Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversity of fungal pathogens associated with loquat and development of novel virulence scales

Loquat [Eriobotrya japonica (Thunb.) Lindl. ] is an important fruit crop in Pakistan; however, a constant decline in its production is noted due biotic and abiotic stresses, particularly disease infestation. Fungal pathogens are the major disease-causing agents; therefore, their identification is necessary for devising management options. This study explored Taxila, Wah-Cantt, Tret, Chatar, Murree, Kalar-Kahar, Choa-Saidan-Shah and Khan-Pur districts in the Punjab and Khyber Paktoon Khawa (KPK) provinces of Pakistan to explore the diversity of fungal pathogens associated with loquat. The samples were collected from these districts and their microscopic characterizations were accomplished for reliable identification. Alternaria alternata, Curvularia lunata, Lasiodiplodia theobromae, Aspergilus flavis, Botrytis cinerea, Chaetomium globosum, Pestalotiopsis mangiferae and Phomopsis sp. were the fungal pathogens infesting loquat in the study area. The isolates of A. alternata and C. lunata were isolated from leaf spots and fruit rot, while the isolates of L. theobromae were associated with twig dieback. The remaining pathogens were allied with fruit rot. The nucleotide evidence of internal transcribed spacer (ITS) regions (ITS1, 5.8S, and ITS2) were computed from all the pathogens and submitted in the database of National Center for Biotechnology Information (NCBI). For multigene analysis, beta-tubulin (BT) gene and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) regions were explored for A. alternata and C. lunata isolates, respectively. The virulence scales of leaf spots, fruit rot, and twig dieback diseases of loquat were developed for the first time through this study. It is the first comprehensive study with morpho-molecular identification, and newly developed virulence scales of the fungal pathogens associated with loquat, which improves the understanding of these destructive diseases.
Embryogenic callus induction from immature zygotic embryos and genetic transformation of Larix kaempferi 3x Larix gmelinii 9

To date, there are few reports of the successful genetic transformation of larch and other conifers, mainly because it is difficult to transform and integrate exogenous genes. In this study, hybrid larch Larix kaempferi 3x Larix gmelinii 9 cones were collected on June 27, July 1, July 4, July 7 and July 16, 2017. Embryogenic callus induction was studied using a combination of different plant growth regulators and concentrations. The results showed that July 1 was the best stage; the highest induction rate was 10.83%, which cultured in BM medium (Button medium, which formula was listed in S1 Table) with 1.0 mg/L 2,4-D (2,4-dichlorophenoxyacetic acid) and 0.2 mg/L KT(kinetin). When cultured on a proliferation medium for 12 days, proliferation was the fastest, reaching 323.08%, which could also maintain the freshness and vitality. The suitable pre-culture medium for somatic embryogenesis was 1/4 BM medium containing 10 g/L inositol and 60 g/L sucrose. The combination of 45 mg/L ABA (abscisic acid) and 75 g/L PEG4000 (Polyethyene glycol 4000) could promote the number of somatic embryos, and reached the maximum, 210 140 per 1 g FW. The genetic transformation was carried out by the Agrobacterium-mediated transformation method with embryogenic callus cultured for 12 days. The results showed the optimal OD600 of the infection solution(suspension of A. tumefaciens) was 0.5, co-culture time was 2 days, and screening concentration of Hyg (hygromycin B) was 4 mg/L. In this study, the transformation rate of resistance callus was 32.1%. It provides a reference for low genetic transformation efficiency of larch at present. This study could be beneficial for the innovation and breeding of larch by genetic engineering and provides a certain basis for rapid propagation of excellent larch germplasm resources and genetic engineering breeding of larch and other conifers.
Trends in Demographics of Neurology House Staff in the United States

