Miracle-dz/UniFAR-FTUs huggingface dataset:
Bidirectional and transactional relationships between parenting styles and child symptoms of ADHD, ODD, depression, and anxiety over 6 years

Abstract It is well established that mothers’ parenting impacts children's adjustment. However, much less is known about how children's psychopathology impacts their mothers’ parenting and how parenting and child symptoms relate either bidirectionally (i.e., a relationship in both directions over two time points) or transactionally (i.e., a process that unfolds over time) to one another over a span of several years. In addition, relatively little research addresses the role of fathers’ parenting in the development of children's symptoms and, conversely, how children may elicit certain types of parenting from fathers. In this study, data were collected from 491 families on mothers’ and fathers’ parenting styles (authoritarianism, authoritativeness, permissiveness, and overprotectiveness) and children's symptoms of psychopathology (attention deficit, oppositional defiant, depression, and anxiety) when children were age 3, 6, and 9 years old. Cross-lagged panel analyses revealed that parents and children affected one another in a bidirectional and transactional fashion over the course of the six years studied. Results suggest that children's symptoms may compound over time partially because they reduce exposure to adaptive and increase exposure to maladaptive parenting styles. Likewise, maladaptive parenting may persist over time due to the persistence of children's symptoms.
Transforming the Care of Patients with Diabetic Kidney Disease.

Diabetes and its associated complications pose an immediate threat to humankind. Diabetic kidney disease (DKD) is one of the most devastating complications, increasing the risk of death more than 10-fold over that in the general population [1]. Until very recently, the only drugs proven and recommended to slow progression of DKD were angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs), which act by inhibiting the renin-angiotensin system (RAS) [2]. Despite their efficacy as kidney and cardiovascular protective therapies and as antihypertensive agents, RAS inhibitors have been grossly underutilized [3]. Moreover, even when RAS inhibitors are used, patients still have a high residual risk of DKD progression [1, 2]. Finally, the kidney-protective effect of RAS inhibitors has been categorically demonstrated only in patients with macro-albuminuria included in the IDNT and RENAAL trials - not in other individuals [4]. The lack of new therapies to treat DKD over the past two decades has therefore represented a tremendous challenge for patients and health care providers alike. In recent years, a number of powerful new therapies have emerged that promise to transform care of patients with diabetes and kidney disease. The challenge to the community is to ensure rapid implementation of these treatments. This white paper highlights advances in treatment, opportunities for patients, challenges and possible solutions to advance kidney health and introduces the launch of the Diabetic Kidney Disease Collaborative at the American Society of Nephrology, to aid in accomplishing these goals.
Low-Density Lipoprotein Receptor Suppresses the Endogenous Cholesterol Synthesis Pathway To Oppose Gammaherpesvirus Replication in Primary Macrophages

LDL-R is a cell surface receptor that mediates the endocytosis of cholesterol-rich low-density lipoproteins, allowing cells to acquire cholesterol exogenously. Several RNA viruses usurp LDL-R function to facilitate replication; however, the role of LDL-R in DNA virus infection remains unknown. ABSTRACT Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections in >95% of adults worldwide and are associated with several cancers. We have shown that endogenous cholesterol synthesis supports gammaherpesvirus replication. However, the role of exogenous cholesterol exchange and signaling during infection remains poorly understood. Extracellular cholesterol is carried in the serum by several lipoproteins, including low-density lipoproteins (LDL). The LDL receptor (LDL-R) mediates the endocytosis of these cholesterol-rich LDL particles into the cell, thereby supplying the cell with cholesterol. We found that LDL-R expression attenuates gammaherpesvirus replication during the early stages of the replication cycle, as evident by increased viral gene expression in LDL-R−/− primary macrophages. This was not observed in primary fibroblasts, indicating that the antiviral effects of LDL-R are cell type specific. Increased viral gene expression in LDL-R−/− primary macrophages was due to increased activity of the endogenous cholesterol synthesis pathway. Intriguingly, despite type I interferon-driven increase in LDL-R mRNA levels in infected macrophages, protein levels of LDL-R continually decreased over the single cycle of viral replication. Thus, our study has uncovered an intriguing tug of war between the LDL-R-driven antiviral effect on cholesterol metabolism and the viral targeting of the LDL-R protein. IMPORTANCE LDL-R is a cell surface receptor that mediates the endocytosis of cholesterol-rich low-density lipoproteins, allowing cells to acquire cholesterol exogenously. Several RNA viruses usurp LDL-R function to facilitate replication; however, the role of LDL-R in DNA virus infection remains unknown. Gammaherpesviruses are double-stranded DNA viruses that are associated with several cancers. Here, we show that LDL-R attenuates gammaherpesvirus replication in primary macrophages by decreasing endogenous cholesterol synthesis activity, a pathway known to support gammaherpesvirus replication. In response, LDL-R protein levels are decreased in infected cells to mitigate the antiviral effects, revealing an intriguing tug of war between the virus and the host.
Electrophysiological characteristics of patients with nitrous oxide abuse

