Miracle-dz/UniFAR-FTUs huggingface dataset:
Artificial Intelligence in Lung Cancer: Bridging the Gap Between Computational Power and Clinical Decision-Making

Lung cancer remains the most common cause of cancer death worldwide. Recent advances in lung cancer screening, radiotherapy, surgical techniques, and systemic therapy have led to increasing complexity in diagnosis, treatment decision-making, and assessment of recurrence. Artificial intelligence (AI)–based prediction models are being developed to address these issues and may have a future role in screening, diagnosis, treatment selection, and decision-making around salvage therapy. Imaging plays an essential role in all components of lung cancer management and has the potential to play a key role in AI applications. Artificial intelligence has demonstrated value in prognostic biomarker discovery in lung cancer diagnosis, treatment, and response assessment, putting it at the forefront of the next phase of personalized medicine. However, although exploratory studies demonstrate potential utility, there is a need for rigorous validation and standardization before AI can be utilized in clinical decision-making. In this review, we will provide a summary of the current literature implementing AI for outcome prediction in lung cancer. We will describe the anticipated impact of AI on the management of patients with lung cancer and discuss the challenges of clinical implementation of these techniques.
Regulation of 5α-Reductase Isoforms by Oxytocin in the Rat Ventral Prostate

Oxytocin(OT)ispresentinthemalereproductivetract,where it is known to modulate contractility, cell growth, and steroidogenesis. Little is known about how OT regulates these processes. This study describes the localization of OT receptor in the rat ventral prostate and investigates if OT regulates gene expression and/or activity of 5-reductase isoforms I and II. The ventral prostates of adult male Wistar rats were collected following daily sc administration of saline (control), OT, a specific OT antagonist or both OT plus antagonist for 3 d. Expression of the OT receptor was identified in the ventral prostate by RT-PCR and Western blot, and confirmed to be a single active binding site by radioreceptor assay. Immunohistochemistry localized the receptor to the epithelium of prostatic acini and to the stromal tissue. Real-time RT-PCR determined that OT treatment significantly reduced expressionof5-reductaseIbutsignificantlyincreased5-reductase II expression in the ventral prostate. Activity of both isoforms of5-reductasewassignificantlyincreasedbyOT,resultingin increased concentration of prostatic dihydrotestosterone. In conclusion, OT is involved in regulating conversion of testosteronetothebiologicallyactivedihydrotestosteroneintherat ventral prostate. It does so by differential regulation of 5reductase isoforms I and II. (Endocrinology 145: 5767–5773, 2004)
Comparison of parameter optimization methods for quantitative susceptibility mapping

Quantitative Susceptibility Mapping (QSM) is usually performed by minimizing a functional with data fidelity and regularization terms. A weighting parameter controls the balance between these terms. There is a need for techniques to find the proper balance that avoids artifact propagation and loss of details. Finding the point of maximum curvature in the L‐curve is a popular choice, although it is slow, often unreliable when using variational penalties, and has a tendency to yield overregularized results.
Photoprotection and Other Responses of Plants to High Light Stress

PHOTO PROTECTION 604 Prevention oj Excessive Light Absorption. 604 Removal of Excess Excitation Energy Directly within the Light-Capturing System . 604 Removal oj Active Oxygen Formed in the Photochemical Apparatus . 605 INACTIV A TIONiTURNOVER OF PS II 606 THE XANTHOPHYLL CYCLE AND THERMAL ENERGY DISSIPATION: A PHOTOPROTECTIVE RESPONSE 608 Characteristics oj the Xanthophyll Cycle . 608 Association Among the De-epoxidized State oj the Xanthophyll Cycle, Thermal Energy Dissipation. and Photoprotection . 609 Operation of the Xanthophyll Cycle in the Field . 611 CONCLUSIONS 618
Conditional Silencing of H-2Db Class I Molecule Expression Modulates the Protective and Pathogenic Kinetics of Virus-Antigen–Specific CD8 T Cell Responses during Theiler's Virus Infection