Background The lack of an adequate number of neurologists is a worldwide problem. As populations age, the prevalence of neurological disorders will likely increase, thereby increasing the demand for neurologists. In addition to the growing demand, inadequate diversity in the neurology healthcare workforce still exists. The purpose of this study is to examine the demographic characteristics of neurology residents and fellows. Methodology This cross-sectional study used data from the following publicly available databases: Accreditation Council for Graduate Medical Education, Association of American Medical Colleges, and the United States Census Bureau. Trends (from 2007 to 2018) in demographic characteristics were assessed using the slope and the associated p-value of a simple linear regression model, with the year as the independent variable. All p-values of <0.05 were considered significant. Results From 2007 through 2018, the percentage of US medical school graduates in neurology residency decreased from 58% to 55% (slope = -0.25; p = 0.0004), while the percentage of international medical graduates (IMGs) decreased from 36% to 32% (slope = -0.29; p = 0.0141) and doctor of osteopathy (DO) graduates increased from 6% to 13% (slope = 0.58; p < 0.0001). Although the percentage of female neurology residents increased from 39.5% in 2007 to 43.1% in 2018 (slope = 0.03; p = 0.8659), female physicians were underrepresented in vascular neurology fellowship (34% in 2018). Collectively, the percentage of underrepresented minorities in neurology residencies was low and increased only slightly over time (from 8% in 2011 to 9% in 2018; slope = 0.17; p = 0.0788). In 2018, the proportion of underrepresented minorities was smaller in neurology fellowships (5.5% neurophysiology, 12.5% epilepsy, 10.4% neuromuscular, and 12.4% vascular) compared to the population as a whole (31.3%). Conclusions IMGs still play an important role in filling a significant portion of the neurology residencies and fellowships. DO graduates have slowly increased in neurology residencies and fellowships. Members of several racial/ethnic minority groups and women are underrepresented in neurology house staff and efforts need to be taken to increase diversity.
Lung cancer screening: a critical appraisal

Purpose of review The recently published large-scale NELSON trial showed a reduction in lung cancer (LC) mortality with the use of low-dose computed tomography (LDCT) in high-risk patients. This is the first such European-based trial to mirror the results of the US National Lung Screening Trial (NLST). The NLST was responsible for nationwide implementation of LC screening protocols which has shown a decrease in LC mortality. However, the implementation of such screening in Europe has been challenging. With the findings from the NELSON trial, implementation of LC screening throughout Europe should once again be evaluated. Recent findings This review article further elaborates on the advantages of LDCT in LC screening. It also discusses promising future approaches that can supplement the current LC screening guidelines. Summary Implementation of LC screening with LDCT should again be evaluated throughout Europe as it could substantially decrease LC-related mortality.
An LMNA synonymous variant associated with severe dilated cardiomyopathy: Case report

Dilated cardiomyopathy (DCM) is one of the most common cardiac phenotypes caused by mutations of lamin A/C (LMNA) gene in humans. In our study, a cohort of 57 patients who underwent heart transplant for dilated cardiomyopathy was screened for variants in LMNA. We identified a synonymous variant c.936G>A in the last nucleotide of exon 5 of LMNA in a DCM family. Clinically, the LMNA variant carriers presented with severe familial DCM, conduction disease, and high creatine‐kinase level. The LMNA c.936G>A variant is novel and has not been reported in current genetic variant databases. Sanger sequencing results showed the presence of LMNA c.936G>A variant in the genomic DNA but not in the cDNA derived from one family member's heart tissue. Real‐time quantitative polymerase chain reaction showed significantly lower LMNA mRNA levels in the patient's heart compared to the controls, suggesting that the c.936G>A LMNA variant resulted in reduced mRNA and possibly lower protein expression of LMNA. These findings expand the understanding on the association between synonymous variant of LMNA and the molecular pathogenesis in DCM patients.
Post-Stroke Cognitive Impairment: Pathophysiological Insights into Brain Disconnectome from Advanced Neuroimaging Analysis Techniques