ABSTRACT Objective : In the young generations with nitrous oxide abuse (N2O), featured electrophysiological response of the peripheral neuropathy caused by nitrous oxide remains to be defined. Methods : Patients with nitrous oxide abuse (20 cases), two variants of Guillain-Barré syndrome (GBS), that is, acute inflammatory demyelinating polyradiculoneuropathy (GBS-AIDP, 19 cases) and acute motor axonal neuropathy (GBS-AMAN, 18 cases), as well as diabetic peripheral neuropathy (DPN, 20 cases) were enrolled into this study. Electrophysiological parameters including distal motor latency (DML), motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), amplitudes of compound muscle action potential (CMAP), and sensory nerve action potential (SNAP) were measured and analyzed by comparing the parameters between the aforementioned patients groups as well as normal control group (20 subjects). Results : Compared to normal control subjects, patients with nitrous oxide abuse showed prolonged DML, slower MNCV and SNCV in the limbs, lower amplitudes of CMAP in the median, tibial and peroneal nerves, and lower SNAP in median and ulnar nerves. Abnormalities of MNCV and amplitudes of CMAP in the lower limbs were significantly higher than that in the upper limbs . Abnormal electrophysiological features of patients with nitrous oxide abuse were dramatically different from those in GBS-AIDP or DPN patients, but similar to those in GBS-AMAN patients. Conclusions : Nitrous oxide abuse could cause abnormal electrophysiological response in the limbs. Some of the parameters (DML, MNCV, SNCV, CMAP and SNAP) appeared significantly different between the patients with nitrous oxide abuse, GBS with AIDP or AMAN, and DPN patients. Significance: Electrophysiological examination could be considered as an important supporting factor in differential diagnosis for nitrous oxide abuse, GBS with AIDP or AMAN, and DPN.
Potential G-quadruplexes and i-Motifs in the SARS-CoV-2

Quadruplex structures have been identified in a plethora of organisms where they play important functions in the regulation of molecular processes, and hence have been proposed as therapeutic targets for many diseases. In this paper we report the extensive bioinformatic analysis of the SARS-CoV-2 genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for SARS-CoV-2. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, 512 potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over seventeen thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were then compared subsequently to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire viral realm. Sequences found in common with other viral species were further analyzed and characterized. Sequences with high scores unique to the SARS-CoV-2 were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates were then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable therapeutic targets for the SARS-CoV-2.
Impact of climate change on Asiatic black bear (Ursus thibetanus) and its autumn diet in the northern highlands of Pakistan