Key Points The floxed H-2Db mouse is a new tool for dissecting cell-specific Ag presentation. Rapid priming of CNS-infiltrating antiviral CD8 T cells requires DCs. LysM+ APCs are not equivalent to DCs in priming antiviral CD8 T cells. Theiler's murine encephalomyelitis virus (TMEV) infection of the CNS is cleared in C57BL/6 mice by a CD8 T cell response restricted by the MHC class I molecule H-2Db. The identity and function of the APC(s) involved in the priming of this T cell response is (are) poorly defined. To address this gap in knowledge, we developed an H-2Db LoxP-transgenic mouse system using otherwise MHC class I–deficient C57BL/6 mice, thereby conditionally ablating MHC class I–restricted Ag presentation in targeted APC subpopulations. We observed that CD11c+ APCs are critical for early priming of CD8 T cells against the immunodominant TMEV peptide VP2121-130. Loss of H-2Db on CD11c+ APCs mitigates the CD8 T cell response, preventing early viral clearance and immunopathology associated with CD8 T cell activity in the CNS. In contrast, animals with H-2Db–deficient LysM+ APCs retained early priming of Db:VP2121-130 epitope–specific CD8 T cells, although a modest reduction in immune cell entry into the CNS was observed. This work establishes a model enabling the critical dissection of H-2Db–restricted Ag presentation to CD8 T cells, revealing cell-specific and temporal features involved in the generation of CD8 T cell responses. Employing this novel system, we establish CD11c+ cells as pivotal to the establishment of acute antiviral CD8 T cell responses against the TMEV immunodominant epitope VP2121-130, with functional implications both for T cell–mediated viral control and immunopathology.
Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila

Promoter proximal pausing (PPP) of RNA polymerase II has emerged as a crucial rate-limiting step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT), and the negative elongation factor (NELF), which are highly conserved from Drosophila to humans. Here, we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhances Yki-driven growth, leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki in driving neoplastic growth. Interestingly, overexpression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily, and specifically, needed Yki overexpression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP—the ortholog of Yki in humans.
Outcomes of Maternal-Newborn Dyads After Maternal SARS-CoV-2

In this study, we describe perinatal morbidities among mothers with SARS-CoV-2 and their newborns. We also compare maternal-neonatal outcomes between symptomatic and asymptomatic mothers with SARS-CoV-2. BACKGROUND AND OBJECTIVES: Infection with a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. There are limited data describing the impact of SARS-CoV-2 infection on pregnant mothers and their newborns. The objective of this study is to describe characteristics and outcomes of maternal-newborn dyads with confirmed maternal SARS-CoV-2. METHODS: This was a multicenter, observational, descriptive cohort study with data collection from charts of maternal-newborn dyads who delivered at 4 major New York City metropolitan area hospitals between March 1 and May 10, 2020, with maternal SARS-CoV-2 infection. RESULTS: There were a total of 149 mothers with SARS-CoV-2 infection and 149 newborns analyzed (3 sets of twins; 3 stillbirths). Forty percent of these mothers were asymptomatic. Approximately 15% of symptomatic mothers required some form of respiratory support, and 8% required intubation. Eighteen newborns (12%) were admitted to the ICU. Fifteen (10%) were born preterm, and 5 (3%) required mechanical ventilation. Symptomatic mothers had more premature deliveries (16% vs 3%, P = .02), and their newborns were more likely to require intensive care (19% vs 2%, P = .001) than asymptomatic mothers. One newborn tested positive for SARS-CoV-2, which was considered a case of horizontal postnatal transmission. CONCLUSIONS: Although there was no distinct evidence of vertical transmission from mothers with SARS-CoV-2 to their newborns, we did observe perinatal morbidities among both mothers and newborns. Symptomatic mothers were more likely to experience premature delivery and their newborns to require intensive care.
PREDICTING MERCURY CONCENTRATION IN FISH USING MASS BALANCE MODELS

