Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination

Significance Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system (CNS), leading to irreversible deficits in young adults. Its pathophysiology is believed to be influenced by environmental determinants. As far back as the 1990s, it had been suggested that there is a correlation between the consumption of cow’s milk and the prevalence of MS. Here, we not only demonstrate that a high percentage of MS patients harbor antibodies to bovine casein but also that antibody cross-reactivity between cow’s milk and CNS antigens can exacerbate demyelination. Our data broaden the current understanding of how diet influences the etiology of MS and set the stage for combining personalized diet plans with disease-modifying treatment strategies.
Nanostructured polyelectrolyte complexes based on chitosan and sodium alginate containing rifampicin for the potential treatment of tuberculosis

Abstract Nanostructured polyelectrolyte complexes (nano PECs) were obtained by polyelectrolyte complexation technique from chitosan (CS) and sodium alginate (SA). Different polymer proportions were tested, as well as the addition order and homogenization type, to assess the influence on the nano PECs characteristics. The spherical shape and nanometric scale of the systems were observed by scanning electron microscopy (SEM). Nano PECs size, PDI, and zeta potential (ZP) ranged from 252 to 616 nm, from 0.22 to 0.73 and −50 to 30 mV, respectively. The increase of polymer proportion and the ultra-turrax homogenization led to the enlargement of particles size and PDI. However, no influence was observed on the ZP. The NP1s-Rb and NP4s-Rb, obtained through the sonicator with rifampicin (RIF) added before the CS and SA complexation, were selected due to the most promising characteristics of diameter (301 and 402 nm), PDI (0.27 and 0.26), and RIF incorporation (78 and 69%). The release profiles of RIF incorporated in both nano PECs were similar, with a sustained release of the drug for 180 min in phosphate buffer pH 7.2. The Weibull and the Korsmeyer–Peppas models better describe the RIF release from NP1s-Rb and NP4s-Rb, respectively, demonstrating that the release process was driven by different mechanism according to the particle composition. The nano PECs were lyophilized to prolong it stability and for possible nebulization. The addition of dextrose to the system allowed for resuspension after lyophilization. Therefore, with the results obtained, the incorporation of RIF in nano PECs based on CS and SA presents a promising system for the treatment of tuberculosis.
Venous outflow-targeted coil embolization of direct carotid-cavernous fistulas

Background Coil embolization is the mainstay treatment for carotid-cavernous fistulas (CCFs). However, few studies have reported entire occlusion of engorged veins to interrupt venous outflow. We report our experience with venous outflow-targeted coil embolization of direct CCFs. Methods We retrospectively reviewed all the patients diagnosed with direct CCFs treated with venous outflow-targeted coil embolization between November 2013 and February 2020. Venous outflow-targeted coil embolization of the CCFs was performed as follows. First, transarterial stent-assisted coil embolization of CCFs was performed. If the venous outflow to the engorged veins persisted after transarterial stent-assisted coil embolization, entire occlusion of the engorged veins and additional coil packing within the cavernous sinus were performed to interrupt the venous outflow. Results Ten patients had undergone venous outflow-targeted coil embolization, 6 women (60%) and 4 men (40%). Transfemoral cerebral angiography showed high-flow, direct CCFs in all the patients. Venous outflow occurred through the superior ophthalmic vein (SOV) in all the patients and was completely interrupted by the entire occlusion of the engorged veins with fibered coils. Three patients (30%) had undergone additional treatment in a supplementary manner because of recurrent symptoms (chemosis in 1 patient, faint tinnitus in 2 patients) in the early postprocedural period (1 to 4 weeks). All the symptoms were resolved on follow-up. No additional recurrence was found during follow-up (1–75 months). No peri-procedural complications were encountered. Conclusions Venous outflow-targeted coil embolization of CCFs would be a safe and effective treatment method.
Robust subtyping of non‐small cell lung cancer whole sections through MALDI mass spectrometry imaging