Approximately 20%–30% of plant and animal species are at risk of extinction by the end of the 21st century owing to climate change. Range shifts and range contractions in plant species will dramatically affect the distribution of animals relying on them for food and shelter. The negative impacts of climate change on forested landscapes of the northern highlands of Pakistan (NHP) could change the species composition and distribution. The Asiatic black bear (Ursus thibetanus), a forest‐dwelling species, primarily depends on plants for foraging, and is assumed to be affected by climate change in NHP. Scat analyses and indigenous knowledge from Machiara National Park revealed the maximum consumption of Quercus species (natural food) and Zea mays (human grown food) by the Asiatic black bear in autumn season. We collected the occurrence data of the Asiatic black bear and its commonly used food (three Quercus spp.) in the NHP. We used the MaxEnt model to simulate current and future (in 2050 and 2070) distribution of the species under RCP4.5 (medium carbon emission scenario) and RCP8.5 (extreme carbon emission scenario). The results predict range reduction and extreme fragmentation in the habitats of all the Quercus spp. Besides, a dramatic decrease in the suitable (SH) and very highly suitable (HSH) habitats was predicted in the future. Range shift and range reduction of Quercus spp. may interrupt the denning chronology of Asiatic black bears, escalate the human‐black bear conflicts and local extirpation of the species. Given the extent and magnitude of climate change, it will likely not be enough to focus solely on the conservation of the Asiatic black bear. We need more dynamic planning aiming at mitigating the effect of climate change in forested landscapes including the Quercus forests.
The contribution of teledentistry in detecting tooth erosion in patients with eating disorders

Objective The aim of this study was to demonstrate that including a teledentistry consultation in the standard care provided to patients in an eating disorder day hospital could be beneficial, notably for screening for particular pathologies and preventing dental erosion. Methods We included 50 patients from the eating disorders unit of the University Hospital of Montpellier, all of whom underwent a dental examination using asynchronous telemedicine. We recorded the data using teledentistry software for the medical file and an intraoral camera for the clinical videos. Remote diagnosis was performed using the Basic Erosive Wear Examination index. In addition, the participants completed a questionnaire to assess their risk factors for dental pathologies. Results We found dental erosion in 92% of the patients, and 50% had at least one tooth with BEWE 2 or 3 type erosion. Conclusions Despite the fact that there can be wide variety within a group of individuals with similar risk factors, dental telemedicine could promote awareness within this at-risk population, as well as provide personalised prevention advice to each patient. Above all, it would make it possible to treat these patients' lesions at the earliest possible moment, thereby improving their outcomes.
A Comparison of Suicide Attempt Histories of Pediatric and Adult Medical Inpatients and Implications for Screening

Abstract Objective A suicide attempt is the most potent predictor of future suicidal behavior, yet little is known about how to manage and respond to reports of attempt histories in hospitalized medical patients. This study aims to describe the prevalence and characteristics of pediatric and adult medical inpatients who report a past suicide attempt. Method Participants were medical inpatients, aged 10–93 years, enrolled in two suicide risk screening instrument validation studies. Participants completed the Ask Suicide-Screening Questions (ASQ) and the Patient Health Questionnaire (PHQ). Results A total of 1324 medical inpatients (624 pediatric, 700 adult) completed the ASQ, with 114 participants (8.6%) reporting a past suicide attempt (51 pediatric; 63 adults). Comparing youth to adults, there was no significant difference between attempt rates (χ 2=0.29, p = 0.59). Youth with a past attempt were significantly more likely to report past week suicidal ideation (OR = 28.22; 95% CI = 5.90, 135.06) and have a history of mental health care (OR = 9.11; 95% CI = 2.59–32.10), compared to those without a past attempt. Adults with a past attempt were significantly more likely to screen positive for depression, compared to those without attempt histories (OR = 5.00; 95% CI = 2.31–10.83). Conclusions Nearly 9% of hospitalized medical patients endorsed a past suicide attempt when screened. Since adolescence is a critical time for detecting suicide risk, screening that includes past suicidal behavior may be an important means to identify youth with recent suicidal thoughts. By assessing recency of suicide attempts in adults, medical settings may optimize the effectiveness of how positive suicide risk screens are managed. HIGHLIGHTS Roughly 9% of medical patients reported a past suicide attempt when screened. Adolescence is a critical time for detecting suicide risk and intervening. Assessing past suicide attempts in adults can help with managing positive screens.
Light, power, action! Interaction of respiratory energy and blue light induced stomatal movements.

