Miracle-dz/UniFAR-FTUs huggingface dataset:
Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study

ABSTRACT Objectives: To report the association between testosterone treatment in hypogonadal men with hepatic steatosis, non-alcoholic fatty liver disease and cardiovascular disease (CVD). Methods: A prospective study was conducted to assess the physiological and functional performance of the long-term effects of testosterone undecanoate treatment on hepatic steatosis in 496 hypogonadal men. Two groups were studied, the treatment group (T-group) of 312 patients treated with TU 1000 mg every 12 weeks and followed for 8 years, and an untreated control group (C-group) of 184 patients. We evaluated liver functions and Fatty Liver Index (FLI) according to Mayo Clinic parameters and guidelines. Results: The T-group showed a decrease in the FLI (from a mean [SD] of 83.70 [12.15] to 67.12 [19.21]), bilirubin (from a mean [SD] of 1.69 [4.21] to 1.31 [1.91] mg/dL), triglycerides (from a mean [SD] of 254.87 [92.99] to 213.37 [66.91] mg/dL), and gamma-glutamyl-transferase (from a mean [SD] of 39.45 [11.51] to 29.11 [7.68] U/L) over the duration of the study. Other parameters were also reduced in the T-group such as body mass index (from a mean [SD] of 31.59 [4.51] to 29.50 [3.84] kg/m2) and waist circumference (from a mean [SD] of 107.51 [9.95] to 101.86 [9.28] cm). A total of 25 deaths (7.8%) were recorded in the T-group, among them, 11 (44%) were related to CVD. While in the C-group 28 deaths (15.2%) were recorded and all the reported deaths (100%) were related to CVD. Conclusions: The findings suggest that long-term testosterone therapy in hypogonadal men improves liver function. While, the physiological and functional improvements in the liver may be associated with a decrease in CVD-related mortality. Abbreviations ALT: alanine transaminase; AR: androgen receptor; AST: aspartate transaminase; BMI: body mass index; CVD: cardiovascular disease; FLI: Fatty Liver Index; γ-GT: gamma-glutamyl-transferase; MetS: metabolic syndrome; LDL: low-density lipoprotein; NAFLD: non-alcoholic fatty liver disease; RCT: randomised controlled trial; T2DM: type II diabetes mellitus; TT: total testosterone; TTh: testosterone therapy; TU: testosterone undecanoate; WC: waist circumference
Explaining support for international action against human rights abusers

Abstract How do international audiences decide whether to support action against human rights abusers? Foreign governments often respond to human rights abuses with naming and shaming, economic sanctions, or military action. Individuals make decisions about whether to support these actions with varying levels of information: Allegations might be sparse on details because of insufficient resources for reporting or because perpetrators conceal their behavior. Using a survey experiment that randomly varies the precision of details in human rights allegations, I found that respondents are highly supportive of action against human rights abusers regardless of the level of detail in reporting. Audiences especially support naming and shaming and imposing economic sanctions; they are more skeptical about intervening militarily. I found no evidence that precise fatality estimates, precise geographic location, or prompt reporting make respondents more willing to support these actions. Obfuscating details of human rights violations is not enough for perpetrators to escape international support for accountability.
Feed Intake, Milk Yield and Milk Composition of Fogera Cows Supplemented with Different Feeds

