Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing the quality of the evidence underlying recommendations in type 2 diabetes' commonly used clinical practice guidelines.

AIM In a world of data overload, clinical practice recommendations are needed to help practitioners and patients to take evidence-based decisions. However, in the field of type 2 diabetes mellitus (T2DM) recommendations on glycemic goals and treatment choice are controversial in spite of being supported by a common body of evidence. We hypothesize that internal and external validity of this body of evidence might not be as sound as expected. The aim of the current study is to appraise the studies supporting recommendations developed by influential medical societies dealing with glycemic goals and the choice of pharmacological treatment in adults with T2DM. METHODS Clinical practice recommendations and their references were extracted out of eight documents developed by influential scientific societies between 2016 and 2019. Internal and external validity of each study was then appraised with standard tools and in duplicate. RESULTS A total of 114 recommendations and their underlying 233 citations were extracted. Out of these 233 citations 81 (35%) corresponded to randomized controlled trials (RCT) and 45 (20%) to systematic reviews. After systematical appraisal only four RCT (5%) and eight systematic reviews (17%) were considered to be unflawed. Indirectness (lack of generalizability) was the most common caveat identified in RCTs. Out of the 114 recommendations analyzed (32 dealing with glycemic goals and 82 with treatment choice), only 21 (18.4%) were supported by at least one high-quality study. CONCLUSION Only one in five recommendations regarding glycemic goals or pharmacological treatment choice in T2DM is based on at least one high-quality study. Clinical practice recommendations dealing with areas of uncertainty should be formulated more transparently to enable real evidence-based decisions.
Demyelination in Leprosy

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that has a predilection for peripheral nerves, especially Schwann cells (SCs). Leprosy medications may only eradicate the bacteria without preventing or recovering peripheral nerve damage. Early nerve damage detection is necessary. The expression of Krox-20 in Schwann cells will be examined immunohistochemically, and the level of neuron growth factor (NGF), neuregulin 1 (NRG1), protein 0 (P0), and peripheral myelin protein 22 (PMP22) will be examined in the blood plasmas. A significant decrease was noticed in Krox-20 and NGF, NRG1, P0, and PMP22 level (p < 0.05) in disability degree 1 compared to degree 0. Studies proved that markers have shown promising results; Krox-20, NGF, NRG1, P0, and PMP22 could be useful diagnostic tools for early peripheral nerve damage detection in leprosy. levels of NF protein content in the infected nerve. These results indicate the presence of hypo-phosphorylated NF subunits during leprosy infection, which are thought to lead to increasing susceptibility to proteolytic degradation of NFS. This result is consistent with the previous research, where phosphorylation was found to protect NFS against nonspecific proteolysis by calpain. Several studies by Shetty et al. found that lipoarabinomannan (LAM) M. leprae could inhibit the protein kinase C (PKC) enzyme which is responsible for the phosphorylation of the neurofilament protein. Recently, Save et al. also found that hypophosphorylation of NFS proteins by measuring the activity of enzyme kinases is responsible for NFS phosphorylation in the nerves of infected mice. The authors point out that as long as NFS loses its reactivity to specific NF-phosphate (SMI 31) antibodies, there is a decrease in KSPXK kinase activity from cyclin-dependent kinase (CDK) and MAPK in M. leprae -infected nerves. Decreases in NFS phosphorylation and NFS degradation may subsequently result in decreasing in interfilamen tary distances that affect axonal growth and result in axonal atrophy.
Lumbar Facet Tropism on Different Facet Portions and Asymmetry between Ipsilateral Cephalad and Caudad Portions: Their Correlations with L4/5 and L5/S1 Lumbar Disc Herniation.