Subtyping of the most common non‐small cell lung cancer (NSCLC) tumor types adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) is still a challenge in the clinical routine and a correct diagnosis is crucial for an adequate therapy selection. Matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has shown potential for NSCLC subtyping but is subject to strong technical variability and has only been applied to tissue samples assembled in tissue microarrays (TMAs). To our knowledge, a successful transfer of a classifier from TMAs to whole sections, which are generated in the standard clinical routine, has not been presented in the literature as of yet.
Pneumatic dilation for the treatment of persistent post-laparoscopic fundoplication dysphagia: long-term efficacy and safety

ABSTRACT Background Post-laparoscopic fundoplication (LF) dysphagia occurs in 5%–17% of patients and optimal management remains a topic of expert discussion. We assessed the efficacy and safety of pneumatic dilation (PD) in patients with persistent post-lLF dysphagia. Methods Medical files of patients treated with PD for persistent post-fundoplication-associated dysphagia were reviewed. The primary outcome was long-term clinical success. Secondary endpoints were initial clinical success, dysphagia recurrence rate, and PD-related complication incidence. Results Overall, 46 patients (74% women, 57.9±11.9 years) underwent 74 PD (mean: 1.6±0.8). A 30 mm, 35 mm, and 40 mm balloon was used in 45.9%, 43.2%, and 10.8%, respectively, of dilations. Among 45 patients with available follow-up, the overall long-term success rate of PD was 31/45 (68.9% [55.4–82.4]). Initial clinical success was 36/45 (80% [68.3–91.7]). Dysphagia recurred in 9 patients (25%; 95%CI 10.9–39.1) and 4 of these were effectively treated with a new dilation. Among 14 non-responders to PD, 11 underwent surgery. Four complications (2 perforations, 1 muscularis dilaceration, and 1 peri-procedural bleeding) occurred in 4 patients (incidence: 5.4% [95%CI; 0.3–10.6]) and were treated with partially covered self-expandable esophageal stents andhemostatic clips. Conclusions Pneumatic balloon dilation for post-fundoplication-associated symptoms is associated with a satisfactory long-term success rate and acceptable safety profile.
Fyn and TOM1L1 are recruited to clathrin-coated pits and regulate Akt signaling

Ligand binding to EGF receptor (EGFR) triggers signaling and concomitant receptor recruitment to clathrin-coated pits. This study reveals that the signaling adaptor TOM1L1 recruits Fyn to a specialized subset of clathrin-coated pits and is required for SHIP2 recruitment and regulation of Akt signaling by EGFR.
Novel viruses discovered in the transcriptomes of agnathan fish

Agnatha is an ancient superclass of jawless fish that gave rise to all other vertebrates after diverging from chordates ~535 million years ago (mya) (Janvier, 1981). Currently, modern agnathans species include only 43 hagfish and 40 lampreys (Forey, 1995). These two orders have remained relatively morphologically unchanged since diverging 488– 443 mya (XianGuang et al., 2002). In vertebrates, viruses from birds and mammals are considerably better characterized than amphibian, reptile, and fish viruses (Essbauer & Ahne, 2001). As a subset of fish viruses, agnathan viruses are even more underexplored than teleost viruses. This lack of agnathan virus sampling limits our understanding of the complete fish virome and our ability to monitor emerging fish viruses in the aquaculture industry. Prior to nextgeneration sequencing and bioinformatics approaches, only one lamprey virus was known: the viral haemorrhagic septicaemia virus (VHSV) from the Rhabdoviridae family. Detection of this virus relied on molecular and serologybased methods (Gadd et al., 2010); however, more recent largescale metatranscriptomics enabled the discovery of eight new viruses in agnathans from the viral families Astroviridae, Caliciviridae, Hantaviridae, Hepeviridae, and Orthomyxoviridae (Shi et al., 2018), demonstrating the yet unsampled diversity of agnathan viruses. Through screening lesser explored viromes, new diverse viruses can be discovered in fish and higher vertebrates. The aim of this study was to identify and characterize novel viral sequences in agnathan RNAsequencing (RNAseq) datasets and determine the genetic relationship of these sequences to extant viruses.
Factors influencing emotional and behavioral problems in preschool children with cancer based on self-regulation shift theory

