bluuebunny/crossref_metadata_2025 huggingface dataset:
MICROHARDNESS OF CERAMIC MATERIALS BASED ON Ge-DOPED ARGYRODITE Ag6PS5I
Authors: Filep Michael , Pogodin Artem , Shender Iryna , Malakhovska Tetyana , Bilanych Vitaliy , Kokhan Oleksandr
Published: July 2023

This paper presents the preparation of mic­rocrystalline powders of Ag6PS5I, solid solutions of Ag6+xP1-xGexS5I (x = 0.25, 0.5, 0.75) and ceramic materials based on them. The microhardness of the ceramic samples was measured and the effect of heterovalent substitution of P5+↔Ge4+ on the mechanical properties of the studied samples was determined. The synthesis of initial Ag6PS5I and necessary for doping Ag7GeS5I was performed from the high purity elemental components (Ag, P, Ge, S) and previously synthesized binary AgI. Solid solutions of the Ag6+xP1-xGexS5I (x = 0.25, 0.5, 0.75) composition were synthesized from previously synthesised Ag6PS5I and Ag7GeS5I taken in stoichiometric amounts by a direct one-temperature method. As a result, polycrystalline bulk alloys of Ag6+xP1-xGexS5I solid were obtained. Microcrystalline Ag6+xP1-xGexS5I powders were obtained from the synthesized polycrystalline alloys by mechanical grinding (agate mortar). The powders were sieved through sieves with a pore size of 20 μm and 10 μm to obtain a fraction of crystallites with a size of 10-20 μm. The phase composition of the obtained powders was studied by means of XRD method. It has been found that the powder patterns of the studied samples are cha­racterized by the presence only of one system of reflexes corresponding to the face-centred cubic cell with SG F-43m. The resulting micropowders were pressed (P ~ 400 MPa) in the form of discs and annealed at 650 °С in vacuum quartz ampoules. The microhardness of the ceramics obtained in this way was measured by the Vickers method. For all ceramics, a decrease in the microhardness H is observed with an increase in the load P. This indicates that a direct size effect is observed for ceramics made on the basis of solid solutions of Ag6+xP1-xGexS5I. The obtained values of microhardness at a load of P > 1–1.5 N are independent of the load, which indicates the achievement of intrinsic hardness. Meyer's law was used to further analyze the microhardness and size effect of Ag6+xP1-xGexS5I solid solutions. The obtained values of the Meyer's index for Ag6+xP1-xGexS5I based ceramics are in the range n = 1.78 ÷ 1.81, which demonstrates the implementation of a direct size effect in these samples and indicates that the studied ceramics belong to soft materials. The concentration dependence of the microhardness indicates that an increase in the Germanium content in ceramic materials of solid solutions of Ag6+xP1-xGexS5I leads to a decrease in the microhardness of the materials.
İç ve Dış Politik Gelişmeler Işığında Erdoğan Döneminin Güvenlik Algısı
Authors: ÖZKAN Ahmet
Published: July 2023

Cumhuriyetin kuruluşundan 2002 yılında AK Parti’nin iktidara geldiği zaman dilimine kadar Türkiye, kendi iç dinamiklerine bağlı olarak toplumsal inşa sürecini tamamlamaya çalışmıştır. Ancak bu inşa süreci tek parti döneminde farklı 1950 sonrasında farklı araçlarla ve yaklaşımlarla sağlanmaya çalışılmıştır. Tek parti döneminde hayata geçirilen devrim ve inkılâplarla bu inşa süreci yürütülürken, tek parti sonrasında ise hemen hemen on senede bir yaşanan askerî darbelerle ulus inşa sürecinin sekteye uğramasına engel olunmaya çalışılmıştır. Bu döngü 90’lı yıllarda da kendisini göstermiş, bu girdaptan çıkışın Erdoğan liderliğindeki AK Parti iktidarıyla aşılabileceği halk tarafından tespit edilmiştir. Tespit edilmiştir dememizin sebebi oligarşik bürokrasi ve askeri vesayete karşı hukukun üstünlüğü ve AB normlarını önceleyerek politika geliştiren Erdoğan iktidarının defaatle halk tarafından iktidara taşınmış olmasıdır. Nitekim Erdoğan’a ve AK Parti’ye duyulan güven her seçimde sandık sonuçlarında görülmüş ve Erdoğan iktidarının sona erdirilmesinin sandıkla değil, alışılmış araçların kullanımıyla sağlanabileceği görüşü vesayet odakları tarafından benimsenmiş ve bu yönde adımların atılması beraberinde gelmiştir. Ne var ki Erdoğan liderliğindeki AK Parti, iç ve dış politikadaki problemleri Avrupa Birliği’ne üyelik, sistem değişikliği ve terörle etkin bir mücadele anlayışı göstererek aşmayı başarmıştır. Bu çalışma ile cumhuriyetin kuruluşundan günümüze kadar tarihsel bir analiz yapılacak ve iç ve dış politik gelişmeler ışığında Erdoğan döneminde güvenlik algısının nasıl dönüşüm yaşadığı analiz edilecektir.
Ak Parti Hükümetleri Yönetiminde İslami Finansın Gelişimi
Authors: HARUNOĞULLARI Erdal
Published: July 2023

