the problem that form in hylomorphism seems to be nothing but a configuration of material parts, which, though conceptualised in abstraction and independent from matter, would nevertheless add nothing new to the material composition in which it is instantiated. If that were so, how, then, can a hylomorphic theory conceive of form as ontologically separate from matter? Without a comprehensive and comprehensible resolution of those three major aporias – that is in line with today’s scientific conception of the world – Aristotle’s definition of the soul as form-without-matter would, in Ackrill's words, ‘resist interpretation’. This paper shows that such a resolution can in fact be achieved and that Aristotle’s hylomorphism allows for a plausible and consistent interpretation.
Evaluation of Seedling Resistance and Marker Assisted Selection for Leaf Rust (Puccinia triticina) Resistance in Pakistani Wheat Landraces, Cultivars and Advanced Lines
Authors: Channa Abdul W. , Bux Hadi , Jatoi Ghulam H. , Sial Mahboob A. , Shah Syed M. A. , Figari Isabel M. G. , Koondhar Naimatullah
Published: March 2023

Leaf rust is amongst major biotic constraints of wheat (Triticum aestivum L.) having ability to cause substantial yield reductions worldwide. A continuous exploration for novel sources of resistance is pre-requisite for its management. Objectives of study were to conduct resistance evaluation of 112 Pakistani landraces and 48 advanced lines/ cultivars at seedling stage with total 10 virulent pathotypes of leaf rust, 3 from Pakistan and 7 from U.S.A and to detect closely linked markers for Lr10, 16, 34 and 67 genes through marker-assisted selection (MAS). Findings revealed most of Pakistani landraces showed lack of resistance at seedling stage. Only 7 accessions of landraces and 11 advanced lines were found highly resistant against all pathotypes of Pakistan. Similarly, 10 advanced lines exhibited high resistance while variability in resistance was recorded for landraces against all pathotypes tested from USA. Marker-assisted selection revealed Lr genes i.e. Lr10, Lr16, Lr34 and Lr67 were present at various frequencies. Highest frequency was observed for Lr34 followed by Lr16 Lr67 while lowest was recorded for Lr10. These genetic resources and lines identified effective against Pakistan and USA pathotypes are potential sources for improvement of leaf rust (LR) resistance and can be utilized as valuable material for breeding resistant wheat cultivars.
Pathogenic Characterization of Three Fusarium Species Associated with Onion (Allium cepa L.) In Burkina Faso
Authors: Hamidou Sogoba K. , Kadidia Koita , Alassane Ouattara , Mohamed Sana , Itolou Kassankogno A. , Harouna Sawadogo , Claudine Campa
Published: March 2023

Basal rot is a widespread onion disease caused by fungi belonging to Fusarium genus. The disease is known to incur onion yield loss worldwide. This study aims to identify and determine the pathogenicity of Fusarium species associated with basal rot of onions in Burkina Faso. Thirteen Fusarium isolates from seven regions of Burkina Faso were identified based on morphological observations and molecular diagnosis and their pathogenicity was assessed in laboratory and Greenhouse. Results showed that, the 13 isolates belonged to Fusarium falciforme, Fusarium acutatum and Fusarium oxysporum species. F. falciforme, F. acutatum and F. oxysporum were pathogenic on onion seeds, seedlings and bulbs. F. falciforme caused lower seedling damping-off rate compared to that caused by F. acutatum and F. oxysporum. All these species of Fusarium genus induced onion bulbs rots. The results of this study confirmed the presence of these species in Burkina Faso and that they are pathogenic on onion. Therefore, it would be useful to suggest an implement sustainable management approach of these pathogens.
The corroletion between nurse work stress and nurse performance during the covid-19 pandemic
Authors: Widyayantiningsih Sri , Suci Lukyta , Feriani Nita , Muklis Muatul , Dwi Yeti , Susandiatman Anis
Published: March 2023

Various psychological disorders have been reported and published during the Covid-19 outbreak, one of which is stress. Nurse stress can interfere with nurse performance if it is not quickly resolved. The purpose of this study was to analyze the relationship between nurse work stress and nurse performance during the Covid-19 pandemic. This research is an analytic observational study with a cross sectional approach. The population in this study were 46 nurses in the inpatient room of Mas Mansur Building and the Emergency Room of RSU Aminah Blitar. The entire population is used as a sample, namely as many as 46 nurses. Nurse work stress was measured using a questionnaire from DASS-21 and nurse performance was measured using a questionnaire that had been prepared by the researcher.ρ = 0.000). It was concluded that the higher the work stress felt by the nurse, the lower the nurse's performance
Integration of hydrogels in microfabrication processes for bioelectronic medicine: Progress and outlook
Authors: Saghir Saloua , Imenes Kristin , Schiavone Giuseppe
Published: March 2023