Objective The objective is to investigate the factors influencing emotional and behavioral problems in preschool children with cancer and to provide a scientific basis for developing predictive intervention strategies. Methods We recruited 375 preschool children with cancer, from March 2019 to February 2020, via convenience sampling. The self-regulation shift theory was implemented as a theoretical framework and a structural equation model was applied to construct and validate this framework and to analyze the relationships among various influencing factors. Results Children’s effortful control, parent–child attachment, the family environment, family upbringing, parents’ marital quality, parents’ education level, and social support significantly affected children’s emotions and behaviors. Additionally, children’s effortful control and parent–child attachment mediated the effect of the family environment, family upbringing, and parents’ marital quality on children’s emotions and behaviors. ” Conclusion This study identified several factors that influence children’s emotions and behaviors, which should be considered while developing predictive intervention strategies to promote children’s rehabilitation and improve parents’ education, thus offering improved support for children with cancer.
Role of vitamin D in ulcerative colitis: an update on basic research and therapeutic applications

ABSTRACT Introduction Vitamin D deficiency is common in patients with ulcerative colitis (UC). Moreover, vitamin D supplementation seems to contribute to disease relief. Nevertheless, the exact etiological link between vitamin D deficiency and UC is far from clear, and an agreement has not been reached on the frequency and dosage of vitamin D supplementation required. Areas covered This review will outline the possible role of vitamin D in the pathogenesis of UC and summarize the current state of clinical research on vitamin D. Literature was searched on PUBMED, with ‘Vitamin D,’ ‘Ulcerative colitis,’ ‘Vitamin D receptor,’ and ‘disease activity’ as MeSH Terms. Relevant information is presented in figures or tables. Expert opinion The etiological relationship between vitamin D and the onset of UC is still being researched. More high-quality double-blind randomized clinical studies are needed to determine the efficacy of vitamin D supplementation in the treatment of UC, whether as the main treatment or as an adjuvant treatment. Importantly, determining the dosage and frequency of vitamin D supplementation should be the main research direction in the future, and regional factors should also be fully considered in this respect.
Efficacy of Combined Mechanical and Chemical Decontamination Treatments on Smooth and Rough Titanium Surfaces and Their Effects on Osteoconduction: An Ex Vivo Study.

PURPOSE The aim of this ex vivo study was to assess the ability to remove oral biofilm by different combinations of mechanical and chemical treatments on smooth and rough titanium surfaces, as well as their impact on osteoconduction. MATERIALS AND METHODS Forty-eight sandblasted acid-etched (SLA) and 48 machined titanium disks were contaminated with oral bacterial biofilm and exposed to the following treatments: (1) titanium brush (TB), (2) TB + 40% citric acid (CA), (3) TB + 5.25% sodium hypochlorite (NaOCl), (4) air polishing with glycine powder (AP), (5) AP + 40% CA, and (6) AP + 5.25% NaOCl. Residual bacteria and chemical contamination were assessed using viable bacterial count assay, scanning electron microscopy (SEM), and x-ray spectroscopy (XPS). Human primary osteoblast (hOB) adhesion and osteocalcin (OC) release were also evaluated. RESULTS The microbiologic, SEM, and XPS analysis indicate a higher biofilm removal efficiency of combined mechanical-chemical treatments compared with exclusively mechanical approaches, especially on SLA surfaces. SEM analysis revealed significant alterations of surface microtopography on the disks treated with TB, while no changes were observed after AP treatment. OC release by hOBs was mainly decreased on disks treated with CA and NaOCl. CONCLUSION The combination of mechanical and chemical treatments provides effective oral biofilm removal on both SLA and machined implant surfaces. NaOCl and CA may have a negative effect on osteoblasts cultured on SLA samples.
Effect of Fines and Concentration on ZD-strength in Single- and Double-sided Twin-wire Forming