Bu çalışma, 2002- 2023 dönemlerinde AK Parti hükümetlerinin Türkiye'de İslami finansın gelişimini için oynadığı rol incelenmiştir. Çalışmada, hükümet politikalarında katılım bankacılığı faaliyetlerinin gelişmesi için izlenilen yasal süreç, kamu katılım bankalarının kurulması, İslami finansla ilgili programların hükümet programlarına dâhil edilmesi ve İslami finansta Şeriat uyumunun standartlaştırılması için düzenleyici kurumlar ve danışma kurullarının oluşturulması gibi politika ve düzenlemeler ele alınacaktır. Ayrıca çalışma, İstanbul'un küresel bir finans merkezi olması hedefi açısından büyük potansiyele sahip olan katılım bankacılığı sektörünün gelişimini sağlayan politika ve düzenlemeleri incelemektedir. Cumhurbaşkanlığı Yıllık Programları analiz edilerek TKBB (Türkiye Katılım Bankaları Birliği) ve BDDK (Bankacılık Düzenleme ve Denetleme Kurumu) verileri ile Türkiye’de İslami finansın gelişimi değerlendirilecektir. Ayrıca, çalışmada, Türkiye'nin küresel İslami finans sektöründe lider bir oyuncu olma potansiyelini SWOT analizi yoluyla ele alınacaktır.
EFFECT OF IMMERSION TYPE III GYPSUM IN SODIUM HYPOCHLORITE AND POVIDONE-IODINE SOLUTIONS ON THE NUMBER OF CANDIDA ALBICANS COLONIES
Authors: Rizal Moh. Basroni , Andriani Dwi , Putra Yoga Pratama
Published: July 2023

Introduction: Cross-infection is the transfer of microorganisms that can occur from individual to individual or to object. Candida albicans is one of the infectious pathogens that can cause cross-infection in dentistry. One example is the manufacture of working models of gypsum material, which can cause cross-infection from patients to dentists or technicians, so it is necessary to control infection by means of    disinfection    of    type    III    gypsum     material     work models. Objective: To determine the effectiveness of soaking type III Gypsum in a 0.5% Sodium hypochlorite and 2% Povidone Iodine solution against the growth of Candida albicans. Methods: A laboratory experiment with a total of 21 samples, consisting of 7 samples for each group. The sample is made of a type III gypsum plate measuring 2 x 1 x 0.5 cm. The sample consisted of 3 groups: treatment 1, treatment 2, and treatment 3. The study used the diffusion method. Gypsum plate type III was contaminated with Candida albicans and then immersed in a solution of sterile distilled water (C), 0.5% sodium hypochlorite (P1), and 2% povidone-iodine (P2). The soaking results were planted in SDA media, incubated for 2x24 hours, and then counted using a colony counter. The data were analyzed using Kruskal- Wallis and Mann-Whitney post hoc analyses. Results: In the Kruskal- Wallis analysis of significance (p), between each group, there was a significant difference (p<0.05). The Mann-Whitney post hoc analysis test showed a correlation between group K and P1 and P2 (p<0.05). Conclusion: 0.5% Sodium Hypochlorite and 2% Povidone Iodine solutions are effective as disinfectants using the immersion method in Type III Gypsum against the growth of Candida albicans.
Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment with delandistrogene moxeparvovec gene therapy in individuals with Duchenne muscular dystrophy
Authors: Mendell Jerry R. , Shieh Perry B. , McDonald Craig M. , Sahenk Zarife , Lehman Kelly J. , Lowes Linda P. , Reash Natalie F. , Iammarino Megan A. , Alfano Lindsay N. , Sabo Brenna , Woods Jeremy D. , Skura Christy L. , Mao Howard C. , Staudt Loretta A. , Griffin Danielle A. , Lewis Sarah , Wang Shufang , Potter Rachael A. , Singh Teji , Rodino-Klapac Louise R.
Published: July 2023

Introduction: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy designed for targeted expression of SRP-9001 dystrophin protein, a shortened dystrophin retaining key functional domains of the wild-type protein.

Methods: This Phase 2, double-blind, two-part (48 weeks per part) crossover study (SRP-9001-102 [Study 102]; NCT03769116) evaluated delandistrogene moxeparvovec in patients, aged ≥4 to <8 years with Duchenne muscular dystrophy. Primary endpoints (Part 1) were change from baseline (CFBL) in SRP-9001 dystrophin expression (Week 12), by Western blot, and in North Star Ambulatory Assessment (NSAA) score (Week 48). Safety assessments included treatment-related adverse events (TRAEs). Patients were randomized and stratified by age to placebo (n = 21) or delandistrogene moxeparvovec (n = 20) and crossed over for Part 2.