An experiment was conducted at Andassa Livestock Research Center in Amhara National Regional State (ANRS), Ethiopia, to evaluate the effect of different feed supplements on feed intake, milk yield and milk composition of Fogera cows. Twenty second parity Fogera cows with similar stage of lactation, mean initial body weight of 258 kg and an average initial milk yield of 0.86 kg cow -1 day -1 were selected from the herd of the research center. The experiment had four treatments with five replications each using a randomized complete block design to which initial body weight was used for blocking. The treatments were; 1. Animals fed on only hay harvested from natural pasture (Control), 2. Hay plus grass pea bran; 3. Hay plus wheat bran and 4. Hay plus commercial concentrate mix (maize grain + Noug seed cake + wheat bran + fish meal + salt). There were significant (P<0.01) differences in total dry matter, crude protein, neutral detergent fiber, acid detergent fiber and ash intakes among treatment groups. The overall milk yield (kg/cow/day) was 1.44; while fat, protein, total solid, solid-not-fat, and Ash composition of milk (%) were, 5.01, 3.07, 14.23, 9.22, 0.70, respectively. Milk yield was significantly different (P<0.01) between treatment groups. Except ash content all the milk compositions analysed were significantly different (P<0.01) among treatment groups. Supplementation of Fogera cows maintained on natural grass pasture with different feeds has an effect on feed intake, milk yield and milk composition.
Increasing the Channel Capacity: Parallel Data Transmission in a Testbed for Molecular Communication

In the field of molecular communication, molecules or other particles in the nanoscale are used to transmit information. This rather new communication paradigm has a large application potential, ranging from medicine to industrial systems. As testbeds are essential for evaluating the capabilities of this new form of communication, we improve an existing water-based testbed to achieve parallel data transmission within one communication channel in this work. To this end, two different information carriers, superparamagnetic iron oxide nanoparticles and fluorescent particles, are used to simultaneously transmit independent data streams. A detection system for fluorescent particles was specifically developed for the fluid molecular communication testbed. Using parallel data transmission in the modified testbed the channel capacity was nearly doubled in comparison to a transmission using only a single type of information particles.
How torturers are made: Evidence from Saddam Hussein’s Iraq

Abstract Because of the difficulties in researching torturers, little is known about how they are recruited, trained, and authorized, and how they morally justify their actions. This study examines oral history testimonies from 14 former torturers in Saddam Hussein’s Iraq. Torturers volunteered for jobs in the security services, and attributed their choice of career to psychologically traumatic childhoods. Torturers were trained to think of their victims as subhuman and dangerous, and to cultivate mercilessness as a type of strength. They carried out torture under direct orders, and two were tortured themselves when they failed to obey. They justified their actions morally by diffusing responsibility, blaming victims, and using just-cause thinking. Overall, the findings show that there is no single path to becoming a torturer, as there is great variation even among torturers from a single country. Much more research is needed to fully understand how torturers think and work.
2-Nitrophenol sensor-based wet-chemically prepared binary doped Co3O4/Al2O3 nanosheets by an electrochemical approach

Herein, the wet-chemical process (co-precipitation) was used to prepare nanosheets (NSs) of Co3O4/Al2O3 in an alkaline medium (pH ∼ 10.5). The synthesized NSs were totally characterized by Fourier-transform infrared spectroscopy (FTIR), ultraviolet visible spectroscopy (UV/vis), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and powder X-ray diffraction (XRD). The synthesized NSs were deposited onto a glassy carbon electrode (GCE) to prepare a very thin layer with a conducting binder for detecting 2-nitrophenol (2-NP) selectively by a reliable electrochemical method. The proposed chemical sensor exhibits good sensitivity (54.9842 μA μM−1 cm−2), long-term stability, and enhanced chemical response by electrochemical approaches. The resultant current is found to be linear over the concentration range (LDR) from 0.01 nM to 0.01 mM. The estimated detection limit (DL) is equal to 1.73 ± 0.02 pM. This study introduces a potential route for future sensitive sensor development with Co3O4/Al2O3 NSs by an electrochemical approach for the selective detection of hazardous and carcinogenic chemicals in environmental and health care fields.
Ear pinnae in a neotropical katydid (Orthoptera: Tettigoniidae) function as ultrasound guides for bat detection