Recent research aiming at the development of electroceuticals for the treatment of medical conditions such as degenerative diseases, cardiac arrhythmia and chronic pain, has given rise to microfabricated implanted bioelectronic devices capable of interacting with host biological tissues in synergistic modalities. Owing to their multimodal affinity to biological tissues, hydrogels have emerged as promising interface materials for bioelectronic devices. Here, we review the state-of-the-art and forefront in the techniques used by research groups for the integration of hydrogels into the microfabrication processes of bioelectronic devices, and present the manufacturability challenges to unlock their further clinical deployment.
Political, economic, and governance attitudes of blockchain users
Authors: Korpas Lucia M. , Frey Seth , Tan Joshua
Published: March 2023

We present a survey to evaluate crypto-political, crypto-economic, and crypto-governance sentiment in people who are part of a blockchain ecosystem. Based on 3,710 survey responses, we describe their beliefs, attitudes, and modes of participation in crypto and investigate how self-reported political affiliation and blockchain ecosystem affiliation are associated with these. We observed polarization in questions on perceptions of the distribution of economic power, personal attitudes towards crypto, normative beliefs about the distribution of power in governance, and external regulation of blockchain technologies. Differences in political self-identification correlated with opinions on economic fairness, gender equity, decision-making power and how to obtain favorable regulation, while blockchain affiliation correlated with opinions on governance and regulation of crypto and respondents’ semantic conception of crypto and personal goals for their involvement. We also find that a theory-driven constructed political axis is supported by the data and investigate the possibility of other groupings of respondents or beliefs arising from the data.
Targeting dormant phenotype acquired mycobacteria using natural products by exploring its important targets: In vitro and in silico studies
Authors: Sharma Shweta , Chikhale Rupesh , Shinde Nivedita , Khan A. M. , Gupta Vivek Kumar
Published: March 2023

The dormant phenotype of Mycobacterium tuberculosis that develops during infection poses a major challenge in disease treatment, since these bacilli show tolerance to front-line drugs. An in vitro hypoxia dormancy model was established, which produced phenotypically dormant Mycobacterium smegmatis after prolonged incubation under conditions of low oxygen, low pH, and nutrient limitation. Bacilli in this model displayed the classical dormancy characters, including loss of acid fastness, altered morphology, and, most importantly, tolerance to front-line drugs. The dormant form of M. smegmatis was treated with drugs and phytomolecules. Three phytomolecules exhibited activity against dormant bacilli, as shown by lack of regrowth in solid and liquid media. Further investigation of dormancy-active hits was carried out using in silico approaches to understand the druggable targets of these phytomolecules in dormant bacilli. For this study, molecular docking, molecular dynamics simulations (MDS), and molecular mechanics-generalized born solvent accessibility (MM-GBSA)-based binding energy (ΔGbind) calculations were performed. Five different targets, namely, isocitrate lyase (ICL), GMP synthase, LuxR, DosR, and serine/threonine protein kinase (STPK), from M. smegmatis and M. tuberculosis were studied in details. DosR and STPK were found to be the common targets in both the species that were more prone to the phytomolecules. The standard DosR inhibitor, HC104A, showed a lower dock score and binding energy of −4.27 and −34.50 kcal/mol, respectively, compared to the natural products under study. The phytomolecule, icariin, showed better docking score (dock score = −5.92 kcal/mol with and binding energy ΔGbind= −52.96 kcal/mol) with DosR compared to known DosR inhibitor, HC104A (dock score = −4.27 kcal/mol and binding energy ΔGbind = −34.50 kcal/mol). Similarly, the known STPK inhibitor MRCT67127 showed a lower dock score and binding energy of −4.25 and −29.43 kcal/mol, respectively, compared to the phytomolecule, icariin (dock score = −5.74 kcal/mol and ΔGbind= −43.41 kcal/mol). These compounds might ultimately lead to new therapeutics or may be useful as adjuvants to the first-line drugs to reduce the lengthy anti-TB therapy in the future.
Trapped or staying put: Governing immobility in the context of climate change
Authors: Thornton Fanny , Serraglio Diogo Andreolla , Thornton Alec
Published: March 2023