The neurological symptoms of stroke have traditionally provided the foundation for functional mapping of the brain. However, there are many unresolved aspects in our understanding of cerebral activity, especially regarding high-level cognitive functions. This review provides a comprehensive look at the pathophysiology of post-stroke cognitive impairment in light of recent findings from advanced imaging techniques. Combining network neuroscience and clinical neurology, our research focuses on how changes in brain networks correlate with post-stroke cognitive prognosis. More specifically, we first discuss the general consequences of stroke lesions due to damage of canonical resting-state large-scale networks or changes in the composition of the entire brain. We also review emerging methods, such as lesion-network mapping and gradient analysis, used to study the aforementioned events caused by stroke lesions. Lastly, we examine other patient vulnerabilities, such as superimposed amyloid pathology and blood-brain barrier leakage, which potentially lead to different outcomes for the brain network compositions even in the presence of similar stroke lesions. This knowledge will allow a better understanding of the pathophysiology of post-stroke cognitive impairment and provide a theoretical basis for the development of new treatments, such as neuromodulation.
Brain Networks Modulation in Young and Old Subjects During Transcranial Direct Current Stimulation Applied on Prefrontal and Parietal Cortex

Evidence indicates that the transcranial direct current stimulation (tDCS) has the potential to transiently modulate cognitive function, including age-related changes in brain performance. Only a small number of studies have explored the interaction between the stimulation sites on the scalp, task performance, and brain network connectivity within the frame of physiological aging. We aimed to evaluate the spread of brain activation in both young and older adults in response to anodal tDCS applied to two different scalp stimulation sites: Prefrontal cortex (PFC) and posterior parietal cortex (PPC). EEG data were recorded during tDCS stimulation and evaluated using the Small World (SW) index as a graph theory metric. Before and after tDCS, participants performed a behavioral task; a performance accuracy index was computed and correlated with the SW index. Results showed that the SW index increased during tDCS of the PPC compared to the PFC at higher EEG frequencies only in young participants. tDCS at the PPC site did not exert significant effects on the performance, while tDCS at the PFC site appeared to influence task reaction times in the same direction in both young and older participants. In conclusion, studies using tDCS to modulate functional connectivity and influence behavior can help identify suitable protocols for the aging brain.
Healthcare-associated foodborne outbreaks in high-income countries: a literature review and surveillance study, 16 OEDC countries, 2001 to 2019

Background Healthcare-associated foodborne outbreaks (HA-FBO) may have severe consequences, especially in vulnerable groups. Aim The aim was to describe the current state of HA-FBO and propose public health recommendations for prevention. Methods We searched PubMed, the Outbreak Database (Charité, University Medicine Berlin), and hand-searched reference lists for HA-FBO with outbreak onset between 2001 and 2018 from Organisation for Economic Co-operation and Development (OECD) countries and HA-FBO (2012–2018) from the German surveillance system. Additionally, data from the European Food Safety Authority were analysed. Results The literature search retrieved 57 HA-FBO from 16 OECD countries, primarily in the US (n = 11), Germany (n = 11) and the United Kingdom (n = 9). In addition, 28 HA-FBO were retrieved from the German surveillance system. Based on the number of outbreaks, the top three pathogens associated with the overall 85 HA-FBO were Salmonella (n = 24), norovirus (n = 22) and Listeria monocytogenes (n = 19). Based on the number of deaths, L. monocytogenes was the main pathogen causing HA-FBO. Frequently reported implicated foods were ‘mixed foods’ (n = 16), ‘vegetables and fruits’ (n = 15) and ‘meat and meat products’ (n = 10). Consumption of high-risk food by vulnerable patients, inadequate time-temperature control, insufficient kitchen hygiene and food hygiene and carriers of pathogens among food handlers were reported as reasons for HA-FBO. Conclusion To prevent HA-FBO, the supply of high-risk food to vulnerable people should be avoided. Well working outbreak surveillance facilitates early detection and requires close interdisciplinary collaboration and exchange of information between hospitals, food safety and public health authorities.
Tobacco Control Stakeholder Perspectives on the Future of Tobacco Marketing Regulation in Indonesia: A Modified Delphi Study