Early predator detection is a key component of the predator-prey arms race, and has driven the evolution of multiple animal hearing systems. Katydids (Insecta) have sophisticated ears, each consisting of paired tympana on each foreleg that receive sound directly externally, and internally via a narrowing ear canal through the acoustic spiracle. These ears are pressure-time difference receivers capable of sensitive and accurate directional hearing across a wide frequency range, despite the small size of katydids. Many katydid species have cuticular pinnae which form cavities around the outer tympanal surfaces, but their function is unknown. We investigated pinnal function in the katydid Copiphora gorgonensis by combining experimental biophysics and numerical modelling using 3D ear geometries. Results show that the pinnae in C. gorgonensis do not assist in directional hearing for specific call frequencies, but instead pinnae act as ultrasound detector devices. Pinnae induced large sound pressure gains that enhanced sound detection at high ultrasonic frequencies (> 60 kHz), matching the echolocation range of co-occurring insectivorous bats. Comparing pinnal mechanics of sympatric katydid species supports these findings, and suggests that pinnae evolved in katydids primarily for enhanced predator detection. Audiograms (both behavioural and neural) and tympanal cavity resonances obtained from living specimens corroborate our findings.
Prolific Induction of IL-6 in Human Cells by SARS-CoV-2-derived Peptide is Attenuated by Recombinant Human Anti-inflammatory Cytokines made in planta

Development of efficient therapies for COVID-19 is the focus of intense research. The cytokine release syndrome was underlined as a culprit for severe outcomes in COVID-19 patients. Interleukin-6 (IL-6) plays a crucial role in human immune responses and elevated IL-6 plasma levels have been associated with the exacerbated COVID-19 pathology. Since non-structural protein 10 (NSP10) of SARS-CoV-2 has been implicated in the induction of IL-6, we designed Peptide (P)1, containing sequences corresponding to amino acids 68-96 of NSP10, and examined its effect on cultured human cells. Treatment with P1 strongly increased IL-6 secretion by the lung cancer cell line NCI-H1792 and the breast cancer cell line MDA-MB-231 and revealed profound cytotoxic activity on Caco-2 colorectal adenocarcinoma cells. Treatment with P2, harbouring a mutation in the zinc knuckle motif of NSP10, caused no IL-6 induction and no cytotoxicity. Pre-treatment with plant-produced human anti-inflammatory cytokines IL-37b and IL-38 effectively mitigated the induction of IL-6 secretion. Our results suggest a role for the zinc knuckle motif of NSP10 in the onset of increased IL-6 plasma levels of COVID-19 patients and for IL-37b and IL-38 as therapeutics aimed at attenuating the cytokine release syndrome.
Single nucleotide substitutions effectively block Cas9 and allow for scarless genome editing in Caenorhabditis elegans

In Caenorhabditis elegans, germline injection of Cas9 complexes is reliably used to achieve genome editing through homology-directed repair of Cas9-generated DNA breaks. To prevent Cas9 from targeting repaired DNA, additional blocking mutations are often incorporated into homologous repair templates. Cas9 can be blocked either by mutating the PAM sequence that is essential for Cas9 activity or by mutating the guide sequence that targets Cas9 to a specific genomic location. However, it is unclear how many nucleotides within the guide sequence should be mutated, since Cas9 can recognize “off-target” sequences that are imperfectly paired to its guide. In this study, we examined whether single-nucleotide substitutions within the guide sequence are sufficient to block Cas9 and allow for efficient genome editing. We show that a single mismatch within the guide sequence effectively blocks Cas9 and allows for recovery of edited animals. Surprisingly, we found that a low rate of edited animals can be recovered without introducing any blocking mutations, suggesting a temporal block to Cas9 activity in C. elegans. Furthermore, we show that the maternal genome of hermaphrodite animals is preferentially edited over the paternal genome. We demonstrate that maternally provided haplotypes can be selected using balancer chromosomes and propose a method of mutant isolation that greatly reduces screening efforts post-injection. Collectively, our findings expand the repertoire of genome editing strategies in C. elegans and demonstrate that extraneous blocking mutations are not required to recover edited animals when the desired mutation is located within the guide sequence.
Global mapping of the energetic and allosteric landscapes of protein binding domains

