Miracle-dz/UniFAR-FTUs huggingface dataset:
Practice of Epidemiology Measurement of Vaccine Direct Effects Under the Test-Negative Design

Test-negative designs are commonplace in assessments of influenza vaccination effectiveness, estimating this value from the exposure odds ratio of vaccination among individuals treated for acute respiratory illness who test positive for influenza virus infection. This approach is widely believed to recover the vaccine direct effect by correcting for differential health-care-seeking behavior among vaccinated and unvaccinated persons. However, the relationship of themeasured odds ratio to true vaccine effectiveness is poorly understood. We derived the odds ratio under circumstances of realworld test-negative studies. The odds ratio recovers the vaccine direct effect when 2 conditions are met: 1) Individuals’ vaccination decisions are uncorrelated with exposure or susceptibility to the test-positive or test-negative conditions, and 2) vaccination confers “all-or-nothing” protection (whereby certain individuals have no protection while others are perfectly protected). Biased effect-size estimates arise if either condition is unmet. Such bias might suggest misleading associations of vaccine effectiveness with time since vaccination or the force of infection of influenza. The test-negative design could also fail to correct for differential health-care-seeking behavior among vaccinated and unvaccinated persons without stringent criteria for enrollment and testing. Our findings demonstrate a need to reassess how data from test-negative studies can inform policy decisions.
Methionine deficiency decreases hepatic lipid exportation and induces liver lipid accumulation in broilers

Abstract The objective of the study was to investigate the effects of deficiency or high level addition of methionine (Met) in diet on homocysteine (Hcy) metabolism and hepatic lipid metabolism in broiler. A completely random design was used with 3 dietary treatments with the addition of Met from DL‐methionine (DLM) at 0%, 0.22%, and 0.32% in a basal diet. The analyzed dietary Met was 0.271%, 0.485%, and 0.584% respectively for the Met‐deficient, sufficient, and excessive diet. A total of 360 one‐day‐old male Ross 308 broiler chicks were randomly assigned to the treatments. The trial was last for 21 d. Compared to the Met‐sufficient diet, the Met‐deficient diet significantly resulted the decrease of 1 to 21 d growth performance and the increase of liver ether extract (EE). Compared to the Met‐sufficient group, the expression of lipid transport gene apolipoprotein B (APOB) in both Met‐deficient and Met‐excessive group was decreased (P < 0.05). However, compared to the Met‐sufficient group, a decreased of serum low‐density lipoprotein cholesterol (LDLC) was only shown in birds fed a Met‐deficient diet (P < 0.05). Although the plasma Hcy content was decreased, the expression of Cystathionine &bgr;‐synthase (C&bgr;S) and hepatic inflammatory cytokines included interleukin‐1 (IL‐1) and interleukin‐8 (IL‐8) was significantly decreased in birds fed the Met‐deficient diet when compared to those in Met‐sufficient group (P < 0.05). When compared to the Met‐sufficient group, the broilers in high dietary Met group had increased levels of catabolic enzyme genes expression especially acyl‐coenzyme A oxidase 1 (ACOX1) and carbohydrate response element‐binding protein (CHREBP) (P < 0.05), and a decreased content of liver EE. In conclusion, dietary Met deficiency decreased the hepatic lipid export and subsequently increased the hepatic lipid accumulation. High dietary Met addition increased the hepatic lipid catabolism and subsequently decreased the liver lipid accumulation.
PDZD8 is not the ‘functional ortholog’ of Mmm1, it is a paralog

