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Background The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.Methods We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)tau and AT(N)NfL). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.Results We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)tau and AT(N)NfL classifications. When we used t-tau as the N marker (AT(N)tau), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)NfL). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)tau and AT(N)NfL classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)tau classification, but not in the AT(N)NfL classification.Conclusions AT(N)tau and AT(N)NfL in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.

Nonvesicular extracellular RNA (nex-RNA) that are not packed in extracellular vesicles is detected outside the cell, but it is poorly understood. Here the authors report that nex-RNA is captured by a zinc finger protein and transported to the nucleus to enhance antimetastatic characters of the cell.

Background and Objectives: The capability to cause invasive infection, multi-drug resistance, and health care-associated outbreaks of Candida auris have made it a pathogen of great concern. Estimating how many patients in our intensive care unit had C. auris colonization and what characteristics put patients at risk for having Candida spp. colonization were the primary goals of the study. Materials and Methods: Swabs from axilla and groin were collected from 229 patients getting admitted to the ICU. Samples were inoculated into CHROMagarTM Candida Plus medium. Colonies presumptively identified as C. auris by the presence of light blue with blue halo and were confirmed by VITEK-2. Results: Our study showed that only one patient was colonized with C. auris. A total of 47 (20.5%) patients were colonized with Candida spp., of which Candida parapislosis was the predominant organism. History of antibiotic use and cerebrovascular accident were independent risk factors in Candida colonization. Conclusion: Active screening for Candida auris in all patients is not required in our hospital as the prevalence was very low and not cost-effective. Therefore we plan to modify our screening strategy and use risk factors based surveillance strategy as it may serve as an ideal strategy. [ABSTRACT FROM AUTHOR]

In the field of studies on the "Neural Synapses" in the nervous system, its experts manually (or pseudo-automatically) detect the bio-molecule clusters (e.g., of proteins) in many TIRF (Total Internal Reflection Fluorescence) images of a fluorescent cell and analyze their static/dynamic behaviors. This paper proposes a novel method for the automatic detection of the bio-molecule clusters in a TIRF image of a fluorescent cell and conducts several experiments on its performance, e.g., mAP @ IoU (mean Average Precision @ Intersection over Union) and F1-score @ IoU, as an objective/quantitative means of evaluation. As a result, the best of the proposed methods achieved 0.695 as its mAP @ IoU = 0.5 and 0.250 as its F1-score @ IoU = 0.5 and would have to be improved, especially with respect to its recall @ IoU. But, the proposed method could automatically detect bio-molecule clusters that are not only circular and not always uniform in size, and it can output various histograms and heatmaps for novel deeper analyses of the automatically detected bio-molecule clusters, while the particles detected by the Mosaic Particle Tracker 2D/3D, which is one of the most conventional methods for experts, can be only circular and uniform in size. In addition, this paper defines and validates a novel similarity of automatically detected bio-molecule clusters between fluorescent cells, i.e., SimMolCC, and also shows some examples of SimMolCC-based applications. [ABSTRACT FROM AUTHOR]

Abstract In vitro spermatogenesis (IVS) using air–liquid interphase organ culture method is possible with mouse testis tissues. The same method, however, has been hardly applicable to animals other than mice, only producing no or limited progression of spermatogenesis. In the present study, we challenged IVS of rats with modifications of culture medium, by supplementing chemical substances, including hormones, antioxidants, and lysophospholipids. In addition, reducing oxygen tension by placing tissues in an incubator of lower oxygen concentration and/or applying silicone cover ceiling on top of the tissue were effective for improving the spermatogenic efficiency. Through these modifications of the culture condition, rat spermatogenesis up to round spermatids was maintained over 70 days in the cultured tissue. Present results demonstrated a significant progress in rat IVS, revealing conditions commonly favorable for mice and rats as well as finding rat-specific optimizations. This is an important step towards successful IVS in many animal species, including humans.

