Miracle-dz/UniFAR-FTUs huggingface dataset:
MRNIP interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice

Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet‐like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body chromatin during diplotene. We demonstrate that Mrnip−/− spermatocytes have impaired DNA double‐strand break (DSB) repair, they display reduced sex body formation and defective MSCI. We show that Mrnip−/− undergoes critical meiocyte loss at the diplotene stage. Furthermore, we determine that DNA DSBs (induced by SPO11) and synapsis initiation (facilitated by SYCP1) precede Mrnip expression in testes. Altogether, our findings indicate that in addition to an emerging role in DNA DSB repair, MRNIP has an essential function in spermatogenesis during meiosis I by forming drop‐like accumulations interacting with the sex body.
Is there a ‘bipolar iceberg’ in UK primary care psychological therapy services?

Abstract Background Improving Access to Psychological Therapies (IAPT) is a primary care therapy service commissioned by England's National Health Service (NHS) for people with unipolar depression and anxiety-related disorders. Its scope does not extend to ‘severe mental illness’, including bipolar disorders (BD), but evidence suggests there is a high BD prevalence in ostensibly unipolar major depressive disorder (uMDD) samples. This study aimed to indicate the prevalence and characteristics of people with BD in a naturalistic cohort of IAPT patients. Methods 371 participants were assessed before initiating therapy. Participants were categorised by indicated diagnoses: BD type-I (BD-I) or type-II (BD-II) as defined using a DSM diagnostic interview, bipolar spectrum (BSp, not meeting diagnostic criteria but exceeding BD screening thresholds), lifetime uMDD or other. Information about psychiatric history and co-morbidities was examined, along with symptoms before and after therapy. Results 368 patients provided sufficient data to enable classification. 10% of participants were grouped as having BD-I, 20% BD-II, 40% BSp, 25% uMDD and 5% other. BD and uMDD participants had similar demographic characteristics, but patients meeting criteria for BD-I/BD-II had more complex psychiatric presentations. All three ‘bipolar’ groups had particularly high rates of anxiety disorders. IAPT therapy receipt was comparable between groups, as was therapy response (F9704 = 1.113, p = 0.351). Conclusions Notwithstanding the possibility that bipolar diathesis was overestimated, findings illustrate a high prevalence of BD in groups of people notionally with uMDD or anxiety. As well as improving the detection of BD, further substantive investigation is required to establish whether individuals affected by BD should be eligible for primary care psychological intervention.
Commentary: Visual field testing: A distressing or an unpleasant experience!

Glaucoma is progressive neurodegeneration of retinal ganglion cells and their axons, characterized by a specific pattern of visual field loss and optic nerve head damage. There is no current cure for glaucoma. It is best managed with early diagnosis and timely medical management. The two most important factors to consider when determining whether a patient has glaucoma and the severity of the disease are the structural appearance of the optic nerve and the presence of functional damage as detected by visual field testing. It is crucial that accurate and reliable results are obtained during visual field testing for patients to receive the most appropriate management.
Development and Characterization of Celecoxib Solid Self-nanoemulsifying Drug Delivery Systems (S-SNEDDS) Prepared Using Novel Cellulose-Based Microparticles as Adsorptive Carriers

Self-nanoemulsifying drug delivery systems (SNEDDS) represent an interesting platform for improving the oral bioavailability of poorly soluble lipophilic drugs. While Liquid-SNEDDS (L-SNEDDS) effectively solubilize the drug in vivo, they have several drawbacks, including poor storage stability. Solid-SNEDDS (S-SNEDDS) combine the advantages of L-SNEDDS with those of solid dosage forms, particularly stability. The aim of the present study was to convert celecoxib L-SNEDDS into S-SNEDDS without altering their release behavior. Various commercially available adsorptive carrier materials were investigated, as well as novel cellulose-based microparticles prepared by spray drying from an aqueous dispersion containing Diacel® 10 and methyl cellulose or gum arabic as a binder prior to their use. Particle size and morphology of the carrier materials were screened by scanning electron microscopy and their effects on the loading capacity for L-SNEDDS were investigated, and comparative in vitro dissolution studies of celecoxib L-SNEDDS and the different S-SNEDDS were performed immediately after preparation and after 3 months of storage. Among the adsorptive carrier materials, the novel cellulose-based microparticles were found to be the most suitable for the preparation of celecoxib S-SNEDDS from L-SNEDDS, enabling the preparation of a solid, stable formulation while preserving the in vitro release performance of the L-SNEDDS formulation.
Joint semiparametric models for case‐cohort designs