By presenting a range of outcomes which result from the impacts of a changing environment on human mobility patterns, the Foresight Report on Migration and Global Environmental Change emphasized that, whereas some people choose to stay in a specific location, others are simply unable to leave, leading to what the report termed “trapped populations”. Much understanding about both voluntary and involuntary immobility in the context of environmental or climatic change has been gained since. The IPCC's recent report on climate change impacts, vulnerabilities and adaptation further underlined that, in the decades ahead, some people will be unable or unwilling to move away from locations in which they may nevertheless be vulnerable to the impacts of climate change. What has received less attention is how climate immobility ought to be governed and which norms should underpin its governance. In this paper, we rely on select existing law and policy instruments and frameworks from Latin American and the Pacific Islands regions to outline key considerations of a governance structure suitable for (in)voluntary immobility. This will inform individuals, communities, and policy makers who seek to navigate through complex reasons and decisions for “staying put” or “getting stuck” in the face of climatic change. The analysis builds upon a review of published literature and, especially, existing policy and legal frameworks at national and regional levels. We argue that a more widespread, timely and proactive approach to policy and governance is required in support of resilience in the context of climate immobility.
Experimental study of distribution and quantitative characterization of discontinuous oil phase based on micro-CT
Authors: Yang Jiangshan , Shan Gaojun , Wang Zhiqiang , Zhang Qi , Yang Yongfei , Ma Wenjie
Published: March 2023

When a sandstone reservoir enters the ultra-high water cut stage, the oil phase changes from continuous to discontinuous, which results in difficulties in the further development and utilization of the reservoir. It is important to clarify the flow law and distribution state of discontinuous oil phases to guide the remaining oil production. This study selected samples from sandstone reservoirs, accurately obtained oil and water phase information from digital core, and constructed matrix based on three-dimensional CT scanning to study the law of discontinuous oil phase distribution. We used digital cores to construct pore network models and calculate the pore radius, throat radius, pore-throat ratio, coordination number, and tortuosity to study the influence of pore structure on discontinuous oil phase flow law. A micro-displacement experiment consisting of two phases of simulated reservoir and development was designed. To improve the accuracy of the experiment, the related pressure was controlled to form bound water in the simulated reservoir formation stage. In the simulated reservoir development phase, in situ scanning of cores at different displacement stages was performed to obtain oil and water distributions at different stages in the same location. The number of oil droplets, 3D shape factor, Euler number, and saturation coefficient of the oil phase were calculated, and the micro-remaining oil clumps were quantitatively analyzed. According to the morphology and distribution characteristics, the remaining oil of the discontinuous phase was divided into the types of the throat, film, droplet, island, and corner. The results showed that the sample with a small pore-throat ratio, large coordination number, and small tortuosity was more likely to form dominant channels; moreover, the remaining oil was more concentrated in this state. In the remaining oil of the discontinuous phase, the number of droplets was the largest and had an obvious displacement effect. The island number was small because the selected samples had good connectivity and it is difficult to form large oil droplets in a single pore. In the ultra-high water cut stage, the throat number increased slowly, which was related to the formation of dominant channels. The corner and the film were difficult to displace; thus, their numbers increased steadily. The quantitative characterization of the discontinuous oil phase is helpful for further study of remaining oil at the pore scale.
Type 1 diabetes in low and middle-income countries - Tanzania a streak of hope
Authors: Ludvigsson Johnny , Edna Majaliwa , Ramaiya Kaushik
Published: March 2023

Introduction

In several of the Low and Middle Income countries , many patients with Type 1 diabetes (T1D) are most probably not diagnosed at all which may contribute to their low incidence. As an example of a country with low income and poor resources, we have chosen to study T1D in children/young people in Tanzania.

Methods

Analyses of casebooks and statistics at several Tanzanian hospitals treating young patients with insulin dependent diabetes, usually Type 1 diabetes, and collection of information from different organisations such a Tanzanian Diabetes Association, Life for a Child, Changing Diabetes in Children and World Diabetes Foundation.

Results

The incidence in several areas is low. However, a lot of data are often missing at studied clinics and therefore the incidence might be higher, and with increased awareness in recent years the number of patients has increased many-folds. Most patients present with typical symptoms and signs of T1D, and a high proportion with plausible ketoacidosis , although this proportion has decreased from about 90% to about 40% in recent decades. Many patients have poor blood glucose control, and complications often develop already after short diabetes duration. In recent years resources have increased, awareness has increased and diabetes clinics started where staff has got training.