Superficial siderosis (SS) of the central nervous system is a rare disease caused by chronic and repeated hemorrhages in the subarachnoid space. Recently, attention has been paid on the association of SS and dural defect with ventral fluid-filled collection in the spinal canal (VFCC). The pathophysiology of hemosiderin deposition in patients with SS and dural defects is still unclear. However, previous studies have suggested the possible mechanism: cerebrospinal fluid (CSF) leaks into the epidural space through the ventral dural defect, and repetitive bleeding occurs from the epidural vessels that circulate back to the subarachnoid space through the dural defect, leading to hemosiderin deposition on the surface of the brain, the central nerves, and the spinal cord. Previously, the surgical closure of dural defect via the posterior approach has been reported to be effective in arresting the continued subarachnoid bleeding and disease progression. Herein, we describe SS cases whose dural defects were repaired via the anterior approach. From the direct anterior approach to the ventral dural defect findings, we confirmed that the outer fibrous dura layer is intact, and the defect is localized in the inner thin layer. From the findings of this study, our proposed theory is that dural tear at the inner dural layer causes “dural dissection,” which is likely to occur between the outer fibrous layer and inner dural border cellular layer. Bleeding from the vessels between the inner and outer Line 39–40 dural layers seems to be the pathology of SS with dural defect.

The business world is changing due to the occupational climate and a large proportion of business executives that are bound to retire in the nearest future leading to an anticipated great loss of knowledge and performance. The paper seeks to evaluate job performance by considering the effect of mentoring on employee performance in the Nigerian service sector. Research focuses on finding out the level at which exposure, counseling, and role modelling affect employee performance in the Nigerian service sector.

Abstract Background At present, one out of six couples is infertile, and in 50% of cases, infertility is attributed to male infertility factors. Genetic abnormalities are found in 10%‐20% of patients showing severe spermatogenesis disorders, including non‐obstructive azoospermia. Methods Literatures covering the relationship between male infertility and genetic disorders or chromosomal abnormalities were studied and summarized. Main findings (Results) Genetic disorders, including Klinefelter syndrome, balanced reciprocal translocation, Robertsonian translocation, structural abnormalities in Y chromosome, XX male, azoospermic factor (AZF) deletions, and congenital bilateral absence of vas deferens were summarized and discussed from a practical point of view. Among them, understanding on AZF deletions significantly changed owing to advanced elucidation of their pathogenesis. Due to its technical progress, AZF deletion test can reveal their delicate variations and predict the condition of spermatogenesis. Thirty‐nine candidate genes possibly responsible for azoospermia have been identified in the last 10 years owing to the advances in genome sequencing technologies. Conclusion Genetic testing for chromosomes and AZF deletions should be examined in cases of severe oligozoospermia and azoospermia. Genetic counseling should be offered before and after genetic testing.

The study examined the impact of business innovation on competitive advantage in the Nigerian Manufacturing Sector. The study was anchored on the theory of the resource-based theory and the dynamic capabilities theory. The descriptive survey design was employed. The population for the study comprised 496 staff of Nestle Nigeria Plc, Ogun State. A sample size of 217 respondents was selected through stratified sampling and a simple random sampling procedure. The questionnaire was administered to the respondents, out of which 207 were retrieved and subjected to further analysis. The stated hypotheses were tested using ordinal regression. The results showed that business innovation has a significant effect on the cost of the product (R2=0.729, F=11.237; p

We previously reported a phenotype of Creutzfeldt-Jakob disease (CJD), CJD-MMiK, that could help identify iatrogenic CJD. To find cases mimicking CJD-MMiK, we investigated clinical features and pathology of 1,155 patients with diagnosed sporadic CJD or unclassified CJD with and without history of neurosurgery. Patients with history of neurosurgery more frequently had an absence of periodic sharp-wave complexes on electroencephalogram than patients without a history of neurosurgery. Among 27 patients with history of neurosurgery, 5 had no periodic sharp-wave complexes on electroencephalogram. We confirmed 1 case of CJD-MMiK and suspected another. Both had methionine homozygosity at codon 129 of the prion protein gene and hyperintensity lesions in the thalamus on magnetic resonance images of the brain, which might be a clinical marker of CJD-MMiK. A subgroup with a history of neurosurgery and clinical features mimicking dura mater graft-associated CJD might have been infected during neurosurgery and had symptoms develop after many years.

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011–2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.

Prion diseases are fatal, transmissible neurodegenerative disorders characterized by deposition of abnormal prion protein ([PrP.sup.Sc]) in the brain (1). Human prion diseases, which include Creutzfeldt-Jakob disease (CJD), are classified into [...]