In order to investigate the effect of dewatering strategy on ZD-strength pilot-scale experiments have been performed. By using either a forming roll with a solid impermeable surface or a traditional perforated forming roll with vacuum the difference between single sided and double sided dewatering can be investigated. For both configurations the dewatering was completed on the forming roll, i.e. pure roll forming. As a result the double-sided dewatering will give rise to a dewatering centre in the middle of the sheet, which will not be present in the single- sided dewatered sheet. In addition, the effects of fines content in the furnish and the forming concentration have been investigated. The produced sheets were compared given their fines content, dewatering strategy and forming concentration. The comparison has been made both regarding absolute estimate of ZD-strength properties as well as the difference between the pilot-produced sheets and handsheets made with the same furnish.
Suppression of toxicity of the mutant huntingtin protein by its interacting compound, desonide

Significance Classical drug discovery identifies inhibitors that block the activities of pathogenic proteins. This typically relies on a measurable biochemical readout and accessible binding sites whose occupancy influences the activity of the target protein. These requirements make many pathogenic proteins “undruggable. ” Here, we report a strategy to target these undruggable proteins: screening for compounds that directly bind to the undruggable target and rescue disease-relevant phenotypes. These compounds may suppress the target’s pathogenic functions via direct binding to it. We applied this strategy to the mutant HTT protein, which is an undruggable protein that causes Huntington’s disease (HD). We revealed desonide, an FDAapproved drug, as a possible lead compound for HD drug discovery.
Vagally mediated heart rate variability, stress, and perceived social support: a focus on sex differences

Abstract Higher vagally mediated heart rate variability (vmHRV), reflecting vagal activity as indexed by heart function and lower stress vulnerability, is associated with higher perceived social support. Seeking social support is an adaptive stress response, and evolutionary theories suggest that females use this strategy more than males. The current study investigated the hypothesis that higher vmHRV is related to higher perceived social support under conditions of higher, relative to lower, stress, and that this association is most prominent in females. A healthy student sample (n = 143; 82 males, 61 females; mean age 19.9) completed the short version of the Medical outcomes study social support survey (MOS) and the Perceived stress scale (PSS). Activity in the high frequency band of heart rate variability (HF-HRV), deducted from five-minute resting electrocardiogram (ECG) recordings, indexed vmHRV. A moderation analysis was conducted, with PSS and sex as moderators of the association between vmHRV and MOS. Statistical effects were adjusted for age, education, physical activity, body mass index (BMI), alcohol and drug use, ECG-derived respiration (EDR), and mean heart rate. Higher PSS scores moderated the association between vmHRV and MOS in females but not males. Lower PSS scores did not moderate the relation between vmHRV and MOS. This suggests that higher vmHRV is associated with higher perceived social support under conditions of higher stress in females but not males, consistent with evolution of different stress management strategies in the sexes. The results may have implications for individualized intervention strategies for increasing vmHRV and perceived social support.
Rapid melt growth of silicon germanium for heterogeneousintegration on silicon

Silicon has made modern integrated circuit technology possible. As MOSFET gate lengths are scaled to 22nm and beyond, it has become apparent that new materials must be introduced to the silicon-based CMOS process for improved performance and functionality. This dissertation begins with a review of the MOSFET leakage current problem and presents one potential solution: Band-to-Band Tunneling (BTBT) transistors, which have the potential for steeper subthreshold slopes because they do not have the fundamental 'kT/q' limit in the rate at which conventional MOSFETs can be turned on or off. It is clear that these devices must be fabricated in materials with smaller bandgaps for improved performance. Silicon Germanium (SiGe) is one possible material system that could be used to fabricate enhanced BTBT transistors. Rapid Melt Growth (RMG) is a technique that has been used to recrystallize materials on Si substrates. RMG, however, has not previously been applied to SiGe, a binary alloy with large separation in the liquidus-solidus curve in its phase diagram. The development of process and experimental results for obtaining SiGe-on-insulator (SGOI) from bulk Si substrates through RMG are presented. The theory of RMG is analyzed and compositional profiles obtained during RMG of SiGe are modeled to understand why we were able to obtain high quality lateral compositionally graded SGOI substrates. The success of RMG SiGe suggests that the RMG technique can also be applied to III-V ternary and quaternary compounds with similar pseudo-binary phase diagrams. This opens up a wide range of material possibilities with the potential for novel applications in heterogeneous integration and 3-D device technology.
Ultrasonic Mealiness Classification of Apples