Conclusions

There are problems with diabetes care in Tanzania but several facts give hope for the future.
A comprehensive validation study of the latest version of BoneXpert on a large cohort of Caucasian children and adolescents
Authors: Maratova Klara , Zemkova Dana , Sedlak Petr , Pavlikova Marketa , Amaratunga Shenali Anne , Krasnicanova Hana , Soucek Ondrej , Sumnik Zdenek
Published: March 2023

Introduction

Automated bone age assessment has recently become increasingly popular. The aim of this study was to assess the agreement between automated and manual evaluation of bone age using the method according to Tanner-Whitehouse (TW3) and Greulich-Pyle (GP).

Methods

We evaluated 1285 bone age scans from 1202 children (657 scans from 612 boys) by using both manual and automated (TW3 as well as GP) bone age assessment. BoneXpert software versions 2.4.5.1. (BX2) and 3.2.1. (BX3) (Visiana, Holte, Denmark) were compared with manual evaluation using root mean squared error (RMSE) analysis.

Results

RMSE for BX2 was 0.57 and 0.55 years in boys and 0.72 and 0.59 years in girls, respectively for TW3 and GP. For BX3, RMSE was 0.51 and 0.68 years in boys and 0.49 and 0.52 years in girls, respectively for TW3 and GP. Sex- and age-specific analysis for BX2 identified the largest differences between manual and automated TW3 evaluation in girls between 6-7, 12-13, 13-14 and 14-15 years, with RMSE 0.88, 0.81, 0.92 and 0.84 years, respectively. The BX3 version showed better agreement with manual TW3 evaluation (RMSE 0.64, 0.45, 0.46 and 0.57).

Conclusion

The latest version of the BoneXpert software provides improved and clinically sufficient agreement with manual bone age evaluation in children of both sexes compared to the previous version and may be used for routine bone age evaluation in non-selected cases in pediatric endocrinology care.
What endocrinologists can do to prevent cardiovascular complications in adults with Prader-Willi syndrome: Lessons from a case series
Authors: Pellikaan Karlijn , van Weijen Paula M. H. , Rosenberg Anna G. W. , Hoekstra Franciska M. E. , Vermaak Michiel , Oomen Peter H. N. , van der Lely Aart J. , Cuypers Judith A. A. E. , de Graaff Laura C. G.
Published: March 2023

Context

Prader-Willi syndrome (PWS) is a complex rare genetic syndrome. Mortality in patients with PWS is 3% per year. In nearly half of the patients, the cause of death is of cardiopulmonary origin. Prevention, diagnosis and treatment of cardiovascular (CV) disease in PWS adults is complicated by the behavioral phenotype, reduced ability to express physical complaints, high pain threshold and obesity.

Objective

To describe the challenges in prevention, diagnosis and treatment of CV disease in PWS adults, in order to increase awareness and improve medical care.

Methods

Retrospective study of medical records of adults visiting the Dutch PWS reference center.

Results

We describe the challenges encountered during diagnosis and treatment of four PWS adults with heart failure. All had pre-existent peripheral edema. CV risk factors in these patients were obesity (n=4), type 2 diabetes mellitus (n=2), hypertension (n=2), hypogonadism (n=3) and sleep apnea (n=2). Remarkably, all patients were younger than 40 years during their first cardiac decompensation. All patients presented with progressive shortness of breath and/or orthopnea and progressive pitting edema. In 117 controls with PWS without CV problems, 31% had leg edema.

Conclusion

Diagnosing CV problems in PWS adults is challenging. Peripheral edema is common in PWS adults without CV morbidity, which makes edema in general a poor marker for heart failure. However, when edema is of the pitting kind and progressive, this is a strong predictor of cardiac decompensation. We provide practical recommendations for diagnosing and treating CV problems in this vulnerable patient population.
Metabolic syndrome-related prognostic index: Predicting biochemical recurrence and differentiating between cold and hot tumors in prostate cancer
Authors: Ren Congzhe , Wang Qihua , Wang Shangren , Zhou Hang , Xu Mingming , Li Hu , Li Yuezheng , Chen Xiangyu , Liu Xiaoqiang
Published: March 2023

Background

The prostate, as an endocrine and reproductive organ, undergoes complex hormonal and metabolic changes. Recent studies have shown a potential relationship between metabolic syndrome and the progression and recurrence of prostate cancer (PCa). This study aimed to construct a metabolic syndrome-related prognostic index (MSRPI) to predict biochemical recurrence-free survival (BFS) in patients with PCa and to identify cold and hot tumors to improve individualized treatment for patients with PCa.