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We investigated how the presence of the highly range-restricted Agulhas Long-billed Lark Certhilauda brevirostris (ALBL) varies with vegetation type and landscape features. The lark's distribution is nearly completely outside formally protected areas and overlaps with a region where agriculture has transformed the landscape, with very little of the original vegetation type remaining. Establishing important habitat requirements is needed to better manage conservation efforts for the species. We conducted 10-minute point counts at 51 sites along small rural roads quarterly between October 2020 and January 2022, and recorded ALBL in 58% of the counts. A subset of 45 sites was used to model occupancy. According to a null constant parameter model, occupancy at sample sites was high (0.91) with a detection probability of 0.67 for each site where the species was present. Modelling of habitat features and vegetation type found that ALBL occupancy was best explained by the presence of renosterveld, the shrubby indigenous vegetation type. Occupancy increased at a site up to 25% renosterveld cover, after which there was no effect. Occupancy was also positively associated with renosterveld vegetation presence along fence lines and a combination of renosterveld and decreasing riverine vegetation cover. Presence was little modified by seasonal changes in agricultural land use. Overall, our results suggest that although the ALBL is locally abundant, certain habitat features need to be preserved to ensure the species' continued presence in this agricultural region. [ABSTRACT FROM AUTHOR]

There is a growing need for a mouthguard sheet material with higher shock absorption and dispersion capacity than those obtained by conventional materials. A five-layer mouthguard sheet material was previously developed using laminated ethylene vinyl acetate and polyolefin copolymer resin. In this study, the shock absorption capacity and dispersion capability of the new sheet material were investigated and compared with those of other materials. Impact testing for the new sheet material showed that the force required to displace the sheet by 1 mm was significantly higher at all thicknesses (p<0.001), whereas the puncture energy and displacement were significantly lower than those for ethylene vinyl acetate (p<0.05). The five-layer mouthguard sheet material successfully absorbed and resisted shock. Therefore, the sheet material potentially increases resistance to applied deformation in teeth and alveolar bone and maintains structure. The five-layer sheet material could expand the range of mouthguard products and help prevent oral trauma. [ABSTRACT FROM AUTHOR]

In today’s dynamic and turbulent business environment, diversification has become a catalyst for achieving competitive advantages and the creation of synergy in market operations. This is because manufacturing companies operate in a highly competitive environment, especially among firmsthat produce the same or similar goods. This study examines the effect of a diversification strategy on an organization’s performance in the manufacturing sector. A quasi-experimental study with an ex-post facto research design were used for the study. The respondent populationconsists of thirty-one organizations listed in Nigerian Stock Exchange (NSE) for a period of 20 years (1997-2017), while the sample size is comprised of six organizations purposively selected based on their life-span and level of diversification. Three hypotheses were formulated and tested using ratio analysis, while performance was measured in terms of ROA, ROI and ROE; organization size, organizationvalue and growth; as well asleverage and liquidity. Data was drawn from the financial reports of the selected organizations, with E-View version 9 used for the data analysis. The study revealed that diversified organizations outperformundiversified ones in terms of ROA and ROI. While related diversified organizations were discovered to be positive in terms of ROA (26.8%), unrelated and hybrid diversified organizations were positive in ROE (81.7% and 20.5%). A diversification strategy leads to growth and profitability (20%) and a strong capital structure to cover liabilities (26%). The study concluded that diversification is a strategic tool for achieving strategic relevance and spontaneous performance.

Abstract Purpose Mouse in vitro spermatogenesis is possible with classical organ culture methods, by placing the testis tissue at the interphase between culture medium and air. In this condition, however, a tissue piece tends to round up to be compact, whose central region suffers from shortage of nutrients and oxygen. In this study, the authors improved the culture condition by spreading each tissue thin and flat, by which they were able to get better access to the oxygen and nutrients. Methods Immature mouse testis tissues placed on agarose gel block were forced to spread flat by covering with a polydimethylsiloxane (PDMS) ceiling chip (PC chip). They were then cultured for weeks and evaluated by the transgene expression of Acr‐Gfp, which reflects the progression of spermatogenesis. Results Testis tissues covered with PC chip initiated and maintained spermatogenesis in its wider region than those without PC chip covering. Flow cytometric analysis demonstrated that the PC method yielded more numerous meiotic germ cells than those without PC. Immunohistochemical examination confirmed the authentic histological figure of spermatogenesis from spermatogonia up to round or elongating spermatids. Conclusions The PC chip method is simple and effective to improve the efficiency of in vitro spermatogenesis in the organ culture system.