Authors of a recent paper demonstrate that, like ERMES (ER-mitochondria encounter structure) in fungal cells, PDZD8 (PDZ domain containing 8) tethers mitochondria to the ER in mammalian cells. However, identifying PDZD8 as a “functional ortholog” of yeast Mmm1 (maintenance of mitochondrial morphology protein 1) is at odds with the phylogenetic data. PDZD8 and Mmm1 are paralogs, not orthologs, which affects the interpretation of the data with respect to the evolution of ER-mitochondria tethering. Our phylogenetic analyses show that PDZD8 co-occurs with ERMES components in lineages closely related to animals solidifying its identity as a paralog of Mmm1. Additionally, we identify two related paralogs, one specific to flagellated fungi, and one present only in unicellular relatives of animals. These results point to a complex evolutionary history of ER-mitochondria tethering involving multiple gene gains and losses in the lineage leading to animals and fungi.
Elevated Levels of Intelectin-1, a Pathogen-binding Lectin, in the BAL Fluid of Patients with Chronic Eosinophilic Pneumonia and Hypersensitivity Pneumonitis

Objective Human intelectin-1 (hITLN-1) binds to galactofuranosyl residues, which are present in the microbial cell wall, but which are absent in mammalian tissues, and has been suggested to play an immunological role against microorganisms. However, the involvement of hITLN-1 in the pathogenesis of diffuse pulmonary diseases remains unknown. The aim of this study was to compare the hITLN-1 concentrations in the bronchoalveolar lavage (BAL) fluid of patients with diffuse pulmonary diseases. Methods The cell components and concentrations of hITLN-1 were analyzed in the BAL fluid of 8 patients with idiopathic chronic eosinophilic pneumonia (ICEP), 3 patients with drug-induced eosinophilic pneumonia, 4 patients with hypersensitivity pneumonitis (HP), 11 patients with sarcoidosis, 9 patients with cryptogenic organizing pneumonia, and 5 patients with idiopathic fibrosing interstitial pneumonia (fibrosing nonspecific interstitial pneumonia or usual interstitial pneumonia). Results The hITLN-1 concentrations in the BAL fluid of patients with ICEP and HP were higher than in those with other diseases. In the ICEP group, no significant difference was observed in the hITLN-1 concentrations of patients with or without a history of bronchial asthma. Conclusion The results of the present study suggest that hITLN-1 may be involved in the pathogenesis of ICEP and HP, and that an increase in the hITLN-1 concentration in the BAL fluid may represent a new biomarker for these diseases.
Enzyme therapy for functional bowel disease‐like post‐prandial distress

Post‐prandial gastrointestinal symptoms such as diarrhea, abdominal distension, flatulence, bloating and a feeling of fullness are common complaints of often unknown etiology and pathogenesis. There is a long history of trials reporting the successful use of products containing a variety of combinations of digestive enzymes including a number of randomized placebo‐controlled trials. We provide a narrative review of studies describing the use of multi‐digestive enzymes for symptoms consistent with irritable bowel syndrome. We describe clinical trials reported over the past 60 years including double‐blinded randomized, placebo‐controlled studies and recent trials that focused on post‐prandial diarrhea consistent with diarrhea‐predominant irritable bowel syndrome. Disaccharidase deficiencies or deficiencies of other carbohydrate digesting enzymes were excluded. Worldwide studies have generally reported success with multi‐enzyme preparations although none used a factorial design to identify subgroups or attempted to link specific symptom responses to specific components of therapy. Although there is a long history of the successful use of multi‐enzyme preparations for post‐prandial symptoms consistent with irritable bowel syndrome, long‐term studies using validated scoring systems and factorial designs are needed to confirm the results for specific symptoms and the components of the combination drugs received.
Standing on the Shoulders of Giants: The Springboard for Creativity and Wisdom

There is an interesting statement attributed to Isaac Newton: “If I have been able to see farther than others, it was because I stood on the shoulders of giants” (Peter, 1977, p. 458). Newton may have been considered a genius; however, this statement indicates that his insights were dependent on the knowledge of others, especially those who contributed tremendously to the advancement of ideas. It can be argued that no substantial progress is possible in any scholarly discipline without a good understanding of the works of others from the past. What it means to have an “understanding” or even a “good understanding” is certainly not without controversy and is clearly related to one’s epistemology or research paradigm (e.g., Noddings, 2007; Pring, 2004; see also Paul & Moores, 2012). Nevertheless, standing on the shoulders of giants can be related to debates on broad areas such as individual ingenuity versus social forces and the cultivation of habits of mind shaped by critical thinking. Of course, there are other constructs— including a balanced, thorough review of the literature for scholarly manuscripts.
NAC Transcription Factors ANAC087 and ANAC046 Control Distinct Aspects of Programmed Cell Death in the Arabidopsis Columella and Lateral Root Cap[OPEN]