Results: SRP-9001 dystrophin expression was achieved in all patients: mean CFBL to Week 12 was 23.82% and 39.64% normal in Parts 1 and 2, respectively. In Part 1, CFBL to Week 48 in NSAA score (least-squares mean, LSM [standard error]) was +1.7 (0.6) with treatment versus +0.9 (0.6) for placebo; p = 0.37. Disparity in baseline motor function between groups likely confounded these results. In 4- to 5-year-olds with matched baseline motor function, CFBL to Week 48 in NSAA scores was significantly different (+2.5 points; p = 0.0172), but not significantly different in 6-to-7-year-olds with imbalanced baseline motor function (−0.7 points; p = 0.5384). For patients treated with delandistrogene moxeparvovec in Part 2, CFBL to Week 48 in NSAA score was +1.3 (2.7), whereas for those treated in Part 1, NSAA scores were maintained. As all patients in Part 2 were exposed to treatment, results were compared with a propensity-score-weighted external control (EC) cohort. The LSM difference in NSAA score between the Part 2 treated group and EC cohort was statistically significant (+2.0 points; p = 0.0009). The most common TRAEs were vomiting, decreased appetite, and nausea. Most occurred within the first 90 days and all resolved.

Discussion: Results indicate robust expression of SRP-9001 dystrophin and overall stabilization in NSAA up to 2 years post-treatment. Differences in NSAA between groups in Part 1 were not significant for the overall population, likely because cohorts were stratified only by age, and other critical prognostic factors were not well matched at baseline.
Advances in ecotechnological methods for diffuse nutrient pollution control: wicked issues in agricultural and urban watersheds
Authors: Nsenga Kumwimba Mathieu , Zhu Bo , Stefanakis Alexandros I. , Ajibade Fidelis O. , Dzakpasu Mawuli , Soana Elisa , Wang Tao , Arif Muhammad , Kavidia Muyembe Diana , Agboola Temitope Deborah
Published: July 2023

Considerable time and funding have been committed to tackling nonpoint source (NPS) pollution in agricultural and urban watersheds . Notwithstanding all these efforts, the water quality in many AUWs has not significantly improved. Diffuse nutrient pollution involves the movement of these pollutants between soil and water. Excessive diffuse pollution has been accepted as one of the main causes of failure to attain favorable environmental conditions in freshwater systems. Recently, several technologies and practices have been implemented to manage diffuse pollution, namely: a) source reduction, b) pollutant retention over the movement process; c) nutrient recycling, and d) purification and restoration of the eutrophic water bodies. This paper synthesized the existing knowledge of key methods to tackle diffuse pollution from AUWs. Furthermore, the predominant purification mechanisms and impacting factors are explored, allowing a comprehensive and critical understanding of different control strategies to improve the management of diffuse pollution. Therefore, potential approaches for strengthening the performance of control technologies for diffuse pollution treatment and remediation are discussed. Although adopting source reduction strategies (e.g., the “4R” approach: right rate, right time, right source, and right placement of nutrients) could efficiently decrease surface runoff and pollutant levels, they may not stop runoff from entering nearby streams. Consequently, comprehensive treatment of agricultural runoff still requires extra process retention strategies. Overall, the findings of this paper showed that treatment system design and operational and environmental factors played crucial but variable roles in diffuse pollution treatment. Moreover, the results showed that combining or integrating constructed wetlands with other control technologies could enhance the comprehensive purification of diffuse pollution compared to using a single method. This review proposes a systematic approach for diffuse pollution control based on three components (water, soil and microbiota) and maximizing the regulating services of agroecosystems via land use/cover types. The current review contributes to the documentation of existing research trends. It sheds light on diffuse pollution control approaches in AUWs, and further encourages the development of this vital field.
Diffusion during collective turns in bird flocks under predation
Authors: Papadopoulou Marina , Hildenbrandt Hanno , Hemelrijk Charlotte K.
Published: July 2023

Moving in groups offers animals protection against predation. When under attack, grouped individuals often turn collectively to evade a predator, which sometimes makes them rapidly change their relative positions in the group. In bird flocks in particular, the quick reshuffling of flock members confuses the predator, challenging its targeting of a single individual. This confusion is considered to be greater when the internal structure of the group changes faster (i.e. the ‘diffusion’ of the group is higher). Diffusion may increase when individual birds turn collectively with equal radii (same angular velocity) but not when individuals keep their paths parallel (by adjusting their speed). However, how diffusion depends on individual behaviour is not well known. When under attack, grouping individuals change the way they interact with each other, referred to as ‘alarmed coordination’ (e.g., increase their reaction frequency or their cohesion tendency), but the effect of such changes on collective turning is unknown. Here, we aimed to gain an understanding of the dynamics of collective turning in bird flocks. First, to investigate the relation between alarmed coordination and flock diffusion, we developed an agent-based model of bird flocks. Second, to test how diffusion relates to collective turns with equal-radii and parallel-paths, we developed a metric of the deviation from these two types. Third, we studied collective turning under predation empirically, by analysing the GPS trajectories of pigeons in small flocks pursued by a RobotFalcon. As a measure of diffusion, we used the instability of neighbours: the rate with which the closest neighbours of a flock member are changing. In our simulations, we showed that this instability increases with group size, reaction frequency, topological range, and cohesion tendency and that the relation between instability of neighbours and the deviation from the two turning types depends in often counter-intuitive ways on these coordination specifics. Empirically, we showed that pigeons turn collectively with less diffusion than starlings and that their collective turns are in between those with equal-radii and parallel-paths. Overall, our work provides a framework for studying collective turning across species.
Pre-transplant immune profile defined by principal component analysis predicts acute rejection after kidney transplantation
Authors: Gaiffe Emilie , Colladant Mathilde , Desmaret Maxime , Bamoulid Jamal , Leroux Franck , Laheurte Caroline , Brouard Sophie , Giral Magali , Saas Philippe , Courivaud Cécile , Degauque Nicolas , Ducloux Didier
Published: July 2023

Background

Acute rejection persists as a frequent complication after kidney transplantation. Defining an at-risk immune profile would allow better preventive approaches.