In modern agriculture, with its competitive markets, the importance of fruit quality is significant. Mealiness impairs the quality of apples and reduces their market value and price. Retailers are perfectly able to distinguish a mealy product from a fresh one, identifying it correctly with terms such as non-juicy, soft, etc. However, there is a need for a reliable method, incorporating appropriate sensors, for the nondestructive measurement and classification of apples by their mealiness; it needs to be designed for use by an untrained person. Several techniques have been suggested in the literature to determine the presence and degree of mealiness; they include destructive tests such as tensile tests, texture profile analysis, ultrasonic tests, etc., and some nondestructive sensory analysis methods, such as magnetic resonance techniques, electrical impedance, and NIR. The present paper suggests a system based on an ultrasonic energy absorbance method for nondestructive measurements of three mealiness levels – fresh, ripe and overripe – in Jonagold and Cox apples. The principle of operation is based on transmission of known ultrasonic energy into the fruit flesh and measuring the ultrasonic energy received after attenuation of the signal as it passes through the fruit tissue over a short distance across the fruit’s peel. The mechanical structure of the tissue, the physiochemical quality indices, or any change in the quality attributes of the fruit affects the energy of the received signal. The detected sound waves were analyzed in conjunction with the mealiness level of fruit. The results obtained suggest that it is possible to distinguish among the three mealiness levels in Jonagold fruits, but it was not applicable to the Cox fruits.
Deforestation reduces fruit and vegetable consumption in rural Tanzania

Significance Two billion people across the planet suffer from nutrient deficiencies. Dietary diversification is key to solving this problem, yet many food and nutrition security policies, especially in low- and middle-income countries, still focus on increasing agricultural production and access to sufficient calories as the main solution. But calories are not all equal. Here, we show how deforestation in Tanzania caused a reduction in fruit and vegetable consumption (of 14 g per person per day) and thus vitamin A adequacy of diets. Using a combination of regression and weighting analyses to generate quasi-experimental quantitative estimates of the impacts of deforestation on people’s food intake, our study establishes a causal link between deforestation and people’s dietary quality.
Adolescence is a sensitive period for prefrontal microglia to act on cognitive development

The prefrontal cortex (PFC) is a cortical brain region that regulates various cognitive functions. One distinctive feature of the PFC is its protracted adolescent maturation, which is necessary for acquiring mature cognitive abilities in adulthood. Here, we show that microglia, the brain’s resident immune cells, contribute to this maturational process. We find that transient and cell-specific deficiency of prefrontal microglia in adolescence is sufficient to induce an adult emergence of PFC-associated impairments in cognitive functions, dendritic complexity, and synaptic structures. While prefrontal microglia deficiency in adolescence also altered the excitatory-inhibitory balance in adult prefrontal circuits, there were no cognitive sequelae when prefrontal microglia were depleted in adulthood. Thus, our findings identify adolescence as a sensitive period for prefrontal microglia to act on cognitive development.
Cryo-EM structure and electrophysiological characterization of ALMT from Glycine max reveal a previously uncharacterized class of anion channels

Aluminum-activated malate transporters (ALMTs) form an anion channel family that plays essential roles in diverse functions in plants. Arabidopsis ALMT12, also named QUAC1 (quick anion channel 1), regulates stomatal closure in response to environmental stimuli. However, the molecular basis of ALMT12/QUAC1 activity remains elusive. Here, we describe the cryo-EM structure of ALMT12/QUAC1 from Glycine max at 3.5-Å resolution. GmALMT12/QUAC1 is a symmetrical dimer, forming a single electropositive T-shaped pore across the membrane. The transmembrane and cytoplasmic domains are assembled into a twisted two-layer architecture, with their associated dimeric interfaces nearly perpendicular. GmALMT12/QUAC1-mediated currents display rapid kinetics of activation/deactivation and a bell-shaped voltage dependency, reminiscent of the rapid (R)–type anion currents. Our structural and functional analyses reveal a domain-twisting mechanism for malate-mediated activation. Together, our study uncovers the molecular basis for a previously uncharacterized class of anion channels and provides insights into the gating and modulation of the ALMT12/QUAC1 anion channel.