Methods

The Cancer Genome Atlas database provided training and test data, and the Gene Expression Omnibus database provided validation data. We extracted prognostic differentially expressed metabolic syndrome-related genes (DEMSRGs) related to BFS using univariate Cox analysis and identified potential tumor subtypes by consensus clustering. The least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression were used to construct the MSRPI. We further validated the predictive power of the MSRPI using KaplanMeier survival analysis and receiver operating characteristic (ROC) curves, both internally and externally. Drug sensitivity was predicted using the half-maximal inhibitory concentration (IC50). Finally, we explored the landscape of somatic mutations in the risk groups.

Results

Forty-six prognostic DEMSRGs and two metabolic syndrome-associated molecular clusters were identified. Cluster 2 was more immunogenic. Seven metabolic syndrome-related genes (CSF3R, TMEM132A, STAB1, VIM, DUOXA1, PILRB, and SLC2A4) were used to construct risk equations. The high-risk index was significantly associated with a poor BFS, which was also validated in the validation cohort. The area under the ROC curve (AUC) for BFS at 1-, 3-, and 5- year in the entire cohort was 0.819, 0.785, and 0.772, respectively, demonstrating the excellent predictive power of the MSRPI. Additionally, the MSRPI was found to be an independent prognostic factor for BFS in PCa. More importantly, MSRPI helped differentiate between cold and hot tumors. Hot tumors were associated with the high-risk group. Multiple drugs demonstrated significantly lower IC50 values in the high-risk group, offering the prospect of precision therapy for patients with PCa.

Conclusion

The MSRPI developed in this study was able to predict biochemical recurrence in patients with PCa and identify cold and hot tumors. MSRPI has the potential to improve personalized precision treatment.
The digital economy and corporate credit risk: An empirical study based on Chinese new energy enterprises
Authors: Su Min , Duan Yu , Cui Yifan
Published: March 2023

The integration of digital technologies is exhibiting an upward trend in Chinese enterprises, and the degree of corporate credit risk is directly proportional to their financial sustainability. Based on panel data of new energy enterprises from 2012 to 2020, this article makes an empirical study on the direct effect, mediating effect, and moderating effect of the digital economy (DE) on the new energy enterprises’ credit risk. It is found that the digital economy could significantly mitigate the credit risk of new energy enterprises by improving total factor productivity and amplifying the potential default cost. When the digital economy affects corporate credit risk, the development of the new energy industry acts as an intermediary, and knowledge spillover acts as a moderator. Furthermore, considering knowledge spillover as the threshold variable, the digital economy has a double-threshold effect. The marginal impact fluctuates from dropping to increasing as the knowledge spillover level increases. As for the region’s heterogeneity, the digital economy has benefited eastern China more than central and western China, possibly due to the differences in economic structure, capital intensity, and policy institutions. In view of these findings, this study provides a reference for China to mitigate corporate credit risk in the digital economy era.
Stimulating effects of submerged plants on removing of N from the water in the Daihai lake of inner Mongolia autonomous region, China
Authors: Yao Yipeng , Jiang Yuhan , Liu Yuhong , Meng Shuang , Hu Bintao , Chen Yixue
Published: March 2023

The Daihai Lake, the third largest lake in Inner Mongolia Autonomous Region, is the cornerstone to maintain the ecosystem balance in this region, which is facing some problems including size shrinking, water quality declining and biodiversity decreasing largely in recent years. In order to quantify the N purification amount of submerged plants, Stella software was used in this study to construct a nitrogen dynamic model to simulate the nitrogen cycle process in the Daihai Lake and the participation of submerged plants in this cycle process. The results showed that based on the submerged plant growth area in 2019 in the Daihai Lake, the N uptake by submerged plants this year was 5.13t, accounting for 4.8% of all exogenous pollution (107.895t), Moreover, our model also predicted that the purification capacity of the restored submerged plants with a large area of 9.91 km2 in the Daihai Lake was significantly higher than before restoration. And the N pollution load of 107.892t in the Daihai Lake could be purified by this stored pattern in 12 years, while during this process a regular cleaning of submerged plant residues was required. Therefore, only large area restoration of submerged plant would benefit for improving water quality.
QSAR model and microscopic mechanism analysis of dye removal by coagulation of aluminum chloride under alkaline conditions
Authors: Zhang Meilan , Qin Shengnan , Tan Yujia , Shen Zhemin
Published: March 2023

Introduction: The inorganic coagulant AlCl3 is used in the traditional coagulation method for the decolorization of industrial dye wastewater. We studied its effectiveness in 41 kinds of dye with different structures, including azo, anthraquinone, arylmethane, and indigo dyes.