Allosteric communication between distant sites in proteins is central to nearly all biological regulation but still poorly characterised for most proteins, limiting conceptual understanding, biological engineering and allosteric drug development. Typically only a few allosteric sites are known in model proteins, but theoretical, evolutionary and some experimental studies suggest they may be much more widely distributed. An important reason why allostery remains poorly characterised is the lack of methods to systematically quantify long-range communication in diverse proteins. Here we address this shortcoming by developing a method that uses deep mutational scanning to comprehensively map the allosteric landscapes of protein interaction domains. The key concept of the approach is the use of ‘multidimensional mutagenesis’: mutational effects are quantified for multiple molecular phenotypes—here binding and protein abundance—and in multiple genetic backgrounds. This is an efficient experimental design that allows the underlying causal biophysical effects of mutations to be accurately inferred en masse by fitting thermodynamic models using neural networks. We apply the approach to two of the most common human protein interaction domains, an SH3 domain and a PDZ domain, to produce the first global atlases of allosteric mutations for any proteins. Allosteric mutations are widely dispersed with extensive long-range tuning of binding affinity and a large mutational target space of network-altering ‘edgetic’ variants. Mutations are more likely to be allosteric closer to binding interfaces, at Glycines in secondary structure elements and at particular sites including a chain of residues connecting to an opposite surface in the PDZ domain. This general approach of quantifying mutational effects for multiple molecular phenotypes and in multiple genetic backgrounds should allow the energetic and allosteric landscapes of many proteins to be rapidly and comprehensively mapped.
Incidental reinstatement of faces and scenes in medial temporal lobe subregions during word recognition

During associative retrieval, the brain reinstates neural representations that were present during encoding. The human medial temporal lobe (MTL) with its subregions hippocampus (HC), perirhinal cortex (PRC), and parahippocampal cortex (PHC) plays a central role in neural reinstatement. Previous studies have given compelling evidence for reinstatement in the MTL during explicitly instructed associative retrieval. High-confident recognition may be similarly accompanied by recollection of associated information from the encoding context. It is unclear, however, whether high-confident recognition memory elicits reinstatement in the MTL even in the absence of an explicit instruction to retrieve associated information. Here, we addressed this open question using high-resolution fMRI. Twenty-eight male and female human volunteers engaged in a recognition memory task for words that they had previously encoded together with faces and scenes. Using complementary uni- and multivariate approaches, we show that MTL subregions including the PRC, PHC, and HC differentially reinstate category-specific representations during high-confident word recognition, even though no explicit instruction to retrieve the associated category was given. This constitutes novel evidence that high-confident recognition memory is accompanied by incidental reinstatement of associated category information in MTL subregions, and supports a functional model of the MTL that emphasises content-sensitive representations during both encoding and retrieval.
Early stage of Spinocerebellar Ataxia Type 1 (SCA1) progression exhibits region- and cell-specific pathology and is partially ameliorated by Brain Derived Neurotrophic Factor (BDNF)

Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by an abnormal expansion of CAG repeats in the gene Ataxin1 (ATXN1) and characterized by motor deficits, cognitive decline, changes in affect, and premature lethality. Due to the severe cerebellar degeneration in SCA1, the pathogenesis of Purkinje cells has been the main focus of previous studies. However, mutant ATXN1 is expressed throughout the brain, and pathology in brain regions beyond the cerebellar cortex likely contribute to the symptoms of SCA1. Here, we investigate early-stage SCA1 alterations in neurons, astrocytes, and microglia in clinically relevant brain regions including hippocampus and brain stem of Atxn1154Q/2Q mice, a knock-in mouse model of SCA1 expressing mutant ATXN1 globally.Our results indicate shared and brain region specific astrocyte pathology early in SCA1 preceding neuronal loss. We found reduced expression of homeostatic astrocytic genes Kcnj10, Aqp4, Slc1a2 and Gja1, all of which are key for neuronal function in the hippocampus and brain stem. These gene expression changes did not correlate with classical astrogliosis. Neuronal and microglial numbers were largely unaltered at this early stage of SCA1 with the exception of cerebellar white matter, where we found significant reduction in microglial density, and the brain stem where we detected an increase in microglial cell counts.Brain-derived neurotrophic factor (BDNF) is a growth factor important for the survival and function of neurons with broad therapeutic potential for many brain diseases. We report here that BDNF expression is decreased in cerebellum and medulla of patients with SCA1. Moreover, we found that BDNF had dual effect on SCA1 and wild-type mice. Motor performance, strategy development, hippocampal neurogenesis, and expression of astrocyte homeostatic genes in the hippocampus were ameliorated in BDNF-treated SCA1 mice and further enhanced in BDNF-treated wild-type mice. On the other hand, BDNF had a negative effect on memory recall and expression of homeostatic genes in the brain stem astrocytes both in wild-type and in SCA1 mice.
Development of a novel, pan-variant aerosol intervention for COVID-19