STUDY DESIGN A retrospective case-control study. OBJECTIVE To investigate the correlation between lumbar disc herniation (LDH) and lumbar facet tropism (FT) on cephalad and caudad facet portions, respectively; to investigate the asymmetry between ipsilateral cephalad and caudad facet portions and its correlation with LDH. SUMMARY OF BACKGROUND DATA There are still heavy debates on the exact correlation between lumbar FT and LDH. However, no study ever focused on the FT on different facet portions and asymmetry between ipsilateral cephalad and caudad portions in patients with LDH. METHODS One hundred patients with L4/5 LDH, 100 patients with L5/S1 LDH and 100 participants without LDH (control group) were age and gender matched and included in this study. Participants in each group were further divided into two subgroups based on age (≥ or < 50 years old). Bilateral facet joint angles on both cephalad and caudad portions were measured. FT and asymmetry between ipsilateral cephalad and caudad portions in each LDH group were compared with those in corresponding control group. RESULTS Comparing with control participants, the mean difference of bilateral facet angles in older patients with L4/5 LDH was significantly greater either on cephalad portion and caudad portion, whereas significantly higher frequency of FT was only exhibited on cephalad portion. In older patients with L4/5 LDH, the mean difference of facet angle between ipsilateral cephalad and caudad portions was significantly greater than that of control participants, the frequency of ipsilateral cephalad and caudad facet asymmetry was also significantly higher. CONCLUSIONS Only the FT on cephalad portion but not caudad portion of facet joint is associated with L4/5 LDH of older patients. The measurement on different portions of facet joint may result in discrepancy on FT identification. Asymmetry between ipsilateral cephalad and caudad facet portions is also associated with L4/5 LDH in older patients. LEVEL OF EVIDENCE 3.
The role of electrodiagnostic testing in patients referred with the suspicion of polyneuropathy

We have read with great interest the article by Ginsberg and Morren and the accompanying editorial. The authors performed a retrospective chart review of patients referred for electrodiagnostic (EDx) evaluation of peripheral polyneuropathy (PNP). Of the 162 patients analyzed, 32.1% had PNP, whereas the others had alternative diagnoses without PNP (31.5%), or normal studies (36.4%). Interestingly, the number of patients with normal nerve conduction studies (NCS) was higher than the number of patients with PNP. We suspect referral sources as themain reason for such a low number of patientswith confirmed PNP. In another recent study,we prospectively recruited 313 consecutive patients referred by neurologists for suspicion of PNP. As the diagnostic reference standardwe used the final clinical diagnosis from patients' medical records 1 to 6 years after their EDx evaluation. In our cohort, the proportion of patients with PNP (219 patients, 70%) was more than double that of Ginsberg and Morren's cohort. Of these, NCS confirmed the PNP diagnosis in 175 patients (56%of thewhole cohort).
Antiparasitic Activity of Bromotyrosine Alkaloids and New Analogues Isolated from the Fijian Marine Sponge Aplysinella rhax

Ten bromotyrosine alkaloids were isolated and characterised from the marine sponge Aplysinella rhax (de Laubenfels 1954) collected from the Fiji Islands, which included one new bromotyrosine analogue, psammaplin P and two other analogues, psammaplin O and 3‐bromo‐2‐hydroxy‐5‐(methoxycarbonyl)benzoic acid, which have not been previously reported from natural sources. HR‐ESI‐MS, 1D and 2D NMR spectroscopic methods were used in the elucidation of the compounds. Bisaprasin, a biphenylic dimer of psammaplin A, showed moderate activity with IC50 at 19±5 and 29±6 μM against Trypanzoma cruzi Tulahuen C4, and the lethal human malaria species Plasmodium falciparum clone 3D7, respectively, while psammaplins A and D exhibited low activity against both parasites. This is the first report of the antimalarial and antitrypanosomal activity of the psammaplin‐type compounds. Additionally, the biosynthesis hypotheses of three natural products were proposed.
The spatio-temporal biosynthesis of floral flavonols is controlled by differential phylogenetic MYB regulators in Freesia hybrida.