Two‐phase studies such as case‐cohort and nested case‐control studies are widely used cost‐effective sampling strategies. In the first phase, the observed failure/censoring time and inexpensive exposures are collected. In the second phase, a subgroup of subjects is selected for measurements of expensive exposures based on the information from the first phase. One challenging issue is how to utilize all the available information to conduct efficient regression analyses of the two‐phase study data. This paper proposes a joint semiparametric modeling of the survival outcome and the expensive exposures. Specifically, we assume a class of semiparametric transformation models and a semiparametric density ratio model for the survival outcome and the expensive exposures, respectively. The class of semiparametric transformation models includes the proportional hazards model and the proportional odds model as special cases. The density ratio model is flexible in modeling multivariate mixed‐type data. We develop efficient likelihood‐based estimation and inference procedures and establish the large sample properties of the nonparametric maximum likelihood estimators. Extensive numerical studies reveal that the proposed methods perform well under practical settings. The proposed methods also appear to be reasonably robust under various model mis‐specifications. An application to the National Wilms Tumor Study is provided.
Advanced diagnostics in inflammatory cardiomyopathy for personalized therapeutic decision-making.

of and/or clinical manifestations ranging from courses to symptoms of chest progressive heart failure, and to fulminant forms with cardiogenic shock or life-threatening ventricular arrhyth-mia. Due to the highly variable pathoaetiology, Abstract Pathological mechanisms of viral and postinfectious autoimmunity in myocarditis and in ﬂ ammatory cardiomyopathy. A genetic predisposition is sup-posed for persistence of virus and/or in ﬂ ammation. Advanced diagnostics including endomyocardial biopsies are essential for a pathologically-proven diagnosis as the basis for a speci ﬁ c, causal and personalized therapy.
Key Point Sensitive Loss for Long-Tailed Visual Recognition

For long-tailed distributed data, existing classification models often learn overwhelmingly on the head classes while ignoring the tail classes, resulting in poor generalization capability. To address this problem, we thereby propose a new approach in this paper, in which a key point sensitive (KPS) loss is presented to regularize the key points strongly to improve the generalization performance of the classification model. Meanwhile, in order to improve the performance on tail classes, the proposed KPS loss also assigns relatively large margins on tail classes. Furthermore, we propose a gradient adjustment (GA) optimization strategy to re-balance the gradients of positive and negative samples for each class. By virtue of the gradient analysis of the loss function, it is found that the tail classes always receive negative signals during training, which misleads the tail prediction to be biased towards the head. The proposed GA strategy can circumvent excessive negative signals on tail classes and further improve the overall classification accuracy. Extensive experiments conducted on long-tailed benchmarks show that the proposed method is capable of significantly improving the classification accuracy of the model in tail classes while maintaining competent performance in head classes.
GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/β‐catenin and ALK5/SMAD2/3 pathways

GDF11 is a member of the TGF‐β superfamily that was recently implicated as potential “rejuvenating” factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue.
Gruffi: an algorithm for computational removal of stressed cells from brain organoid transcriptomic datasets

Organoids enable in vitro modeling of complex developmental processes and disease pathologies. Like most 3D cultures, organoids lack sufficient oxygen supply and therefore experience cellular stress. These negative effects are particularly prominent in complex models, such as brain organoids, and can affect lineage commitment. Here, we analyze brain organoid and fetal single‐cell RNA sequencing (scRNAseq) data from published and new datasets, totaling about 190,000 cells. We identify a unique stress signature in the data from all organoid samples, but not in fetal samples. We demonstrate that cell stress is limited to a defined subpopulation of cells that is unique to organoids and does not affect neuronal specification or maturation. We have developed a computational algorithm, Gruffi, which uses granular functional filtering to identify and remove stressed cells from any organoid scRNAseq dataset in an unbiased manner. We validated our method using six additional datasets from different organoid protocols and early brains, and show its usefulness to other organoid systems including retinal organoids. Our data show that the adverse effects of cell stress can be corrected by bioinformatic analysis for improved delineation of developmental trajectories and resemblance to in vivo data.
A graded approach in East Asian personalized lower blepharoplasty: A retrospective study spanning 12 years