Discussion: The optimal conditions for the removal of dye in the AlCl3 coagulation system were alkaline > neutral > acidic conditions. Under alkaline conditions, the hydrolysis colloid of AlCl3 is positively charged and easily combined with negatively charged anionic dyes by electrostatic adsorption. Therefore, the relationships between the dye removal behavior and molecular parameters under alkaline conditions were analyzed.

Methods: Quantitative structure–activity relationship (QSAR) models were built for the color removal rates (Rexp) of 41 dyes and 46 molecular parameters computed by the density functional theory (DFT). Internal validation, external validation, statistical tests, Y-randomization, and applicability domain tests indicated that the optimal models are stable, accurate, reliable, and predictive.

Results: The optimal QSAR model showed that surface area (approx.) (SAA) and molecular weight (MW) are two key molecular parameters. Moreover, electrostatic forces and hydrogen bonding are the predominant adsorption forces in this coagulation process.
Coevolutionary analysis of the Philopteroides Mey, 2004 (Phthiraptera: Ischnocera) parasitizing bulbuls (Passeriformes: Pycnonotidae)
Authors: Ren Mengjiao , Gustafsson Daniel R. , Tian Chunpo , Grossi Alexandra A. , Liu Zhixiao , Zou Fasheng
Published: March 2023

Introduction

Avian head lice comprise a diverse group of distantly related genera of lice that exhibit a strongly convergent morphology. Due to their lack of free-living stages, their strong morphological adaptations to living on the host’s head, and the limited opportunities for transfer between hosts during mating or nesting, the lateral transmission of head lice between non-conspecific hosts may be presumed to be restricted. Despite this, many species of head lice are ostensibly host generalists. We here examine lice of the head louse genus Philopteroides Mey, 2004, from bulbuls (Passeriformes: Pycnonotidae).

Methods

We use two different methods, ParaFit and Jane, to get insights on the co-evolutionary history of Philopteroides species and their bulbul hosts. Jane was run with a variation of event costs.

Results

Our phylogenetic analysis indicate that several morphologically cryptic species can be found in this group, most of which appear to be host specific. However, co-phylogenetic analyses indicate that host-switching has been common in the history of these lice, and co-speciation events have been rarer than expected. Moreover, lowest-cost co-evolutionary reconstructions under a variety of event costs are indistinguishable from random. An expanded dataset with more Philopterus-complex lice was found to be evenly balanced between host-switching and co-speciation events.

Discussion

The transfer of avian head lice between host species is poorly understood, but evidently fairly common. Several potential routes are discussed, but direct evidence is missing. Potentially, the presence of multiple bulbul species at fruiting trees may be an important factor in this transfer. However, such transfer routes also do not explain why Philopteroides lice on bulbuls appear to be distinct from those of other hosts. Moreover, as many of the species recovered in our analysis are morphologically indistinguishable, cryptic speciation appears to be common in this group.
Floral and genetic divergence across environmental gradients is moderated by inter-population gene flow in Platanthera dilatata (Orchidaceae)
Authors: Wallace Lisa E. , Bowles Marlin L.
Published: March 2023