Floral flavonols play specific pivotal roles in pollinator attraction, pollen germination and fertility besides other functions in vegetative organs. In contrast to early flower developmental stages, flavonol biosynthesis in late flower developmental stages or matured flower tissues remains unclear in many plants, which might be regulated independent of subgroup 7 R2R3 MYB (SG7 MYB) transcription factors. In this study, two FLS genes were shown to be expressed synchronously with the flower development- and tissue- specific biosynthesis of flavonols in Freesia hybrida. FhFLS1 contributed to the flavonol biosynthesis in early flower buds and toruses or calyxes, and was regulated by four well-known SG7 MYB proteins, designated as FhMYBFs, with at least partial regulatory redundancy. FhFLS2 accounted for flavonols in late developed flowers and petal, stamen and pistil, and was targeted directly by non SG7 MYB protein FhMYB21L2. In parallel, AtMYB21 and AtMYB24 also activated AtFLS1, a gene highly expressed in Arabidopsis anther and pollen, indicating the conserved regulatory roles of MYB21 against FLS genes in these two evolutionarily divergent angiosperm plants. Our results reveal a novel regulatory and synthetic mechanism underlying flavonol biosynthesis in floral organs or tissues, and may be exploited to investigate supplementary roles of flavonols in flowers.
Cytokine storm syndrome in coronavirus disease 2019: A narrative review

Cytokine storm syndrome (CSS) is a critical clinical condition induced by a cascade of cytokine activation, characterized by overwhelming systemic inflammation, hyperferritinaemia, haemodynamic instability and multiple organ failure (MOF). At the end of 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China, and rapidly developed into a global pandemic. More and more evidence shows that there is a dramatic increase of inflammatory cytokines in patients with COVID‐19, suggesting the existence of cytokine storm in some critical illness patients. Here, we summarize the pathogenesis, clinical manifestation of CSS, and highlight the current understanding about the recognition and potential therapeutic options of CSS in COVID‐19.
A Change in the Structure of Vβ Chromatin Associated with TCR β Allelic Exclusion1

To investigate chromatin control of TCR β rearrangement and allelic exclusion, we analyzed TCR β chromatin structure in double negative (DN) thymocytes, which are permissive for TCR β recombination, and in double positive (DP) thymocytes, which are postallelic exclusion and nonpermissive for Vβ to DβJβ recombination. Histone acetylation mapping and DNase I sensitivity studies indicate Vβ and DβJβ segments to be hyperacetylated and accessible in DN thymocytes. However, they are separated from each other by hypoacetylated and inaccessible trypsinogen chromatin. The transition from DN to DP is accompanied by selective down-regulation of Vβ acetylation and accessibility. The level of DP acetylation and accessibility is minimal for five of six Vβ segments studied but remains substantial for one. Hence, the observed changes in Vβ chromatin structure appear sufficient to account for allelic exclusion of many Vβ segments. They may contribute to, but not by themselves fully account for, allelic exclusion of others.
Symptoms and predictors of depression among university students in the Kilimanjaro region of Tanzania: a cross-sectional study

Abstract Background Depression is the second leading cause of death among young people worldwide, and severity and suicidality are useful predictors of an adverse outcome. Aim This study aimed at examining factors associated with depression among university students in Tanzania. Methods A cross-sectional study was conducted between March 2018 and July 2019 of undergraduate students across four universities. They completed a self-reported questionnaire collecting socio-demographic, together with a Patient Health Questionnaire (PHQ-9) to screen for depression. A multivariate logistic regression model was used to determine independent predictors of depression. Results A total of 1047 students completed the study. Their mean (±SD) age was 24.2 (±7) years. 219 students (21.3%) screened positive for probable depression (survey-1 34% vs survey-2 13%). A total of 228 (21.9%) students reported having thoughts of serious self-harm. Factors independently influencing depression included year of study, substance abuse, unhappy interpersonal relationships and chronic mental or physical illness. The presence of an eating disorder was a predictor of depression and was recorded in 7.4% of all students. Conclusion Significant probable depression is present in one fifth of undergraduate students in this study. These results demonstrate a worrying degree of self- reported features of depression among North Tanzanian university students.
Isolated with persistence or dynamically connected? Genetic patterns in a common granite outcrop endemic

Granite outcrops are prominent throughout the world and harbour many endemic species. Their topographic complexity and range of environments have led to the hypothesis that they act as refugia facilitating the persistence of species through climate change. We evaluate this hypothesis by investigating the phylogeographic patterns in a common granite endemic shrub.
Long-Term Changes in Fish Assemblage Structure in the Yellow River Estuary Ecosystem, China