Methods

We performed unsupervised hierarchical clustering analysis on pre-transplant immunological phenotype in 1113 renal transplant recipients from the ORLY-EST cohort.

Results

We identified three immune profiles correlated with clinical phenotypes. A memory immune cluster was defined by memory CD4+T cell expansion and decreased naïve CD4+T cell. An activated immune cluster was characterized by an increase in CD8+T cells and a decreased CD4/CD8 ratio. A naïve immune cluster was mainly defined by increased naïve CD4+T cells. Patients from the memory immune profile tend to be older and to have diabetes whereas those from the activated immune profile were younger and more likely to have pre-transplant exposure to CMV. Patients from the activated immune profile were more prone to experience acute rejection than those from other clusters [(HR=1.69, 95%IC[1.05-2.70], p=0.030) and (HR=1.85; 95%IC[1.16-3.00], p=0.011). In the activated immune profile, those without previous exposure to CMV (24%) were at very high risk of acute rejection (27 vs 16%, HR=1.85; 95%IC[1.04-3.33], p=0.039).

Conclusion

Immune profile determination based on principal component analysis defines clinically different sub-groups and discriminate a population at high-risk of acute rejection.
Cutaneous immune-related adverse events to immune checkpoint inhibitors: from underlying immunological mechanisms to multi-omics prediction
Authors: Cao Ting , Zhou Xuyang , Wu Xingbiao , Zou Ying
Published: July 2023

The development of immune checkpoint inhibitors (ICIs) has dramatically altered the landscape of therapy for multiple malignancies, including urothelial carcinoma, non-small cell lung cancer, melanoma and gastric cancer. As part of their anti-tumor properties, ICIs can enhance susceptibility to inflammatory side effects known as immune-related adverse events (irAEs), in which the skin is one of the most commonly and rapidly affected organs. Although numerous questions still remain unanswered, multi-omics technologies have shed light into immunological mechanisms, as well as the correlation between ICI-induced activation of immune systems and the incidence of cirAE (cutaneous irAEs). Therefore, we reviewed integrated biological layers of omics studies combined with clinical data for the prediction biomarkers of cirAEs based on skin pathogenesis. Here, we provide an overview of a spectrum of dermatological irAEs, discuss the pathogenesis of this “off-tumor toxicity” during ICI treatment, and summarize recently investigated biomarkers that may have predictive value for cirAEs via multi-omics approach. Finally, we demonstrate the prognostic significance of cirAEs for immune checkpoint blockades.
Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma
Authors: Secondino Simona , Pedrazzoli Paolo , Basso Sabrina , Bossi Paolo , Bianco Alba , Imarisio Ilaria , Pagani Anna , De Cicco Marica , Muscianisi Stella , Casanova Michela , Morosi Carlo , Bergamini Cristiana , Benazzo Marco , Cossu Rocca Maria , Perotti Cesare , Baldanti Fausto , Zecca Marco , Licitra Lisa F. , Comoli Patrizia
Published: July 2023

Background

Refractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.

Patients and Methods

Between 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.

Results

All patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome.

Conclusions

Autologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial.
Extended cleavage specificities of human granzymes A and K, two closely related enzymes with conserved but still poorly defined functions in T and NK cell-mediated immunity
Authors: Aybay Erdem , Ryu Jinhye , Fu Zhirong , Akula Srinivas , Enriquez Erika Mendez , Hallgren Jenny , Wernersson Sara , Olsson Anna-Karin , Hellman Lars
Published: July 2023

Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTL) and natural killer cells (NK). Granzyme A is the most abundant of the different granzymes (gzms) expressed by these two cell types. Gzms A and K are found in all jawed vertebrates and are the most well conserved of all hematopoietic serine proteases. Their potential functions have been studied extensively for many years, however, without clear conclusions. Gzm A was for many years thought to serve as a key component in the defense against viral infection by the induction of apoptosis in virus-infected cells, similar to gzm B. However, later studies have questioned this role and instead indicated that gzm A may act as a potent inducer of inflammatory cytokines and chemokines. Gzms A and K form clearly separate branches in a phylogenetic tree indicating separate functions. Transcriptional analyses presented here demonstrate the presence of gzm A and K transcripts in both CD4+ and CD8+ T cells. To enable screening for their primary biological targets we have made a detailed analysis of their extended cleavage specificities. Phage display analysis of the cleavage specificity of the recombinant enzymes showed that both gzms A and K are strict tryptases with high selectivity for Arg over Lys in the P1 position. The major differences in the specificities of these two enzymes are located N-terminally of the cleavage site, where gzm A prefers small amino acids such as Gly in the P3 position and shows a relatively relaxed selectivity in the P2 position. In contrast, gzm K prefers large amino acids such as Phe, Tyr, and Trp in both the P2 and P3 positions and does not tolerate negatively charged residues in the P2 position. This major distinction in extended specificities is likely reflected also in preferred in vivo targets of these two enzymes. This information can now be utilized for high-precision screening of primary targets for gzms A and K in search of their highly conserved but still poorly defined functions in vertebrate immunity.
The role of CD8+ T cells in endometriosis: a systematic review
Authors: Kisovar Ana , Becker Christian M. , Granne Ingrid , Southcombe Jennifer H.
Published: July 2023

Background

Endometriosis is a chronic disease affecting 6–10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown. We systematically evaluated the literature on the CD8 T in peripheral blood and endometriosis-associated tissues to determine the current understanding of their pathophysiological and clinical relevance in the disease and associated conditions (e.g. infertility and pelvic pain).