Understanding how natural selection acts on intraspecific variation to bring about phenotypic divergence is critical to understanding processes of evolutionary diversification. The orchid family is well known for pollinator-mediated selection of floral phenotypes operating among species and along environmental or geographic gradients. Its effectiveness at small spatial scales is less understood, making the geographic scale at which intraspecific floral variation is examined important to evaluating causes of phenotypic divergence. In this study, we quantified phenotypic variation in the orchid Platanthera dilatata across 26 populations in coastal Southeast Alaska and compared this to edaphic and genetic variation at microsatellite loci. We sought to determine (1) if flower morphological variation is structured at smaller geographic scales, (2) the extent of genetic divergence in relation to phenotypic divergence, (3) the scale at which inter-population gene flow occurs, and (4) the relative importance of geographic distance and abiotic factors on population genetic structure. Two morphological groups were found to separate based on lip and spur length and are restricted to different habitats. Small-flowered forms occur in muskeg bogs, whereas large-flowered forms occur in fens and meadows, and rarely in sub-alpine habitat. Genetic analyses were concordant with the morphological clusters, except for four small-flowered populations that were genetically indistinguishable from large-flowered populations and considered to be introgressed. In fact, most populations exhibited some admixture, indicating incomplete reproductive isolation between the flower forms. Pollinators may partition phenotypes but also facilitate gene flow because short-tongued Noctuidae moths pollinate both phenotypes, but longer-tongued hawkmoths were only observed pollinating the large-flowered phenotype, which may strengthen phenotypic divergence. Nevertheless, pollinator movement between habitats could have lasting effects on neutral genetic variation. At this small spatial scale, population genetic structure is only associated with environmental distance, likely due to extensive seed and pollinator movement. While this study corroborates previous findings of cryptic genetic lineages and phenotypic divergence in P. dilatata, the small scale of examination provided greater understanding of the factors that may underlie divergence.
Evidencing success: Data requirements to model the impacts of long-term management of invasive squirrels
Authors: van der Waal Zelda , Mill Aileen C.
Published: March 2023

Established widespread populations of invasive vertebrates can be challenging to eradicate and for small to medium-sized vertebrates, such as squirrels, is often not deemed feasible. However, long-term trapping campaigns are necessary to limit spread or reduce impacts. The scale of trapping programmes is often limited by budgets that are not commensurate to the scale of the problem. On-going costs and fundraising are key factors used by decision makers to assess the feasibility of complete removal or long-term management options of established populations. Predicting the time and effort required to successfully manage Invasive Alien Species (IAS) remains a challenge, particularly where different strategies need to be employed across different spatial scales and habitat types, and in response to changing population densities. Statistical methods such as removal models can be applied to quantify population abundance during management operations and could inform planning of resource requirements. However, in practice, the lack of awareness of data requirements results in unsuited or non-standardized data collection. We present data from an invasive grey squirrel (Sciurus carolinensis) management project in the United Kingdom as a case study to illustrate common issues that impact on quantifying project outcomes. We focus on human and operational aspects of implementation and suggest ways of prioritizing analytical requirements. Insights consider conservation targets, data collection and operational design and may be of relevance to stakeholders, analysts, field operators and managers.
Changes in functional traits and diversity of typical alpine grasslands after a short-term trampling disturbance
Authors: Li Wei , Zheng Ting Dan , Cheng Xi Ping , He Shu Qiang
Published: March 2023

Alpine grassland ecosystem supports high diversity of terrestrial flora and fauna species. Despite the ecological importance and economic potential of this unique ecosystem type, it experiences increasing anthropogenic disturbances such as trampling, which impose negative impact on the health and integrity of alpine grasslands. Previous studies of trampling impact on alpine vegetation mainly focus on changes in vegetation cover and taxonomic diversity after trampling disturbance, but rarely test community-level responses of alpine vegetation to trampling from a functional trait perspective. Through the lens of vegetation functional traits, the present study evaluates the impacts of simulated trampling on typical alpine grasslands in Shangri-la, China. The results showed that although increased trampling intensity did not always lead to changes in functional diversity across all three experimental sites, characteristics of community-weighted mean trait values had consistently changed toward plant species with shorter height, reduced leaf area and lower leaf dry matter content, and such strong shifts in functional attributes may further affect ecosystem goods and services provided by alpine grasslands. Therefore, a functional trait approach can help us better understand the mechanisms that drive trait changes, function shifts and vegetation stability following anthropogenic disturbances.
Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease
Authors: Johnson Tyler B. , Brudvig Jon J. , Likhite Shibi , Pratt Melissa A. , White Katherine A. , Cain Jacob T. , Booth Clarissa D. , Timm Derek J. , Davis Samantha S. , Meyerink Brandon , Pineda Ricardo , Dennys-Rivers Cassandra , Kaspar Brian K. , Meyer Kathrin , Weimer Jill M.
Published: March 2023