Abstract The Yellow River estuary ecosystem is an important spawning ground for many species found in the Bohai Sea and Yellow Sea and contributes substantially to the fishery resource structure and biological reproduction in the northern China Sea. Based on long-term ecosystem surveys in the Yellow River estuary during the main spawning period (May) of most fishery species from 1959 to 2011, the responses of the ecosystem, including regime shifts in species composition, biomass, diversity, and other related factors, were analyzed in this study. Since the 1980s, the dominant large-size species of high economic value (e.g., Largehead Hairtail Trichiurus lepturus) have been replaced by short-lived, low-trophic-level, planktivorous pelagic species (e.g., Scaly Hairfin Anchovy Setipinna taty and Japanese Anchovy Engraulis japonicus). Currently, traditional commercially targeted fishes, such as the Largehead Hairtail, Red Seabream Pagrus major, and Pacific Herring Clupea pallasii, are locally extinct. There has been a rapid shift of dominant species from highly valued, high-trophic-level, large-sized demersal species with complicated age structures to low-value, low-trophic-level, small-sized pelagic species with simple age structures; this shift has resulted in major changes to the ecological cycle and restoration of fishery resources. The fish catch declined from 421.66 kg/h in 1959 to 0.25 kg/h in 2008 and then increased to 3.62 kg/h in 2011. Diversity and evenness indices showed a continuously increasing trend during 1959–2011. The Yellow River estuary may be significantly compromised by overfishing, climate change, dam construction, and pollution, resulting in the decline of traditional fishing industries and reduced biodiversity in this ecosystem.
Report of foliar necrosis of potato caused by Cochliobolus lunatus in India

During the winter season of 2011, Cochliobolus lunatus was isolated from necrotized leaves of potato in potato plantations of Burdwan District, West Bengal State, India. The isolate was identified using standard monographs and taxonomic keys and confirmed molecularly using the Ribosomal Deoxyribonucleic acid (rDNA) sequence data. The Koch’s postulate was confirmed through pathogenicity test on potato cultivar ‘Kufri Jyoti’. This is the first report of C. lunatus causing brown-toblack spots disease of potato in India.
Chemical Composition and Antioxidant Activities of the Essential Oils of Different Parts of Cupressus arizonica Greene

Abstract The essential oils of different parts of Cupressus arizonica were examined for their potential radical scavenging activity. Fresh leaves and fruits of C. arizonica were steam distilled and the oils were analyzed qualitatively and quantitatively by GC and GC/MS. Different methods of rapid TLC screening, DPPH assay, desoxyribose assay, assay for site-specific reaction and non-enzymatic lipid peroxidation were employed to evaluate possible antioxidant activity of the oils and their main components, as well as the positive controls. The main components of these essential oils were α-pinene, cymene, myrcene, limonene, sabinene hydrate, cedrane and germacrene D. In rapid TLC screening, the tested compounds mainly showed antioxidant activity. In DPPH assay the stronger antioxidant effects were shown by the fruit oil of C. arizonia. In deoxyribose degradation assay test, most of the tested compounds showed some antioxidant effects. In non-enzymatic lipid peroxidation test, most antioxidant activity was shown by the fruit oil.
Common HTR2A variants and 5‐HTTLPR are not associated with human in vivo serotonin 2A receptor levels

The serotonin 2A receptor (5‐HT2AR) is implicated in the pathophysiology and treatment of various psychiatric disorders. [18F]altanserin and [11C]Cimbi‐36 positron emission tomography (PET) allow for high‐resolution imaging of 5‐HT2AR in the living human brain. Cerebral 5‐HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that HTR2A single nucleotide polymorphisms including rs6311/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5‐HT2AR or other serotonin (5‐HT) proteins, their effect on human in vivo brain 5‐HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5‐HTTLPR predict neocortex in vivo 5‐HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [18F]altanserin or [11C]Cimbi‐36 PET. Although we observed genotype group differences in 5‐HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5‐HT2AR binding in what is the largest human in vivo 5‐HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5‐HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5‐HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5‐HT2AR binding.
An NMR-based approach reveals the core structure of the functional domain of SINEUP lncRNAs