Objectives Tobacco control in Indonesia is very lenient compared to international standards. This study explored the perspectives of tobacco control stakeholders (TCSs) on the likelihood of advancing tobacco marketing regulation in Indonesia. Methods Data were collected from TCSs who were members of the Indonesia Tobacco Control Network group in a modified Delphi study. We collected the data in 2 waves using a questionnaire that comprised a set of closed and open-ended questions. For this paper, we analysed 2 of the 3 sections of the questionnaire: (1) tobacco advertising, promotions, and sponsorship (TAPS) bans, and (2) marketing and retailing regulations. We conducted a descriptive analysis of the scores using Stata/IC.13 and summarised the comments for each item. Results The TCSs viewed the measures/strategies across all aspects of TAPS and tobacco marketing regulation as highly desirable, but provided varied responses on their feasibility. They rated political feasibility lower than technical feasibility for most measures. Advancing TAPS measures and prohibition of selling to minors were considered more attainable by sub-national governments, while prohibition of tobacco corporate social responsibility was considered as the least feasible measure in the next 5 years. Conclusions Despite little optimism for substantial national-level change, there is a positive expectation that sub-national governments will strengthen their tobacco control regulation. It is paramount that the government reduce tobacco industry leverage by implementing Article 5.3 of the World Health Organization Framework Convention on Tobacco Control. Extending advocacy networks beyond tobacco control groups and framing tobacco control more effectively are necessary steps.
The gist of it: offloading memory does not reduce the benefit of list categorisation

ABSTRACT When we can offload to-be-remembered information to an external store, our ability to recall that information from internal memory can be diminished. However, previous research has suggested that associative memory processes may remain intact in the face of offloading behaviour. In the present investigation, we examine how the opportunity to offload memory demands affects the learning of categorised word lists. Across six experiments, participants studied and wrote down word lists that were either strongly associated with a semantic theme (categorised) or word lists that consisted of the same set of words but shuffled across the categorised lists (shuffled). When participants expected to have access to their written lists during the recall test (i.e., a condition that would encourage offloading) but were not given access to it, we found the typical recall advantage for categorised lists. This effect was found to be the same size or larger compared to a condition where participants did not expect to have access to their written lists during the recall test (i.e., a condition that would not allow offloading). We propose that gist memory supported by semantic associations is not substantially reduced in offloading.
Simulating the Selection of Resistant Cells with Bystander Killing and Antibody Coadministration in Heterogeneous Human Epidermal Growth Factor Receptor 2–Positive Tumors

Intratumoral heterogeneity is a leading cause of treatment failure resulting in tumor recurrence. For the antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1), two major types of resistance include changes in human epidermal growth factor receptor 2 (HER2) expression and reduced payload sensitivity, which is often exacerbated by heterogenous HER2 expression and ADC distribution during treatment. ADCs with bystander payloads, such as trastuzumab-monomethyl auristatin E (T-MMAE), can reach and kill adjacent cells with lower receptor expression that cannot be targeted directly with the ADC. Additionally, coadministration of T-DM1 with its unconjugated antibody, trastuzumab, can improve distribution and minimize heterogeneous delivery. However, the effectiveness of trastuzumab coadministration and ADC bystander killing in heterogenous tumors in reducing the selection of resistant cells is not well understood. Here, we use an agent-based model to predict outcomes with these different regimens. The simulations demonstrate that both T-DM1 and T-MMAE benefit from trastuzumab coadministration for tumors with high average receptor expression (up to 70% and 40% decrease in average tumor volume, respectively), with greater benefit for nonbystander payloads. However, the benefit decreases as receptor expression is reduced, reversing at low concentrations (up to 360% and 430% increase in average tumor volume for T-DM1 and T-MMAE, respectively) for this mechanism that impacts both ADC distribution and efficacy. For tumors with intrinsic payload resistance, coadministration uniformly exhibits better efficacy than ADC monotherapy (50%–70% and 19%–36% decrease in average tumor volume for T-DM1 and T-MMAE, respectively). Finally, we demonstrate that several regimens select for resistant cells at clinical tolerable doses, which highlights the need to pursue other mechanisms of action for durable treatment responses. SIGNIFICANCE STATEMENT Experimental evidence demonstrates heterogeneity in the distribution of both the antibody-drug conjugate and the target receptor in the tumor microenvironment, which can promote the selection of resistant cells and lead to recurrence. This study quantifies the impact of increasing the antibody dose and utilizing bystander payloads in heterogeneous tumors. Alternative cell-killing mechanisms are needed to avoid enriching resistant cell populations.
The association between dietary patterns and the novel inflammatory markers platelet-activating factor and lipoprotein-associated phospholipase A2: a systematic review