Mass balance models have frequently been used with laboratory-derived bioenergetic models to examine the accumulation of mercury (Hg) in fish. The accumulation of Hg in fish has usually been successfully described by these models. However, this has generally been achieved by adjusting the parameters of these models until there was a close fit between observed and predicted values. In this study, we present a simple Hg mass balance model (MMBM) to predict Hg concentration in fish. This MMBM was applied with three methods of estimating food consumption rates to predict Hg concentration in three freshwater fish species. The MMBM accurately predicted the accumulation of Hg in the three fish species examined in this study when it was combined with food consumption rates that were determined with a radioisotopic method. The MMBM tended to underestimate Hg concentration in fish when it was combined with food consumption rates determined using laboratory-derived bioenergetic models, possibly because activity cost.
Landscape of DNA binding signatures of myocyte enhancer factor-2B reveals a unique interplay of base and shape readout

Abstract Myocyte enhancer factor-2B (MEF2B) has the unique capability of binding to its DNA target sites with a degenerate motif, while still functioning as a gene-specific transcriptional regulator. Identifying its DNA targets is crucial given regulatory roles exerted by members of the MEF2 family and MEF2B’s involvement in B-cell lymphoma. Analyzing structural data and SELEX-seq experimental results, we deduced the DNA sequence and shape determinants of MEF2B target sites on a high-throughput basis in vitro for wild-type and mutant proteins. Quantitative modeling of MEF2B binding affinities and computational simulations exposed the DNA readout mechanisms of MEF2B. The resulting binding signature of MEF2B revealed distinct intricacies of DNA recognition compared to other transcription factors. MEF2B uses base readout at its half-sites combined with shape readout at the center of its degenerate motif, where A-tract polarity dictates nuances of binding. The predominant role of shape readout at the center of the core motif, with most contacts formed in the minor groove, differs from previously observed protein–DNA readout modes. MEF2B, therefore, represents a unique protein for studies of the role of DNA shape in achieving binding specificity. MEF2B–DNA recognition mechanisms are likely representative for other members of the MEF2 family.
The International Society of Renal Nutrition and Metabolism Commentary on the National Kidney Foundation and Academy of Nutrition and Dietetics KDOQI Clinical Practice Guideline for Nutrition in Chronic Kidney Disease.

The Academy of Nutrition and Dietetics and the National Kidney Foundation collaborated to provide an update to the Clinical Practice Guidelines (CPG) for nutrition in chronic kidney disease (CKD). These guidelines provide a valuable update to many aspects of the nutrition care process. They include changes in the recommendations for nutrition screening and assessment, macronutrients, and targets for electrolytes and minerals. The International Society of Renal Nutrition and Metabolism assembled a special review panel of experts and evaluated these recommendations prior to public review. As one of the highlights of the CPG, the recommended dietary protein intake range for patients with diabetic kidney disease is 0.6-0.8 g/kg/day, whereas for CKD patients without diabetes it is 0.55-0.6 g/kg/day. The International Society of Renal Nutrition and Metabolism endorses the CPG with the suggestion that clinicians may consider a more streamlined target of 0.6-0.8 g/kg/day, regardless of CKD etiology, while striving to achieve intakes closer to 0.6 g/kg/day. For implementation of these guidelines, it will be important that all stakeholders work to detect kidney disease early to ensure effective primary and secondary prevention. Once identified, patients should be referred to registered dietitians or the region-specific equivalent, for individualized medical nutrition therapy to slow the progression of CKD. As we turn our attention to the new CPG, we as the renal nutrition community should come together to strengthen the evidence base by standardizing outcomes, increasing collaboration, and funding well-designed observational studies and randomized controlled trials with nutritional and dietary interventions in patients with CKD.
How a catch - quota balancing system can go wrong: an evaluation of the species quota transformation provisions in the Icelandic multispecies demersal fishery

Pamela J. Woods1‡, Daniel S. Holland2, Guðrun Marteinsdottir3, and Andre E. Punt1 School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195, USA Northwest Fisheries Science Center, NMFS, NOAA, Seattle, WA 98192, USA MARICE, Faculty of Life and Environmental Sciences, University of Iceland, 101 Reykjavik, Iceland *Corresponding author: tel: +354 894 0342; fax: +354 525 4499; e-mail: pamelajwoods@gmail.com Present address: MARICE, Faculty of Life and Environmental Sciences, University of Iceland, 101 Reykjavik, Iceland.
Adaptation of balancing behaviour during continuous perturbations of stance. Supra-postural visual tasks and platform translation frequency modulate adaptation rate