Methods

Four databases were searched (MEDLINE, EMBASE, Web of Science, CINAHL), from database inception until September 2022, for papers written in the English language with database-specific relevant terms/free-text terms from two categories: CD8 T cells and endometriosis. We included peer-reviewed papers investigating CD8 T cells in peripheral blood and endometriosis-associated tissues of patients with surgically confirmed endometriosis between menarche and menopause, and animal models with oestrous cycles. Studies enrolling participants with other gynaecological pathologies (except uterine fibroids and tubal factor infertility used as controls), cancer, immune diseases, or taking immune or hormonal therapy were excluded.

Results

28 published case-control studies and gene set analyses investigating CD8 T cells in endometriosis were included. Data consistently indicate that CD8 T cells are enriched in endometriotic lesions in comparison to eutopic endometrium, with no differences in peripheral blood CD8 T populations between patients and healthy controls. Evidence on CD8 T cells in peritoneal fluid and eutopic endometrium is conflicting. CD8 T cell cytotoxicity was increased in the menstrual effluent of patients, and genomic analyses have shown a clear trend of enriched CD8 T effector memory cells in the eutopic endometrium of patients.

Conclusion

Literature on CD8 T cells in endometriosis-associated tissues is inconsistent. Increased CD8 T levels are found in endometriotic lesions, however, their activation potential is understudied in all relevant tissues. Future research should focus on identifying clinically relevant phenotypes to support the development of non-invasive diagnostic and treatment strategies.

Systematic Review Registration

PROSPERO identifier CRD42021233304
Effect of postoperative residual astigmatism on visual outcomes after trifocal intraocular lens implantation
Authors: Zhang Limei , Shen Wenqian , Shen Jiying , Wang Min , Ni Shuang , Guo Haike , Yang Jin
Published: July 2023

Purpose

The aim of this study was to evaluate the effect of residual astigmatism on postoperative visual outcomes after trifocal intraocular lens implantation.

Methods

In this prospective observational study, we divided 156 eyes into two groups according to postoperative astigmatism measured by subjective optometry and followed them up for 3 months. Visual acuity, modulation transfer function (MTF) curves, Strehl ratio (SR), Visual Function Index-14 scores, and photic phenomena were compared.

Results

Linear regression analysis revealed a weak correlation between residual astigmatism and uncorrected distance visual acuity (UDVA) (r = 0.190, P = 0.016) at 3 months and a significant between-group difference at 1- and 3-month postoperative UDVA (P = 0.038, P = 0.018, respectively). MTF curve values and SR (MTF-10 total, MTF-10 cornea, MTF-30 total, MTF-30 cornea, SR Total, and SR cornea) were significantly worse (P < 0.001), and the Visual Function Index-14 scores were lower in the 0.5 < astigmatism ≤ 1.25 D group (P < 0.05) than in the astigmatism ≤ 0.5 D group. No significant differences were found in the frequency, severity, and bothersomeness of photic phenomena (P > 0.05).

Conclusion

Postoperative residual astigmatism affects the UDVA of the trifocal intraocular lens-implanted eyes. Although we found no significant differences in uncorrected intermediate and near visual acuity, both objective and subjective visual quality were affected, suggesting the need for surgical planning when the anticipated postoperative astigmatism is >0.5 D.
Associations between adiposity, diabetes, lifestyle factors and the risk of gliomas
Authors: Liu Xiaozhi , Wang Yang , Wang Yuxiang , Zhao Jincheng , Shi Wanchao , Zhao Yujun , Chen Lei , Wu Lei
Published: July 2023

Background

Despite numerous observational studies linking adiposity, diabetes, and lifestyle factors with gliomas, the causal associations between them remain uncertain.

Methods

This study aimed to use two-sample Mendelian randomization (MR) analysis to investigate whether these associations are causal. Specifically, independent genetic variants in body mass index (BMI), waist circumference (WC), type 2 diabetes (T2D), smoking, alcohol, and coffee consumption were extracted from the published genome-wide association studies (GWASs) with genome-wide significance. The corresponding summary-level data for gliomas were available from a GWAS of 1,856 cases and 4,955 controls of European descent from the GliomaScan consortium. Additionally, glioma pathogenesis-related protein 1 data were used for validation, and Radial MR analysis was conducted to examine the potential outlier single-nucleotide polymorphisms (SNPs).