Abstract Context Atherosclerosis is a disease of chronic inflammation. Recent research has identified 2 novel inflammatory biomarkers: platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Diet has been proposed as a mediator of inflammation, but to date, the focus for these novel biomarkers has been on individual foods and nutrients rather than overall dietary patterns. Objective To systematically review the literature on the association between dietary patterns and PAF and Lp-PLA2. Data Sources The PubMed, Embase, CINAHL, and Cochrane CENTRAL literature databases were searched. Data Analysis Study quality was evaluated using the Quality Criteria Checklist. Sixteen studies (n = 4 observational and n = 12 interventional) were included and assessed for associations between dietary patterns and PAF and Lp-PLA2. Conclusion Study quality varied from neutral (n = 10) to positive (n = 6). Mediterranean, heart healthy, and vegetarian dietary patterns were associated with improved levels of PAF and Lp-PLA2. Conversely, Western dietary patterns were less favorable. A range of well-established, healthier dietary patterns may lower inflammation and the risk of atherosclerosis. More well-designed studies are needed to confirm these findings and identify other dietary patterns that improve inflammation.
Bayesian inference and dynamic prediction of multivariate joint model with functional data: An application to Alzheimer's disease

Alzheimer's disease (AD) is a severe neurodegenerative disorder impairing multiple domains, for example, cognition and behavior. Assessing the risk of AD progression and initiating timely interventions at early stages are critical to improve the quality of life for AD patients. Due to the heterogeneous nature and complex mechanisms of AD, one single longitudinal outcome is insufficient to assess AD severity and disease progression. Therefore, AD studies collect multiple longitudinal outcomes, including cognitive and behavioral measurements, as well as structural brain images such as magnetic resonance imaging (MRI). How to utilize the multivariate longitudinal outcomes and MRI data to make efficient statistical inference and prediction is an open question. In this article, we propose a multivariate joint model with functional data (MJM‐FD) framework that relates multiple correlated longitudinal outcomes to a survival outcome, and use the scalar‐on‐function regression method to include voxel‐based whole‐brain MRI data as functional predictors in both longitudinal and survival models. We adopt a Bayesian paradigm to make statistical inference and develop a dynamic prediction framework to predict an individual's future longitudinal outcomes and risk of a survival event. We validate the MJM‐FD framework through extensive simulation studies and apply it to the motivating Alzheimer's Disease Neuroimaging Initiative (ADNI) study.
An analysis of the heart rates and the therapeutic effect of aminophylline injections in patients with acute cervical spinal cord injuries and bradycardia.

OBJECTIVE To investigate the changes in the heart rates and the clinical effectiveness of aminophylline injections in acute cervical spinal cord injury (ACSCI) patients with bradycardia. METHODS This retrospective study was conducted by studying the clinical data of 100 ACSCI patients also suffering from bradycardia admitted to our hospital from June 2019 to June 2020. The patients were randomly placed into a control group (n=50) that was administered atropine therapy and a test group (n=50) that was administered aminophylline injections. The changes in the patients' heart rates and the clinical effectiveness were analyzed. RESULTS After the treatment, the test group had a significantly higher average heart rate, shorter heart rate recovery times, and a lower bradycardia recurrence rate than the control group (all P<0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in the test group were significantly higher than they were in the control group (all P<0.05). Remarkably higher clinical effectiveness and satisfaction rates and a significantly lower incidence of adverse reactions were observed in the test group compared to the control group (all P<0.05). In addition, the Japanese Orthopaedic Association (JOA) cervical spine scores were similar in the two groups (P>0.05). CONCLUSION For ACSCI patients also suffering from bradycardia, aminophylline injections ameliorate the clinical heart rate and have a good clinical effectiveness with few adverse reactions, so the treatment merits clinical promotion and application.