When humans are administered continuous and predictable perturbations of stance, an adaptation period precedes the steady state of balancing behaviour. Little information is available on the modulation of adaptation by vision and perturbation frequency. Moreover, performance of supra-postural tasks may modulate adaptation in as yet unidentified ways. Our purpose was to identify differences in adaptation associated to distinct visual tasks and perturbation frequencies. Twenty non-disabled adult volunteers stood on a platform translating 10 cm in antero-posterior (AP) direction at low (LF, 0.18 Hz) and high frequency (HF, 0.56 Hz) with eyes open (EO) and closed (EC). Additional conditions were reading a text fixed to platform (EO-TP) and reading a text stationary on ground (EO-TG). Peak-to-peak (PP) displacement amplitude and AP position of head and pelvis markers were computed for each of 27 continuous perturbation cycles. The time constant and extent of head and pelvis adaptation and the cross-correlation coefficients between head and pelvis were compared across visual conditions and frequencies. Head and pelvis mean positions in space varied little across conditions and perturbation cycles but the mean head PP displacements changed over time. On average, at LF, the PP displacement of the head and pelvis increased progressively. Adaptation was rapid or ineffective with EO, but slower with EO-TG, EO-TP, EC. At HF, the head PP displacement amplitude decreased progressively with fast adaptation rates, while the pelvis adaptation was not apparent. The results show that visual tasks can modulate the adaptation rate, highlight the effect of the perturbation frequency on adaptation and provide evidence of priority assigned to pelvis stabilization over visual tasks at HF. The effects of perturbation frequency and optic flow and their interaction with other sensory inputs and cognitive tasks on the adaptation strategies should be investigated in impaired individuals and considered in the design of rehabilitation protocols.
Targeting the Synthetic Vulnerability of PTEN-Deficient Glioblastoma Cells with MCL1 Inhibitors

PTEN deletion or mutation occurs in 30% to 60% of patients with glioblastoma (GBM) and is associated with poor prognosis. Efficacious therapy for this subgroup of patients is currently lacking. To identify potential target(s) to selectively suppress PTEN-deficient GBM growth, we performed a three-step synthetic lethal screen on LN18 PTEN wild-type (WT) and knockout (KO) isogeneic GBM cell lines using a library containing 606 target-selective inhibitors. A MCL1 inhibitor UMI-77 identified in the screen exhibited excellent suppression on the proliferation, colony formation, 3D spheroid, and neurosphere formation of PTEN-deficient GBM cells. Mechanistically, loss of PTEN in GBM cells led to upregulation of MCL1 in posttranslational level via inhibition of GSK3β, and consequently confer cells resistance to apoptosis. Pharmacologic inhibition or knockdown of MCL1 blocked this PI3K–GSK3β–MCL1 axis and caused reduction of several antiapoptotic proteins, finally induced massive caspase-3 cleavage and apoptosis. In both subcutaneous and orthotopic GBM models, knockdown of MCL1 significantly impaired the in vivo growth of PTEN-deficient xenografts. Moreover, the combination of UMI-77 and temozolomide synergistically killed PTEN-deficient GBM cells. Collectively, our work identified MCL1 as a promising target for PTEN-deficient GBM. For future clinical investigations, priority should be given to the development of a selective MCL1 inhibitor with efficient brain delivery and minimal in vivo toxicity.
Prevalence, associated factors, and comorbidities of tinnitus in adolescents

The aim of this study was to investigate the prevalence of tinnitus among adolescents, and the factors known or hypothesized to be associated with tinnitus. Based on random sampling of school types and regions, a nationwide hearing survey of the first-year middle and high school students of South Korea was performed. The subjects underwent an otologic examination followed by pure tone audiometry up to 8 kHz. Questionnaires about the factors associated with hearing and tinnitus were completed by the students and their parents. Among the 1,593 subjects who completed the questionnaire and underwent pure tone audiometry, the prevalence of tinnitus was 46.0% and that of severe tinnitus was 9.1%. Tinnitus was associated with age, female gender, history of ear infection and sinusitis, leisure noise exposure due to karaoke and local-area-network gaming, alcohol consumption, and cigarette smoking. Noticeable hearing loss was not detected but participants with tinnitus complained of difficulty with sound localization, hearing in noise, and verbal working memory and were more susceptible to fatigue. The subjects with tinnitus also suffered more physical and mental health problems than did those without tinnitus. Thus, protection of the ears from noise and appropriate counseling should be considered for adolescents with tinnitus.
Selective Deficits in Contingency-Driven Ethanol Seeking Following Chronic Ethanol Exposure in Male Mice.