This study sought to examine the effect of organization structure on organization strategy. Survey research design was employed through the administration of structured questionnaire to staff of Nestle Nigeria PLC, Unilever Nigeria PLC and PZ (Cussons) PLC. The findings revealed that, organization structure positively and significantly affects strategy implementation (F stat 107.52* 0.000) and that organization structure account for 53% (Adjusted R2= 0.5312) variation in organization strategy. It can therefore be concluded that, organization structure plays a significant role in strategy formulation and implementation in Nigeria multinational enterprises. It could be seen that, global matrix structure and product division structure are the most critical elements of organization structure driving strategy implementation in a multinational firm. It is therefore recommended that, multinational firms in Nigeria should employ matrix structure towards the enhancement of their organization strategy. This is because matrix structure has the highest effect on organization strategy.

Takeshi Teshigawara,1–3 Akira Meguro,3 Sanae Sanjo,1 Seiichiro Hata,4 Nobuhisa Mizuki31Department of Ophthalmology, Yokosuka Chuoh Eye Clinic, Yokosuka, Kanagawa, Japan; 2Department of Ophthalmology, Tsurumi Chuoh Eye Clinic, Yokohama, Kanagawa, Japan; 3Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan; 4Department of Ophthalmology, Yokohama Sky Eye Clinic, Yokohama, Kanagawa, JapanAbstract: Zonulopathy is a major concern if found during cataract surgery as it can cause further complications. Such complications may occur during continuous curvilinear capsulorhexis (CCC), lens fragmentation and intraocular lens (IOL) implantation. Femtosecond laser-assisted cataract surgery (FLACS) devices, such as the LenSX (Alcon Laboratories) are advantageous because they can detect the area and largest point of zonulopathy via anterior segment optical coherent tomography (AS-OCT) before the manual part of the procedure. CCC and lens fragmentation can also minimize further zonular stress. A symmetrical CCC is ideal for IOL implantation in the sulcus with optic capture. In the present study, we did not detect significant zonular dehiscence preoperatively in either of the eyes of our 68-year-old patient when using AS-OCT (CASIA2 Tomey). However, LenSx AS-OCT revealed zonular dehiscence in both eyes, perioperatively. We created CCC and lens fragmentation without causing stress to the zonules. In the subsequent manual part of procedure, we found zonular dehiscence in the same area as indicated by LenSx AS-OCT, which extended to approximately 200° in the right eye and 180° in the left. After lens fragmentation by LenSx, we successfully removed the lens without further zonular dialysis. However, zonular dialysis (>180°) in the right eye was too large to insert an IOL, either in the capsule or the sulcus. Therefore, we performed scleral IOL implantation. In the left eye, we avoided using capsular tension ring (CTR) for IOL placement to avoid further iatrogenic damage to the zonule. Instead, an IOL was inserted into the sulcus with optic capture to reduce the possibility of further stress to the zonula and phimosis. Post-surgically, the patient regained good eyesight in both eyes. This case illustrates the advantages of FLACS in addressing zonulopathy. The consistent creation of CCC and lens fragmentation by FLACS may increase success rates, even in unexpectedly challenging cases.Keywords: femtosecond laser-assisted cataract surgery, phacodonesis, zonular dialysis, optic capture, anterior segment optical coherent tomography