CLN3 disease, caused by biallelic mutations in the CLN3 gene, is a rare pediatric neurodegenerative disease that has no cure or disease modifying treatment. The development of effective treatments has been hindered by a lack of etiological knowledge, but gene replacement has emerged as a promising therapeutic platform for such disorders. Here, we utilize a mouse model of CLN3 disease to test the safety and efficacy of a cerebrospinal fluid-delivered AAV9 gene therapy with a study design optimized for translatability. In this model, postnatal day one administration of the gene therapy virus resulted in robust expression of human CLN3 throughout the CNS over the 24-month duration of the study. A range of histopathological and behavioral parameters were assayed, with the therapy consistently and persistently rescuing a number of hallmarks of disease while being safe and well-tolerated. Together, the results show great promise for translation of the therapy into the clinic, prompting the launch of a first-in-human clinical trial (NCT03770572).
LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
Authors: Cesar Sergi , Coll Monica , Fiol Victoria , Fernandez-Falgueras Anna , Cruzalegui Jose , Iglesias Anna , Moll Isaac , Perez-Serra Alexandra , Martínez-Barrios Estefanía , Ferrer-Costa Carles , Olmo Bernat del , Puigmulè Marta , Alcalde Mireia , Lopez Laura , Pico Ferran , Berrueco Rubén , Brugada Josep , Zschaeck Irene , Natera-de Benito Daniel , Carrera-García Laura , Exposito-Escudero Jessica , Ortez Carlos , Nascimento Andrés , Brugada Ramon , Sarquella-Brugada Georgia , Campuzano Oscar
Published: March 2023

Background: Laminopathies are caused by rare alterations in LMNA, leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of patients diagnosed with LMNA-related muscular dystrophy to identify rare variants in alternative genes, thereby explaining phenotypic differences.

Methods: We analyzed 105 genes associated with muscular diseases by targeted sequencing in 26 pediatric patients of different countries, diagnosed with any LMNA-related muscular dystrophy. Family members were also clinically assessed and genetically analyzed.

Results: All patients carried a pathogenic rare variant in LMNA. Clinical diagnoses included Emery-Dreifuss muscular dystrophy (EDMD, 13 patients), LMNA-related congenital muscular dystrophy (L-CMD, 11 patients), and limb-girdle muscular dystrophy 1B (LGMD1B, 2 patients). In 9 patients, 10 additional rare genetic variants were identified in 8 genes other than LMNA. Genotype-phenotype correlation showed additional deleterious rare variants in five of the nine patients (3 L-CMD and 2 EDMD) with severe phenotypes.

Conclusion: Analysis f known genes related to muscular diseases in close correlation with personalized clinical assessments may help identify additional rare variants of LMNA potentially associated with early onset or most severe disease progression.
Development of a broadly active influenza intranasal vaccine adjuvanted with self-assembled particles composed of mastoparan-7 and CpG
Authors: Ontiveros-Padilla Luis , Batty Cole J. , Hendy Dylan A. , Pena Erik S. , Roque John A. , Stiepel Rebeca T. , Carlock Michael A. , Simpson Sean R. , Ross Ted M. , Abraham Soman N. , Staats Herman F. , Bachelder Eric M. , Ainslie Kristy M.
Published: March 2023

Currently licensed vaccine adjuvants offer limited mucosal immunity, which is needed to better combat respiratory infections such as influenza. Mast cells (MCs) are emerging as a target for a new class of mucosal vaccine adjuvants. Here, we developed and characterized a nanoparticulate adjuvant composed of an MC activator [mastoparan-7 (M7)] and a TLR ligand (CpG). This novel nanoparticle (NP) adjuvant was co-formulated with a computationally optimized broadly reactive antigen (COBRA) for hemagglutinin (HA), which is broadly reactive against influenza strains. M7 was combined at different ratios with CpG and tested for in vitro immune responses and cytotoxicity. We observed significantly higher cytokine production in dendritic cells and MCs with the lowest cytotoxicity at a charge-neutralizing ratio of nitrogen/phosphate = 1 for M7 and CpG. This combination formed spherical NPs approximately 200 nm in diameter with self-assembling capacity. Mice were vaccinated intranasally with COBRA HA and M7-CpG NPs in a prime–boost–boost schedule. Vaccinated mice had significantly higher antigen-specific antibody responses (IgG and IgA) in serum and mucosa compared with controls. Splenocytes from vaccinated mice had significantly increased cytokine production upon antigen recall and the presence of central and effector memory T cells in draining lymph nodes. Finally, co-immunization with NPs and COBRA HA induced influenza H3N2-specific HA inhibition antibody titers across multiple strains and partially protected mice from a challenge against an H3N2 virus. These results illustrate that the M7-CpG NP adjuvant combination can induce a protective immune response with a broadly reactive influenza antigen via mucosal vaccination.