BACKGROUND People with alcohol use disorders exhibit an overreliance on habitual response strategies which may result from a history of chronic alcohol exposure. Although habits are defined by behavior that persists despite changes in outcome value and in action-outcome relationships, most research investigating the effects of ethanol exposure on habits has focused only on outcome devaluation. A clear understanding of the effects of chronic alcohol exposure on the ability to flexibly update behavior may provide insight into the behavioral deficits that characterize alcohol use disorders. METHODS To dissociate the effects of chronic intermittent ethanol (CIE) exposure on contingency-mediated sucrose versus ethanol seeking, adult male C57Bl/6J mice were assigned to two separate experiments. In the first experiment, mice were trained to self-administer ethanol prior to two cycles of interleaved CIE exposure by vapor inhalation. In a second experiment, mice were trained to self-administer sucrose and ethanol in separate training sessions prior to four cycles of interleaved CIE. The use of contingencies to mediate reward seeking was assessed using a contingency degradation paradigm. RESULTS In mice trained to self-administer only ethanol, two weeks of CIE resulted in escalated self-administration. At this time point, CIE-exposed mice, but not Air-exposed controls, exhibited ethanol seeking that was insensitive to changes in action-outcome contingency, consistent with habitual ethanol seeking. In mice trained to self-administer ethanol and sucrose rewards in sequential sessions, no escalation in self-administration across four weeks of CIE was observed. Under these conditions, neither Air- nor CIE-exposed mice reduced ethanol seeking in response to contingency degradation. In contrast, sucrose seeking remained goal-directed. CONCLUSIONS Our results suggest that chronic ethanol exposure impairs contingency-driven ethanol seeking more readily than sucrose-seeking behavior. Further, these findings indicate that the transition from contingency-mediated ethanol seeking occurs more rapidly than for sucrose seeking under similar ethanol exposure conditions.
Urology resident training in laparoscopic surgery – results of the first national survey in Poland

Introduction For many urological procedures the open approach is being replaced by the laparoscopic approach. Laparoscopy technique requires special training conditions. A well-designed, step-by step training program is significantly important for shortening the learning curve. Aim The purpose of the study was to evaluate urology residents’ (UR) experience in laparoscopic procedures, training patterns and facilities available in departments of urology in Poland. Material and methods The survey developed by the authors included 18 questions concerning laparoscopy training and was distributed among UR who participated in 2 courses in laparoscopic surgery for UR in Poland in 2017. The survey consisted of questions regarding the number of laparoscopic procedures, acquired laparoscopic experience, laparoscopic simulation training and motivation for further learning. Results Of the 2017 invited UR in Poland, 108 (34%) completed the survey. Seventy-two (78%) UR from the study group have access to laparoscopic surgery in their department. Only 20 (25%) of urology departments are equipped with a laparoscopy box and a small number of UR perform regular training. As a primary operator basic (varicocele repair) and advanced (e.g. radical nephrectomy, radical prostatectomy, nephron-sparing surgery) laparoscopic procedures are performed respectively by 55 (71%) UR and 8 (10%) UR. Most residents evaluated their laparoscopic skills as poor (15, 19%), very poor (31, 40%) or absent (10, 13%), while only 22 (28%) evaluated them as at least satisfactory. Conclusions Laparoscopic technique is available in most Polish training centers. However, the majority of UR consider their skills unsatisfactory. Additionally, a large number of Polish UR do not have access to intensive training. UR considered that their availability of training courses and fellowships is low. Surgical exposure among Polish UR comprises mainly minor laparoscopic procedures.