To develop a universal strategy to block SARS-CoV-2 cellular entry and infection represents a central aim for effective COVID-19 therapy. The growing impact of emerging variants of concern increases the urgency for development of effective interventions. Since ACE2 is the critical SARS-CoV-2 receptor and all tested variants bind to ACE2, some even at much increased affinity (see accompanying paper), we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here we show that intranasal administration of APN01 in a mouse model of SARS-CoV-2 infection dramatically reduced weight loss and prevented animal death. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers can now be initiated, with subsequent Phase II testing in individuals with SARS-CoV-2 infection. This strategy could be used to develop a viable and rapidly actionable therapy to prevent and treat COVID-19, against all current and future SARS-CoV-2 variants. One Sentence Summary Preclinical development and evaluation of aerosolized soluble recombinant human ACE2 (APN01) administered as a COVID-19 intervention is reported.
The Synthesis of Unpaired Underwater Images for Monocular Underwater Depth Prediction

Underwater depth prediction plays an important role in underwater vision research. Because of the complex underwater environment, it is extremely difficult and expensive to obtain underwater datasets with reliable depth annotation. Thus, underwater depth map estimation with a data-driven manner is still a challenging task. To tackle this problem, we propose an end-to-end system including two different modules for underwater image synthesis and underwater depth map estimation, respectively. The former module aims to translate the hazy in-air RGB-D images to multi-style realistic synthetic underwater images while retaining the objects and the structural information of the input images. Then we construct a semi-real RGB-D underwater dataset using the synthesized underwater images and the original corresponding depth maps. We conduct supervised learning to perform depth estimation through the pseudo paired underwater RGB-D images. Comprehensive experiments have demonstrated that the proposed method can generate multiple realistic underwater images with high fidelity, which can be applied to enhance the performance of monocular underwater image depth estimation. Furthermore, the trained depth estimation model can be applied to real underwater image depth map estimation. We will release our codes and experimental setting in https://github.com/ZHAOQIII/UW_depth.
Akkermansia Muciniphila Potentiates the Antitumor Efficacy of FOLFOX in Colon Cancer

FOLFOX (oxaliplatin, fluorouracil and calcium folinate) is the first-line chemotherapy regimen for colon cancer therapy in the clinic. It provides superior efficacy than oxaliplatin alone, but the underlying mechanism remains unclear. In the present study, pharmacomicrobiomics integrated with metabolomics was conducted to uncover the role of the gut microbiome behind this. First, in vivo study demonstrated that FOLFOX exhibited better efficacy than oxaliplatin alone in colon cancer animal models. Second, 16S rDNA gene sequencing analysis showed that the abundance of Akkermansia muciniphila (A. muciniphila) remarkably increased in the FOLFOX treated individuals and positively correlated with the therapeutic effect. Third, further exploration confirmed A. muciniphila colonization significantly enhanced the anti-cancer efficacy of FOLFOX. Last, metabolomics analysis suggested dipeptides containing branched-chain amino acid (BCAA) might be responsible for gut bacteria mediated FOLFOX efficacy. In conclusion, our study revealed the key role of A. muciniphila in mediating FOLFOX efficacy, and manipulating A. muciniphila might serve as a novel strategy for colon cancer therapy.