Results

One standard deviation (SD) increase in BMI had an odds ratio (OR) of 1.392 (95% confidence interval (CI), 0.935–2.071) for gliomas, while one SD increase in WC had an OR of 0.967 (95% CI, 0.547–1.710). For T2D, a one-unit increase in log-transformed OR had an OR of 0.923 (95% CI, 0.754–1.129). The prevalence of smoking initiation had an OR of 1.703 (95% CI, 0.871–3.326) for gliomas, while the prevalence of alcohol intake frequency had an OR of 0.806 (95% CI, 0.361–1.083), and the prevalence of coffee intake had an OR of 0.268 (95% CI, 0.033–2.140) for gliomas.

Conclusion

This study provides evidence that adiposity, T2D, smoking, alcohol drinking, and coffee intake do not play causal roles in the development of gliomas. The findings highlight the importance of reconsidering causal relationships in epidemiological research to better understand the risk factors and prevention strategies for gliomas.
Inhibitors of riboflavin biosynthetic pathway enzymes as potential antibacterial drugs
Authors: Islam Zeyaul , Kumar Pankaj
Published: July 2023

Multiple drug resistance is the main obstacle in the treatment of bacterial diseases. Resistance against antibiotics demands the exploration of new antimicrobial drug targets. A variety of in silico and genetic approaches show that the enzymes of the riboflavin biosynthetic pathway are crucial for the survival of bacteria. This pathway is absent in humans thus enzymes of the riboflavin biosynthetic pathway are emerging drug targets for resistant pathogenic bacterial strains. Exploring the structural details, their mechanism of action, intermediate elucidation, and interaction analysis would help in designing suitable inhibitors of these enzymes. The riboflavin biosynthetic pathway consists of seven distinct enzymes, namely, 3,4-dihydroxy-2-butanone 4-phosphate synthase, GTP cyclohydrolase II, pyrimidine deaminase/reductase, phosphatase, lumazine synthase, and riboflavin synthase. The present review summarizes the research work that has been carried out on these enzymes in terms of their structures, active site architectures, and molecular mechanism of catalysis. This review also walks through small molecule inhibitors that have been developed against several of these enzymes.
Association between physical activity and episodic memory and the moderating effects of the apolipoprotein E ε4 allele and age
Authors: Lee Boung Chul , Choe Young Min , Suh Guk-Hee , Choi Ihn-Geun , Kim Hyun Soo , Hwang Jaeuk , Yi Dahyun , Kim Jee Wook
Published: July 2023

Background

An abundance of evidence indicates that physical activity may protect against Alzheimer’s disease (AD) and related cognitive decline. However, little is known about the association between physical activity and AD-related cognitive decline according to age and the apolipoprotein E (APOE) ε4 allele (APOE4) as major risk factors. Therefore, we examined whether age and APOE4 status modulate the effects of physical activity on episodic memory as AD-related cognition in non-demented older adults.

Methods

We enrolled 196 adults aged between 65 and 90 years, with no dementia. All participants underwent comprehensive clinical assessments including physical activity evaluation and APOE genotyping. The AD-related cognitive domain was assessed by the episodic memory, as the earliest cognitive change in AD, and non-memory cognition for comparative purposes. Overall cognition was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery.

Results

We found significant physical activity × age and physical activity × APOE4 interaction effects on episodic memory. Subgroup analyses indicated that an association between physical activity and increased episodic memory was apparent only in subjects aged > 70 years, and in APOE4-positive subjects.

Conclusion

Our findings suggest that physical activity has beneficial effects on episodic memory, as an AD-related cognitive domain, in individuals aged > 70 years and in APOE4-positive individuals. Physicians should take age and APOE4 status account into when recommending physical activity to prevent AD-related cognitive decline.
Statistically significant features improve binary and multiple Motor Imagery task predictions from EEGs
Authors: Degirmenci Murside , Yuce Yilmaz Kemal , Perc Matjaž , Isler Yalcin
Published: July 2023

In recent studies, in the field of Brain-Computer Interface (BCI), researchers have focused on Motor Imagery tasks. Motor Imagery-based electroencephalogram (EEG) signals provide the interaction and communication between the paralyzed patients and the outside world for moving and controlling external devices such as wheelchair and moving cursors. However, current approaches in the Motor Imagery-BCI system design require effective feature extraction methods and classification algorithms to acquire discriminative features from EEG signals due to the non-linear and non-stationary structure of EEG signals. This study investigates the effect of statistical significance-based feature selection on binary and multi-class Motor Imagery EEG signal classifications. In the feature extraction process performed 24 different time-domain features, 15 different frequency-domain features which are energy, variance, and entropy of Fourier transform within five EEG frequency subbands, 15 different time-frequency domain features which are energy, variance, and entropy of Wavelet transform based on five EEG frequency subbands, and 4 different Poincare plot-based non-linear parameters are extracted from each EEG channel. A total of 1,364 Motor Imagery EEG features are supplied from 22 channel EEG signals for each input EEG data. In the statistical significance-based feature selection process, the best one among all possible combinations of these features is tried to be determined using the independent t-test and one-way analysis of variance (ANOVA) test on binary and multi-class Motor Imagery EEG signal classifications, respectively. The whole extracted feature set and the feature set that contain statistically significant features only are classified in this study. We implemented 6 and 7 different classifiers in multi-class and binary (two-class) classification tasks, respectively. The classification process is evaluated using the five-fold cross-validation method, and each classification algorithm is tested 10 times. These repeated tests provide to check the repeatability of the results. The maximum of 61.86 and 47.36% for the two-class and four-class scenarios, respectively, are obtained with Ensemble Subspace Discriminant among all these classifiers using selected features including only statistically significant features. The results reveal that the introduced statistical significance-based feature selection approach improves the classifier performances by achieving higher classifier performances with fewer relevant components in Motor Imagery task classification. In conclusion, the main contribution of the presented study is two-fold evaluation of non-linear parameters as an alternative to the commonly used features and the prediction of multiple Motor Imagery tasks using statistically significant features.
Emotional brain network decoded by biological spiking neural network
Authors: Xu Hubo , Cao Kexin , Chen Hongguang , Abudusalamu Awuti , Wu Wei , Xue Yanxue
Published: July 2023