Patients with advanced heart failure (HF) have reduced cardiac output and impaired peripheral blood flow, which diminishes endothelial shear stress and consequently flow-mediated dilatation (FMD). The aim of our study was to find out whether endothelial dysfunction is associated with the number of CD34+ cells and TNF-α levels in patients with ischemic and non-ischemic HF after stimulation with granulocyte colony-stimulating factor (G-CSF). We included 56 patients with advanced HF (LVEF < 35%). Eighteen patients (32.14%) had ischemic and 38 (67.86%) patients had non-ischemic HF. FMD of the brachial artery was performed before the patients underwent 5-day bone marrow stimulation with daily subcutaneous injections of G-CSF (5 μg/kg bid). On the fifth day peripheral blood CD34+ cell count was measured. No statistically significant differences were found between the patient groups in NT-proBNP levels ((1575 (425–2439) vs. 1273 (225–2239)) pg/mL; p = 0.40), peripheral blood CD34+ cell count ((67.54 ± 102.32 vs. 89.76 ± 71.21) × 106; p = 0.32), TNF-α ((8.72 ± 10.30 vs. 4.96 ± 6.16) ng/mL; p = 0.13) and FMD (6.7 ± 5.4 vs. 7.2 ± 5.9%; p = 0.76). In a linear regression model, only FMD (p = 0.001) and TNF-α (p = 0.003) emerged as statistically significant predictors of CD34+ cells counts. Our study suggests that TNF-α is a good predictor of impaired endothelial function and of CD34+ cells mobilization after G-CSF stimulation in patients with advanced HF of ischemic and non-ischemic origin.

Infections caused by Chromobacterium violaceum are extremely rare but can be relatively fatal in septicemia. We report a case of a 76 year old female who presented with pustules in the skin and later developed into septicemia. She succumbed to the illness despite escalating the antibiotic therapy to meropenem. To the best of our knowledge this is the 16th case report from India.

Climate change and climate variability are projected to alter the geographic suitability of lands for crop cultivation. Early awareness of the future climate of the current cultivation areas for a perennial tree crop like coconut is needed for its adaptation and sustainable cultivation in vulnerable areas. We analyzed coconut’s vulnerability to climate change in India, based on climate projections for the 2050s and the 2070s under two Representative Concentration Pathways (RCPs): 4.5 and 8.5. Based on the current cultivation regions and climate change predictions from seven ensembles of Global Circulation Models, we predict changes in relative climatic suitability for coconut cultivation using the MaxEnt model. Bioclimatic variables Bio 4 (temperature seasonality, 34.4%) and Bio 7 (temperature annual range, 28.7%) together contribute 63.1%, which along with Bio 15 (precipitation seasonality, 8.6%) determined 71.7% of the climate suitability for coconuts in India. The model projected that some current coconut cultivation producing areas will become unsuitable (plains of South interior Karnataka and Tamil Nadu) requiring crop change, while other areas will require adaptations in genotypic or agronomic management (east coast and the south interior plains), and yet in others, the climatic suitability for growing coconut will increase (west coast). The findings suggest the need for adaptation strategies so as to ensure sustainable cultivation of coconut at least in presently cultivated areas.

The study investigated the effect of service and process innovation on internationalization of Nigeria deposit money banks, using a survey research design. A structured questionnaire was administered to a purposively selected sample of seven hundred and sixty five (765) staff of five international banks; from the population of one thousand six hundred and fifteen (1615) staff of strategy and international operation departments of the ten Central Bank of Nigeria (CBN) licensed international banks. Ordinary Least Squares was employed to estimate the regression model and this was done with the aid of STATA 12. The findings revealed that service and process innovation significantly affect bank’s internationalization. It is therefore recommended that banks seeking internationalization should adopt services and processes innovativeness strategy.

Firms are adopting collaborative network, which allow group of enterprises to enhance their performance and competitiveness. This study examines the effect of business ecosystem on MSMEs financial and non financial performance. The study employed survey research design, through the administration of structured questionnaires to 400 chief executives of MSMEs in Lagos, Anambra and Kano. The research instrument was validated by some academics and practitioners. A pilot study was conducted to ascertain the reliability of the instrument, by distributing the questionnaire to chief executives of 10 MSMEs twice within an interval of 14 days and the correlation of the first and the second study gave a Cronbach alpha of 0.84, which indicated that the instrument is highly reliable. Hypotheses were formulated and ordinary least square was employed to estimate the model with the aid of STATA version 14. Findings revealed that business eco system have positive and significant effect on MSMEs financial and non-financial performance. Therefore, it is recommended that MSMEs should consider their business eco system towards the enhancement of their financial and non financial performance.