Purpose: The aim of the study was to describe a graded approach for assessment and specific treatment, which can achieve satisfactory postoperative result in East Asian personalized lower blepharoplasty. Methods: We reviewed 913 patients who underwent lower blepharoplasty from 2008 to 2020. We preoperatively classified patients with different characteristics to provide personalized treatment. Results: There were 163 patients with fat herniation but no lower eyelid skin laxity, 259 patients with lower eyelid skin laxity accompanied by mild fat herniation, 313 patients with sagging lower eyelid skin accompanied by mild fat herniation and tear troughs, and a total of 178 patients with sagging skin accompanied by moderate to severe fat herniation and tear troughs. The overall success rate was 97.81%. Postoperative complications included the following: conjunctival chemosis, dry eye symptoms, and more. Conclusion: For East Asian patients with different characteristics, we achieved satisfactory postoperative results through accurate preoperative clinical grading and personalized surgical plans. The success of the operation not only depends on correct manipulation during the procedure but also on the surgeon’s accurate assessment and full grasp of the anatomy of each patient preoperatively.
Network analysis reveals aggregation behaviour for an endangered predator at an offshore island

Abstract Site fidelity and aggregation behaviour were assessed for giant sea bass Stereolepis gigas (GSB) at Santa Barbara Island, California, USA, from 2018 to 2020. Results indicate seasonal variation in GSB presence, and network analyses revealed a preferred location in a spatially constrained pattern, indicative of aggregation behaviour. Results show GSB aggregated annually during spawning months in the same location, confirming the first known aggregation of GSB at Santa Barbara Island. Identifying and monitoring aggregation sites is vital to ensuring proper protection and ultimate recovery for this protected species in a changing climate.
Video meeting signals: Experimental evidence for a technique to improve the experience of video conferencing

We found evidence from two experiments that a simple set of gestural techniques can improve the experience of online meetings. Video conferencing technology has practical benefits, but psychological costs. It has allowed industry, education and social interactions to continue in some form during the covid-19 lockdowns. But it has left many users feeling fatigued and socially isolated, perhaps because the limitations of video conferencing disrupt users’ ability to coordinate interactions and foster social affiliation. Video Meeting Signals (VMS™) is a simple technique that uses gestures to overcome some of these limitations. First, we carried out a randomised controlled trial with over 100 students, in which half underwent a short training session in VMS. All participants rated their subjective experience of two weekly seminars, and transcripts were objectively coded for the valence of language used. Compared to controls, students with VMS training rated their personal experience, their feelings toward their seminar group, and their perceived learning outcomes as significantly higher. Also, they were more likely to use positive language and less likely to use negative language. A second, larger experiment replicated the first, and added a condition where groups were given a version of the VMS training but taught to use emoji response buttons rather than gestures to signal the same information. The emoji-trained groups did not experience the same improvement as the VMS groups. By exploiting the specific benefits of gestural communication, VMS has great potential to overcome the psychological problems of group video meetings.
Autonomic indices and loss-of-control eating in adolescents: an ecological momentary assessment study

Abstract Background Loss-of-control (LOC) eating commonly develops during adolescence, and it predicts full-syndrome eating disorders and excess weight gain. Although negative emotions and emotion dysregulation are hypothesized to precede and predict LOC eating, they are rarely examined outside the self-report domain. Autonomic indices, including heart rate (HR) and heart rate variability (HRV), may provide information about stress and capacity for emotion regulation in response to stress. Methods We studied whether autonomic indices predict LOC eating in real-time in adolescents with LOC eating and body mass index (BMI) ⩾70th percentile. Twenty-four adolescents aged 12–18 (67% female; BMI percentile mean ± standard deviation = 92.6 ± 9.4) who reported at least twice-monthly LOC episodes wore biosensors to monitor HR, HRV, and physical activity for 1 week. They reported their degree of LOC after all eating episodes on a visual analog scale (0–100) using a smartphone. Results Adjusting for physical activity and time of day, higher HR and lower HRV predicted higher self-reported LOC after eating. Parsing between- and within-subjects effects, there was a significant, positive, within-subjects association between pre-meal HR and post-meal LOC rating. However, there was no significant within-subjects effect for HRV, nor were there between-subjects effects for either electrophysiologic variable. Conclusions Findings suggest that autonomic indices may either be a marker of risk for subsequent LOC eating or contribute to LOC eating. Linking physiological markers with behavior in the natural environment can improve knowledge of illness mechanisms and provide new avenues for intervention.
Quasi-commutative cochains in algebraic topology

We introduce a new algebraic concept of an algebra which is "almost" commutative (more precisely "quasi-commutative differential graded algebra" or ADGQ, in French). We associate to any simplicial set X an ADGQ - called D(X) - and show how we can recover the homotopy type of the topological realization of X from this algebraic structure (assuming some finiteness conditions). The theory is sufficiently general to include also ringed spaces X. The construction is by itself interesting since it uses the difference calculus (instead of the differential calculus of Sullivan's theory) and a new type of tensor product, called "reduced tensor product". Although we dont have a minimal model yet, it is relatively easy to define the cup i-products and the Steenrod operations on the category of ADGQ's. Homotopy groups can be deduced from the "iterated Hochschild homology" of D(X). The determination of the homotopy type from this algebraic structure uses in an essential way recent results of M. Mandell.
Sacubitril/valsartan in heart failure: efficacy and safety in and outside clinical trials