Introduction

Emotional disorders are essential manifestations of many neurological and psychiatric diseases. Nowadays, researchers try to explore bi-directional brain-computer interface techniques to help the patients. However, the related functional brain areas and biological markers are still unclear, and the dynamic connection mechanism is also unknown.

Methods

To find effective regions related to different emotion recognition and intervention, our research focuses on finding emotional EEG brain networks using spiking neural network algorithm with binary coding. We collected EEG data while human participants watched emotional videos (fear, sadness, happiness, and neutrality), and analyzed the dynamic connections between the electrodes and the biological rhythms of different emotions.

Results

The analysis has shown that the local high-activation brain network of fear and sadness is mainly in the parietal lobe area. The local high-level brain network of happiness is in the prefrontal-temporal lobe-central area. Furthermore, the α frequency band could effectively represent negative emotions, while the α frequency band could be used as a biological marker of happiness. The decoding accuracy of the three emotions reached 86.36%, 95.18%, and 89.09%, respectively, fully reflecting the excellent emotional decoding performance of the spiking neural network with self- backpropagation.

Discussion

The introduction of the self-backpropagation mechanism effectively improves the performance of the spiking neural network model. Different emotions exhibit distinct EEG networks and neuro-oscillatory-based biological markers. These emotional brain networks and biological markers may provide important hints for brain-computer interface technique exploration to help related brain disease recovery.
Improved spatial–temporal graph convolutional networks for upper limb rehabilitation assessment based on precise posture measurement
Authors: Bai Jing , Wang Zhixian , Lu Xuanming , Wen Xiulan
Published: July 2023

After regular rehabilitation training, paralysis sequelae can be significantly reduced in patients with limb movement disorders caused by stroke. Rehabilitation assessment is the basis for the formulation of rehabilitation training programs and the objective standard for evaluating the effectiveness of training. However, the quantitative rehabilitation assessment is still in the experimental stage and has not been put into clinical practice. In this work, we propose improved spatial-temporal graph convolutional networks based on precise posture measurement for upper limb rehabilitation assessment. Two Azure Kinect are used to enlarge the angle range of the visual field. The rigid body model of the upper limb with multiple degrees of freedom is established. And the inverse kinematics is optimized based on the hybrid particle swarm optimization algorithm. The self-attention mechanism map is calculated to analyze the role of each upper limb joint in rehabilitation assessment, to improve the spatial-temporal graph convolution neural network model. Long short-term memory is built to explore the sequence dependence in spatial-temporal feature vectors. An exercise protocol for detecting the distal reachable workspace and proximal self-care ability of the upper limb is designed, and a virtual environment is built. The experimental results indicate that the proposed posture measurement method can reduce position jumps caused by occlusion, improve measurement accuracy and stability, and increase Signal Noise Ratio. By comparing with other models, our rehabilitation assessment model achieved the lowest mean absolute deviation, root mean square error, and mean absolute percentage error. The proposed method can effectively quantitatively evaluate the upper limb motor function of stroke patients.
Rab11a Regulates the Development of Cilia and Establishment of Planar Cell Polarity in Mammalian Vestibular Hair Cells
Authors: Chen Bin-Jun , Qian Xiao-qing , Yang Xiao-yu , Jiang Tao , Wang Yan-mei , Lyu Ji-han , Chi Fang-lu , Chen Ping , Ren Dong-dong
Published: July 2023

Vestibular organs have unique planar cell polarity (Figure 1A), and their normal development and function are dependent on the regular polarity of cilia (Figure 1B) requires. Rab11a is a small G protein that participates in the transportation of intracellular and extracellular materials required for polarity formation; however, our understanding of the mechanisms of the actions of Rab11a in vestibular organs is limited. Here, we showed that the general shape of the utricle was abnormal in Rab11aCKO/CKO mice. These mice also showed abnormal morphology of the stereocilia bundles, which were reduced in both length and number, as well as disturbed tissue-level polarity. Rab11a affected the distribution of polarity proteins in the vestibular organs, indicating that the normal development of cilia requires Rab11a and intraflagellar transportation. Furthermore, small G protein migration works together with intraflagellar transportation in the normal development of cilia.
A single-arm study design with non-inferiority and superiority time-to-event endpoints: a tool for proof-of-concept and de-intensification strategies in breast cancer
Authors: Sampayo-Cordero Miguel , Miguel-Huguet Bernat , Malfettone Andrea , López-Miranda Elena , Gion María , Abad Elena , Alcalá-López Daniel , Pérez-Escuredo Jhudit , Pérez-García José Manuel , Llombart-Cussac Antonio , Cortés Javier
Published: July 2023