Two NAC transcription factors, ANAC087 and ANAC046, control postmortem chromatin degradation in the lateral root cap and the life span of shed columella root cap cells in the rhizosphere. Programmed cell death in plants occurs both during stress responses and as an integral part of regular plant development. Despite the undisputed importance of developmentally controlled cell death processes for plant growth and reproduction, we are only beginning to understand the underlying molecular genetic regulation. Exploiting the Arabidopsis thaliana root cap as a cell death model system, we identified two NAC transcription factors, the little-characterized ANAC087 and the leaf-senescence regulator ANAC046, as being sufficient to activate the expression of cell death-associated genes and to induce ectopic programmed cell death. In the root cap, these transcription factors are involved in the regulation of distinct aspects of programmed cell death. ANAC087 orchestrates postmortem chromatin degradation in the lateral root cap via the nuclease BFN1. In addition, both ANAC087 and ANAC046 redundantly control the onset of cell death execution in the columella root cap during and after its shedding from the root tip. Besides identifying two regulators of developmental programmed cell death, our analyses reveal the existence of an actively controlled cell death program in Arabidopsis columella root cap cells.
Bilateral stereotactic lesions and chronic stimulation of the anterior thalamic nuclei for treatment of pharmacoresistant epilepsy

Background: The use of the anterior nucleus of thalamus (ANT) as a target for treatment of pharmacoresistant epilepsy is based on its crucial role in seizure propagation. We describe results of chronic bilateral ANT stimulation and bilateral ANT lesions in 31 patients with refractory epilepsy. Methods: ANT DBS was performed in 12 patients (group I) and bilateral stereotactic radiofrequency lesions of ANT were performed in 19 patients (group II). Targeting was based on stereotactic atlas information with correction of the final coordinates according to the location of anatomical landmarks and intraoperative microelectrode recording data. Results: Both groups were similar in age, gender, seizures frequency, and duration of disease. The median x, y, and z coordinates of ANT were found to be 2.9, 5, and 11 mm anterior, lateral, and superior to the mid-commissural point, respectively. Mean seizures reduction reached 80.3% in group of patients with ANT DBS with two nonresponders and 91.2% in group of patients with lesions. Five patients from group I and three patients from group II became seizure-free. The morbidity rate was low in both groups. Conclusions: Stereotactic anterior thalamotomy and chronic ANT stimulation are both effective for seizure control in epilepsy originated from frontal and temporal lobes. ANT lesions and stimulation were more effective for secondary-generalized seizures compared to simple partial seizures.
Cardiac sarcoidosis – an expert review for the chest physician

ABSTRACT Introduction: Sarcoidosis is a multisystem granulomatous disease predominantly affecting the lungs, with increased risk of cardiovascular disease, pulmonary hypertension and cardiac sarcoidosis (CS), the latter due to direct granuloma infiltration. Sarcoidosis is often managed by chest physicians who need to understand the diagnostic pathways and initial management plans for patients with cardiac involvement. Areas covered: The most serious consequence of CS is sudden cardiac death due to ventricular tachyarrhythmias or complete atrioventricular block. Additional complications include atrial arrhythmias and congestive cardiac failure. There are no internationally accepted screening pathways, but a combination of history, clinical examination and ECG detects up to 85% of cases. Newer modalities including signal-averaged ECG and speckle-tracking echocardiography increase identification of patients who require a definitive diagnosis. Early immunosuppression reduces the risk of conduction abnormalities and incidence of supraventricular arrhythmias. Management of ventricular arrhythmias requires antiarrhythmic medications followed by possible catheter ablation and device (ICD) implantation. Expert commentary: Prospective trials are underway to identify the optimum methods for screening, which will guide future international statements on indications for and methods of screening in CS.
Recent Progress and Advances in Stimuli-Responsive Polymers for Cancer Therapy