Heart failure (HF) treatment has changed substantially over the last 30 years, leading to significant reductions in mortality and hospital admissions in patients with HF with reduced ejection fraction (HFrEF). Currently, the optimization of guideline‐directed chronic HF therapy remains the mainstay to further improve quality of life, mortality, and HF hospitalizations for patients with HFrEF. The angiotensin receptor‐neprilysin inhibitor sacubitril/valsartan (S/V) has an important role in the treatment of patients with HFrEF. The PARADIGM‐HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) randomized controlled trial has established solid evidence for the treatment of HFrEF in various subgroups. Apart from HFrEF, several studies have been conducted using S/V in various indications: patients hospitalized with acute decompensated HF, HF with preserved ejection fraction, acute myocardial infarction with reduced ejection fraction, uncontrolled and resistant hypertension, and chronic kidney disease. Data from the German Institute for Drug Use Evaluation reveal that implementation of S/V has increased steadily over time and, by the end of 2021, an estimated 266 000 patients were treated with S/V in Germany. The estimated cumulative real‐world patient exposure is >5.5 million patient‐treatment years worldwide. The number of patients treated with S/V largely exceeds the number of patients treated in clinical trials, and the current indication for S/V is larger than the strict inclusion/exclusion criteria of the randomized trials. Especially elderly patients, women, and patients with more and more severe comorbidities are underrepresented in the clinical trials. We therefore aimed to summarize the importance of S/V in HF in terms of efficacy and safety in clinical trials and daily clinical practice.
Elongation enhances encounter rates between phytoplankton in turbulence

Significance Encounters between phytoplankton cells are among the key microphysical processes that control global biogeochemical cycles in the ocean, e.g., through the formation of marine snow. Current models of marine snow formation that account for turbulence in the oceans represent cells as spheres, yet phytoplankton cells are often highly elongated with typical aspect ratios of five and greater. Here, we combine simulations and theory to comprehensively quantify encounter rates between elongated phytoplankton in turbulence. Remarkably, we show that encounter rates between the most elongated cells are up to 10-fold higher than between spherical cells. We predict that these enhanced encounter rates accelerate marine snow formation and thus offer a mechanistic explanation for the rapid clearance of phytoplankton blooms.
Nanostructured Cyclodextrin-Mediated Surface for Capacitive Determination of Cortisol in Multiple Biofluids

The aim of this work is to develop a reusable polypropylene glycol (PPG):β-cyclodextrin (βCD) biosensor for cortisol detection. To achieve the most stable support for βCD, we developed two PPG surfaces. The first surface is based on a gold surface modified with SAM of 3-mercaptopropionic acid (3MPA), and the second surface is based on a glassy carbon surface grafted with 4-carboxyphenyl diazonium salt. We characterized both surfaces by EIS, XPS, and ATR-FTIR and evaluated the stability and reusability of each surface. We found the GC-carboxyphenyl-PPG:βCD is stable for at least 1 month. We have also demonstrated the reusability of the surface up to 10 times. In detecting cortisol, we used a nonfaradaic electrochemical impedance capacitive model to interpret the surface confirmation changes. We achieved sensitive detection of cortisol in PBS buffer, urine, and saliva with limit of detection of 2.13, 1.29, and 1.33 nM, respectively.
Energy Interplay in Materials: Unlocking Next‐Generation Synchronous Multisource Energy Conversion with Layered 2D Crystals

Layered 2D crystals have unique properties and rich chemical and electronic diversity, with over 6000 2D crystals known and, in principle, millions of different stacked hybrid 2D crystals accessible. This diversity provides unique combinations of properties that can profoundly affect the future of energy conversion and harvesting devices. Notably, this includes catalysts, photovoltaics, superconductors, solar‐fuel generators, and piezoelectric devices that will receive broad commercial uptake in the near future. However, the unique properties of layered 2D crystals are not limited to individual applications and they can achieve exceptional performance in multiple energy conversion applications synchronously. This synchronous multisource energy conversion (SMEC) has yet to be fully realized but offers a real game‐changer in how devices will be produced and utilized in the future. This perspective highlights the energy interplay in materials and its impact on energy conversion, how SMEC devices can be realized, particularly through layered 2D crystals, and provides a vision of the future of effective environmental energy harvesting devices with layered 2D crystals.