De-escalation trials in oncology evaluate therapies that aim to improve the quality of life of patients with low-risk cancer by avoiding overtreatment. Non-inferiority randomized trials are commonly used to investigate de-intensified regimens with similar efficacy to that of standard regimens but with fewer adverse effects (ESMO evidence tier A). In cases where it is not feasible to recruit the number of patients needed for a randomized trial, single-arm prospective studies with a hypothesis of non-inferiority can be conducted as an alternative. Single-arm studies are also commonly used to evaluate novel treatment strategies (ESMO evidence tier B). A single-arm design that includes both non-inferiority and superiority primary objectives will enable the ranking of clinical activity and other parameters such as safety, pharmacokinetics, and pharmacodynamics data. Here, we describe the statistical principles and procedures to support such a strategy. The non-inferiority margin is calculated using the fixed margin method. Sample size and statistical analyses are based on the maximum likelihood method for exponential distributions. We present example analyses in metastatic and adjuvant settings to illustrate the usefulness of our methodology. We also explain its implementation with nonparametric methods. Single-arm designs with non-inferiority and superiority analyses are optimal for proof-of-concept and de-escalation studies in oncology.
Factors influencing age of common allergen introduction in early childhood
Authors: Marget Michael , Virkud Yamini V. , Shreffler Wayne G. , Martin Victoria M. , Yuan Qian
Published: July 2023

Objectives

We evaluated factors influencing the timing of allergen introduction in the U.S., including updated peanut introduction guidelines.

Study design

The Gastrointestinal Microbiome and Allergic Proctocolitis (GMAP) study is a prospective observational cohort in suburban Massachusetts. Infants' caregivers enrolled between 2014 and 2017, and they reported when they introduced common allergens to their child. Multivariable linear and survival regression analyses were used to examine factors influencing time of introduction of allergens.

Results

By 9 months, children old enough to be potentially affected by NIAID's 2017 peanut introduction guidelines were more often introduced to peanut than children enrolled well before guidelines publication [54% vs. 42%, OR: 1.63, CI: (1.03, 2.57), P = 0.03]. At any given time, Black children were 73% [HR: 0.27, CI: (0.11, 0.69), P = 0.006] less likely to be introduced to peanut as early as White children. Asian children were, respectively, 36% [HR: 0.64, CI: (0.47, 0.86), P = 0.003] and 26% [HR: 0.74, CI: (0.55, 0.97), P = 0.03] less likely to be introduced to peanut and egg as early as White children. A first child was 27% [HR: 1.27, CI: (1.04, 1.56), P = 0.02] more likely to have been introduced to peanut earlier than a non-first child. There was no association between age of introduction and sex, gestational age, family history of food allergy, or other allergic comorbidities.

Conclusion

Updated introduction guidelines, race, and birth order all influenced earlier introduction of peanut. Further studies to evaluate current practices for allergen introduction with a focus on potential disparities are needed.
COVID-19 associates with semen inflammation and sperm quality impairment that reverses in the short term after disease recovery
Authors: Martinez María Sol , Ferreyra Fernando Nicolás , Paira Daniela Andrea , Rivero Virginia Elena , Olmedo José Javier , Tissera Andrea Daniela , Molina Rosa Isabel , Motrich Rubén Darío
Published: July 2023

Introduction: COVID-19 exerts deleterious effects on the respiratory, cardiovascular, gastrointestinal, and central nervous systems, causing more severe disease in men than in women. However, cumulative reported data about the putative consequences on the male reproductive tract and fertility are controversial. Furthermore, the long-term effects of SARS-CoV-2 infection are still uncertain.

Methods: In this study, we prospectively evaluated levels of inflammatory cytokines and leukocytes in semen and sperm quality parameters in a cohort of 231 reproductive-aged male patients, unvaccinated, who had recovered from mild or severe COVID-19 and in 62 healthy control individuals. Sperm quality was assessed early (less than 3 months) and long (more than 3 and up to 6 months) after having COVID-19. Interestingly, and unlike most reported studies, available extensive background and baseline data on patients’ sperm quality allowed performing a more accurate analysis of COVID-19 effects on sperm quality.

Results: Significantly higher levels of IL-1β, TNF and IFNγ were detected in semen from patients recently recovered from mild and/or severe COVID-19 with respect to control individuals indicating semen inflammation. Moreover, patients recovered from mild and/or severe COVID-19 showed significantly reduced semen volume, lower total sperm counts, and impaired sperm motility and viability. Interestingly, all observed alterations returned to baseline values after 3 or more months after disease recovery.

Discussion: These results indicate that COVID-19 associates with semen inflammation and impaired semen quality early after disease. However, long COVID-19 seems not to include long-term detrimental consequences on male fertility potential since the observed alterations were reversible after 1-2 spermatogenesis cycles. These data constitute compelling evidence allowing a better understanding of COVID-19 associated sequelae, fundamental for semen collection in assisted reproduction.