The conventional chemotherapeutic agents, used for cancer chemotherapy, have major limitations including non-specificity, ubiquitous biodistribution, low concentration in tumor tissue, and systemic toxicity. In recent years, owing to their unique features, polymeric nanoparticles have been widely used for the target-specific delivery of drugs in the body. Although polymeric nanoparticles have addressed a number of important issues, the bioavailability of drugs at the disease site, and especially upon cellular internalization, remains a challenge. A polymer nanocarrier system with a stimuli-responsive property (e.g., pH, temperature, or redox potential), for example, would be amenable to address the intracellular delivery barriers by taking advantage of pH, temperature, or redox potentials. With a greater understanding of the difference between normal and pathological tissues, there is a highly promising role of stimuli-responsive nanocarriers for drug delivery in the future. In this review, we highlighted the recent advances in different types of stimuli-responsive polymers for drug delivery.
A Systematic Review of Long Noncoding RNAs in Hepatocellular Carcinoma: Molecular Mechanism and Clinical Implications

Hepatocellular carcinoma (HCC) has the second highest mortality rate worldwide among all cancers. Previous studies have revealed the significant involvement of long noncoding RNAs (lncRNAs) in numerous human cancers including HCC. Both oncogenic and tumor repressive lncRNAs have been identified and implicated in the complex process of hepatocarcinogenesis. They can be further explored as prospective diagnostic, prognostic, and therapeutic markers for HCC. An in-depth understanding of lncRNAs' mechanism in HCC is therefore required to fully explore their potential role. In the current review, we will concentrate on the underlying function, molecular mechanisms, and potential clinical implications of lncRNA in HCC.
Effects of inter-character spacing on saccade programming in beginning readers and dyslexics

ABSTRACT The present study investigated the impact of inter-character spacing on saccade programming in beginning readers and dyslexic children. In two experiments, eye movements were recorded while dyslexic children, reading-age, and chronological-age controls, performed an oculomotor lateralized bisection task on words and strings of hashes presented either with default inter-character spacing or with extra spacing between the characters. The results of Experiment 1 showed that (1) only proficient readers had already developed highly automatized procedures for programming both left- and rightward saccades, depending on the discreteness of the stimuli and (2) children of all groups were disrupted (i.e., had trouble to land close to the beginning of the stimuli) by extra spacing between the characters of the stimuli, and particularly for stimuli presented in the left visual field. Experiment 2 was designed to disentangle the role of inter-character spacing and spatial width. Stimuli were made the same physical length in the default and extra-spacing conditions by having more characters in the default spacing condition. Our results showed that inter-letter spacing still influenced saccade programming when controlling for spatial width, thus confirming the detrimental effect of extra spacing for saccade programming. We conclude that the beneficial effect of increased inter-letter spacing on reading can be better explained in terms of decreased visual crowding than improved saccade targeting.
Cued by What We See and Hear: Spatial Reference Frame Use in Language

To what extent is the choice of what to say driven by seemingly irrelevant cues in the visual world being described? Among such cues, how does prior description affect how we process spatial scenes? When people describe where objects are located their use of spatial language is often associated with a choice of reference frame. Two experiments employing between-participants designs (N = 490) examined the effects of visual cueing and previous description on reference frame choice as reflected in spatial prepositions (in front of, to the left of, etc.) to describe pictures of object pairs. Experiment 1 examined the effects of visual and linguistic cues on spatial description choice through movement of object(s) in spatial scenes, showing sizeable effects of visual cueing on reference frame choice. Experiment 2 monitored eye movements of participants following a linguistic example description, revealing two findings: eye movement “signatures” associated with distinct reference frames as expressed in language, and transfer of these eye movement patterns just prior to spatial description for different (later) picture descriptions. Both verbal description and visual cueing similarly influence language production choice through manipulation of visual attention, suggesting a unified theory of constraints affecting spatial language choice.
A novel patient‐oriented numerical procedure for glaucoma drainage devices