Although the signalling pathway of blue light dependent stomatal opening is well characterized, little is known about the interspecific diversity, the role it plays in the regulation of gas exchange and the source of energy used to drive the commonly observed increase in pore aperture. Using a combination of red and blue light under ambient and low [O2 ] (to inhibit respiration), the interaction between blue light, photosynthesis and respiration in determining stomatal conductance was investigated. These findings were used to develop a novel model to predict the feedback between photosynthesis and stomatal conductance under these conditions. Here we demonstrate that blue light induced stomatal responses are far from universal, and that significant species-specific differences exist both in term of rapidity and magnitude. Increased stomatal conductance under blue light reduced photosynthetic limitation, at the expense of water loss. Moreover, we stress the importance of the synergistic effect of blue light and respiration in driving rapid stomatal movements especially when photosynthesis is limited. These observations will help re-shape our understanding of diurnal gas exchange in order to exploit the dynamic coordination between A and gs , as a target for enhancing crop performance and water use efficiency.
Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study)

PURPOSE To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. PATIENTS AND METHODS Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. RESULTS Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively (P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively (P = .15). CONCLUSION In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.
Exercise reduces circulating biomarkers of cellular senescence in humans

Cellular senescence has emerged as a significant and potentially tractable mechanism of aging and multiple aging‐related conditions. Biomarkers of senescent cell burden, including molecular signals in circulating immune cells and the abundance of circulating senescence‐related proteins, have been associated with chronological age and clinical parameters of biological age in humans. The extent to which senescence biomarkers are affected by interventions that enhance health and function has not yet been examined. Here, we report that a 12‐week structured exercise program drives significant improvements in several performance‐based and self‐reported measures of physical function in older adults. Impressively, the expression of key markers of the senescence program, including p16, p21, cGAS, and TNFα, were significantly lowered in CD3+ T cells in response to the intervention, as were the circulating concentrations of multiple senescence‐related proteins. Moreover, partial least squares discriminant analysis showed levels of senescence‐related proteins at baseline were predictive of changes in physical function in response to the exercise intervention. Our study provides first‐in‐human evidence that biomarkers of senescent cell burden are significantly lowered by a structured exercise program and predictive of the adaptive response to exercise.
Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial

Background In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)—mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR). Methods A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1. 1 modified for immune-based therapeutics. Results Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1–2. Conclusion Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR. Trial registration numbers ANZGOG1601, ACTRN12617000106336, and NCT03015129.
Motion estimation and correction in SPECT, PET and CT

Patient motion impacts single photon emission computed tomography (SPECT), positron emission tomography (PET) and x-ray computed tomography (CT) by giving rise to projection data inconsistencies that can manifest as reconstruction artifacts, thereby degrading image quality and compromising accurate image interpretation and quantification. Methods to estimate and correct for patient motion in SPECT, PET and CT have attracted considerable research effort over several decades. The aims of this effort have been two-fold: to estimate relevant motion fields characterizing the various forms of voluntary and involuntary motion; and to apply these motion fields within a modified reconstruction framework to obtain motion-corrected images. The aims of this review are to outline the motion problem in medical imaging and to critically review published methods for estimating and correcting for the relevant motion fields in clinical and preclinical SPECT, PET and CT. Despite many similarities in how motion is handled between these modalities, utility and applications vary based on differences in temporal and spatial resolution. Technical feasibility has been demonstrated in each modality for both rigid and non-rigid motion but clinical feasibility remains an important target. There is considerable scope for further developments in motion estimation and correction, and particularly in data-driven methods that will aid clinical utility. State-of-the-art deep learning methods may have a unique role to play in this context.