Abstract Long non-coding RNAs (lncRNAs) are attracting widespread attention for their emerging regulatory, transcriptional, epigenetic, structural and various other functions. Comprehensive transcriptome analysis has revealed that retrotransposon elements (REs) are transcribed and enriched in lncRNA sequences. However, the functions of lncRNAs and the molecular roles of the embedded REs are largely unknown. The secondary and tertiary structures of lncRNAs and their embedded REs are likely to have essential functional roles, but experimental determination and reliable computational prediction of large RNA structures have been extremely challenging. We report here the nuclear magnetic resonance (NMR)-based secondary structure determination of the 167-nt inverted short interspersed nuclear element (SINE) B2, which is embedded in antisense Uchl1 lncRNA and upregulates the translation of sense Uchl1 mRNAs. By using NMR ‘fingerprints’ as a sensitive probe in the domain survey, we successfully divided the full-length inverted SINE B2 into minimal units made of two discrete structured domains and one dynamic domain without altering their original structures after careful boundary adjustments. This approach allowed us to identify a structured domain in nucleotides 31–119 of the inverted SINE B2. This approach will be applicable to determining the structures of other regulatory lncRNAs.
Adaptation to a low carbohydrate high fat diet is rapid but impairs endurance exercise metabolism and performance despite enhanced glycogen availability

Brief (5–6 days) adaptation to a low carbohydrate high fat diet in elite athletes increased exercise fat oxidation to rates previously observed with medium (3–4 weeks) or chronic (>12 months) adherence to this diet, with metabolic changes being washed out in a similar time frame. Increased fat utilisation during exercise was associated with a 5–8% increase in oxygen cost at speeds related to Olympic Programme races. Acute restoration of endogenous carbohydrate (CHO) availability (24 h high CHO diet, pre‐race CHO) only partially restored substrate utilisation during a race warm‐up. Fat oxidation continued to be elevated above baseline values although it was lower than achieved by 5–6 days’ keto adaptation; CHO oxidation only reached 61% and 78% of values previously seen at exercise intensities related to race events. Acute restoration of CHO availability failed to overturn the impairment of high‐intensity endurance performance previously associated with low carbohydrate high fat adaptation, potentially due to the blunted capacity for CHO oxidation.
Current Trends and Future Approaches in Small-Molecule Therapeutics for COVID-19.

The novel coronavirus (SARS-CoV-2) pandemic has created a global public health emergency. The pandemic is causing substantial morbidity, mortality and significant economic loss. Currently, no approved treatments for COVID-19 are available, and it is likely to take at least 12-18 months to develop a new vaccine. Therefore, there is an urgent need to find new therapeutics that can be progressed to clinical development as soon as possible. Repurposing regulatory agencyapproved drugs and experimental drugs with known safety profiles can provide important repositories of compounds that can be fast-tracked to clinical development. Globally, over 500 clinical trials involving repurposed drugs have been registered, and over 150 have been initiated, including some backed by the World Health Organisation (WHO). This review is intended as a guide to research into small-molecule therapies to treat COVID-19; it discusses the SARS-CoV-2 infection cycle and identifies promising viral therapeutic targets, reports on a number of promising pre-approved small-molecule drugs with reference to over 150 clinical trials worldwide, and offers a perspective on the future of the field.
Adaptive NN Distributed Control for Time-Varying Networks of Nonlinear Agents With Antagonistic Interactions

This article proposes an adaptive neural network (NN) distributed control algorithm for a group of high-order nonlinear agents with nonidentical unknown control directions (UCDs) under signed time-varying topologies. An important lemma on the convergence property is first established for agents with antagonistic time-varying interactions, and then by using Nussbaum-type functions, a new class of NN distributed control algorithms is proposed. If the signed time-varying topologies are cut-balanced and uniformly in time structurally balanced, then convergence is achieved for a group of nonlinear agents. Moreover, the proposed algorithms are adopted to achieve the bipartite consensus of high-order nonlinear agents with nonidentical UCDs under signed graphs, which are uniformly quasi-strongly $\delta $ -connected. Finally, simulation examples are given to illustrate the effectiveness of the NN distributed control algorithms.