The present work analyses the performance of four glaucoma drainage devices, by means of a novel patient‐oriented numerical procedure. The procedure is based on the three‐dimensional geometry reconstruction from the stacks of tomographic images of a human eye, at different angles, on meshing and on thermo‐fluid dynamics modelling activities, carried out on the reconstructed computational domain. The current three‐dimensional eye model considers anterior chamber (AC), trabecular meshwork, Schlemm's canal, and collector channels, making use of generalised porous medium approach for modelling ocular porous tissue and cavities. The intraocular pressure (IOP) management inside AC of human eye is analysed, by comparing the results obtained for four drainage devices implanted in a human eye for glaucoma treatment, ie, ExPRESS shunt, iStent inject, SOLX gold micro shunt, and the novel silicon shunt device. The numerical results allow predicting the effects of the installation of these implants on human eyes, in terms of IOP decrease, aqueous humour velocity, pressure, friction coefficient, and local Nusselt number, pointing out the clear distinction between pre‐operative and post‐operative eye conditions for different glaucoma surgical techniques.
Heparin‐induced thrombocytopenia‐associated thrombosis: from arterial to venous to venous limb gangrene

Heparin‐induced thrombocytopenia (HIT) is an acquired immune‐mediated hypercoagulability state that is strongly associated with thrombosis. During the 1970s and 1980s, the prevailing concept was that HIT was associated only with arterial thrombosis, through its unique pathogenesis via heparin‐dependent, platelet‐activating IgG antibodies. However, in 1990, when I began to encounter HIT in my clinical practice, I found that most such patients developed symptomatic venous thrombosis. This historical sketch summarizes some of the research that challenged the dogma of HIT being a mainly arterial prothrombotic disorder. Two studies – one a substudy of a randomized trial of post‐orthopedic surgery thromboprophylaxis, and the second a retrospective five‐hospital analysis of consecutive patients with positive test results for HIT antibodies – showed a marked predominance of venous over arterial thrombosis complicating HIT (~ 4 : 1). By the end of the 1990s, an even more dramatic manifestation of HIT‐associated venous thrombosis was recognized: venous limb gangrene. Here, ischemic limb necrosis occurs despite palpable arterial pulses, as a result of both macrovascular and microvascular venous thrombosis. The surprising explanation was natural anticoagulant impairment (severe depletion of protein C, a vitamin K‐dependent anticoagulant) resulting from treatment of HIT‐associated deep vein thrombosis with warfarin (vitamin K antagonist). These insights from HIT research helped to elucidate the pathogenesis of ischemic limb losses in other intense non‐HIT hypercoagulability states, including warfarin‐associated venous limb gangrene complicating cancer‐associated hypercoagulability, and symmetrical peripheral gangrene complicating disseminated intravascular coagulation of critical illness, in which proximate ‘shock liver’ helps to explain the profound failure of natural anticoagulant systems (protein C; antithrombin) in predisposing to peripheral limb microthrombosis in circulatory shock.
Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely Sampled Data

There is much interest in using genome-wide expression time series to identify circadian genes. However, the cost and effort of such measurements often limit data collection. Consequently, it is difficult to assess the experimental uncertainty in the measurements and, in turn, to detect periodic patterns with statistical confidence. We show that parametric bootstrapping and empirical Bayes methods for variance shrinkage can improve rhythm detection in genome-wide expression time series. We demonstrate these approaches by building on the empirical JTK_CYCLE method (eJTK) to formulate a method that we term BooteJTK. Our procedure rapidly and accurately detects cycling time series by combining information about measurement uncertainty with information about the rank order of the time series values. We exploit a publicly available genome-wide data set with high time resolution to show that BooteJTK provides more consistent rhythm detection than existing methods at typical sampling frequencies. Then, we apply BooteJTK to genome-wide expression time series from multiple tissues and show that it reveals biologically sensible tissue relationships that eJTK misses. BooteJTK is implemented in Python and is freely available on GitHub at https://github.com/alanlhutchison/BooteJTK.