Miracle-dz/UniFAR-FTUs huggingface dataset:
UNIFORM-IN-SUBMODEL BOUNDS FOR LINEAR REGRESSION IN A MODEL-FREE FRAMEWORK

For the last two decades, high-dimensional data and methods have proliferated throughout the literature. Yet, the classical technique of linear regression has not lost its usefulness in applications. In fact, many high-dimensional estimation techniques can be seen as variable selection that leads to a smaller set of variables (a “submodel”) where classical linear regression applies. We analyze linear regression estimators resulting from model selection by proving estimation error and linear representation bounds uniformly over sets of submodels. Based on deterministic inequalities, our results provide “good” rates when applied to both independent and dependent data. These results are useful in meaningfully interpreting the linear regression estimator obtained after exploring and reducing the variables and also in justifying post-model-selection inference. All results are derived under no model assumptions and are nonasymptotic in nature.
Single step synthesized sulfur and nitrogen doped carbon nanodots from whey protein: nanoprobes for longterm cell tracking crossing the barrier of photo-toxicity

Long-term cell tracking is a research interest for biological scientists across disciplines and applications. However, long-term cell tracking experiments are often limited due to photobleaching and phototoxicity. In the current study, a carbonaceous nanoprobe was developed using a single step microwave assisted degradation of whey protein in the aqueous phase. The CNDs were characterized via UV-Vis spectroscopy, fluorescence spectroscopy, HRTEM, DLS and FTIR. Due to choice of the precursor, the CNDs were observed to be doped with sulfur and nitrogen. The CNDs were capable of bioimaging. In a 2D cell culture system (culture flask), the cells retained fluorescence for up to five passages. In a 3D microenvironment, cell tracking was also successful for up to 10 days. The CNDs were observed to be capable of scavenging superoxides and hydroxyl radicals in vitro. The CNDs were also observed to save cells from phototoxicity and UV exposure via cytotoxicity, microscopy and nanoindentation analysis.
Differences in Switching Away From Smoking Among Adult Smokers Using JUUL Products in Regions With Different Maximum Nicotine Concentrations: North America and the United Kingdom

Abstract Introduction Electronic nicotine delivery systems (ENDS) may improve public health if they facilitate smokers switching away from cigarettes. Conceptually, switching is facilitated when ENDS provide adequate nicotine delivery. Switching rates among smokers who purchased the JUUL System (“JUUL”) were compared in the United Kingdom (UK), where regulations limit nicotine concentration to 20 mg/mL versus North America (N.Am.; United States and Canada), where higher concentrations are available. Aims and Methods Adult established smokers (age ≥21, smoked ≥100 cigarettes, smoking some days or every day at baseline) who newly purchased JUUL were recruited into a longitudinal study (UK: N = 1247; N.Am.: N = 8835). Complete switching (no smoking for ≥30 days) was assessed 1, 3, and 6 months after purchase; propensity score matching (PSM) and logistic regression compared switching after adjusting for baseline characteristics. Results In both N.Am. and UK, ≥82% of participants reported using the highest JUUL nicotine concentration available (UK: 18 mg/mL; N.Am.: 59 mg/mL). Unadjusted switching rates did not differ at 1 month (17%–18%); unadjusted and adjusted rates were significantly higher in N.Am. (vs. UK) at 3 and 6 months. In the PSM sample, after additional covariate adjustment, rates were significantly higher in N.Am. (vs. UK) at 3 months (31.5% vs. 22.7%; odds ratio [95% confidence interval, CI] = 1.59 [1.25, 2.02]) and 6 months (38.0% vs. 26.0%; odds ratio [95% CI] = 1.79 [1.37, 2.35]). Conclusions These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Differences in smoking and ENDS use characteristics did not explain associations of location and switching; however, between-country differences may be affected by unmeasured factors. Implications Switching rates were lower among smokers who purchased the JUUL System (“JUUL”) in the UK, where regulations limit nicotine concentration to 20 mg/mL versus N.Am. (United States and Canada), where higher concentrations are available—before and after controlling for differences in smoking and ENDS use characteristics. These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Between-country differences may be affected by unmeasured factors; future research should consider these factors and the extent to which regulatory policy environments may explain differences in switching among adult smokers.
Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review

Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant to radiation. The biological response to radiobiological hypoxia is one of few physiologically relevant stresses that activates both the unfolded protein and DNA damage responses (UPR and DDR). Links between these pathways have been identified in studies carried out in normoxia. Based in part on these previous studies and recent work from our laboratory, we hypothesised that the biological response to hypoxia likely includes overlap between the DDR and UPR. While inhibition of the DDR is a recognised strategy for improving radiation response, the possibility of achieving this through targeting the UPR has not been realised. We carried out a systematic review to identify links between the DDR and UPR, in human cell lines exposed to <2% O2. Following PRISMA guidance, literature from January 2010 to October 2020 were retrieved via Ovid MEDLINE and evaluated. A total of 202 studies were included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 and SP1 were highlighted as potential links between the hypoxic DDR and UPR. Overall, we identified very few studies which demonstrate a molecular link between the DDR and UPR in hypoxia, however, it is clear that many of the molecules highlighted warrant further investigation under radiobiological hypoxia as these may include novel therapeutic targets to improve radiotherapy response.
Clinical, biological, and molecular genetic features of Richter syndrome and prognostic significance: A study of the French Innovative Leukemia Organization

To Editor: Richter syndrome is the transformation of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma into aggressive lymphoma. This study focuses on the diffuse large B-cell lymphoma (DLBCL) variant of Richter syndrome (RS). Richter syndrome prognosis is poor, with a median overall survival (OS) ranging from 4 months to 2 years. 1 In 80%-90% of cases, the RS clone arises from the CLL clone, whereas a minority of RS are clonally unrelated DLBCLs in a patient with CLL. The latter is associated with a median OS similar to de novo DLBCL. Two clinico-biological prognostic scoring systems are currently available. 2,3 Richter syndrome molecular profile shares only a few common features with de novo DLBCLs, with four highly preva-lent genomic abnormalities: TP53 abnormalities, MYC deregulations, NOTCH1 mutations and CDKN2A/B deletions. Richter syndrome har-bors an unmutated IGHV in 80% of cases and a high prevalence of stereotypic B-Cell Receptor (BCR). 1 To date, only a few RS molecular abnormalities were investigated for prognostic value. Our objectives clinical RS
Neurological side effects of COVID‐19 vaccines are rare

and Phase 3 trials. The Advisory Committee on Immunization Practices (ACIP) of the CDC also presented similar data compared to the unvaccinated group. No statistical signals were detected for Bell's palsy, convul-sions/seizures, hemorrhagic or ischemic stroke, and venous thromboembolism. 7 Despite the limitation of neurological adverse events reporting, public media showed a few cases of people with continu-ous trunk movements and limbs or walking difficulties. 8 These reports were considered mainly as functional neurological disorders. The causality between these symptoms and vaccination was uncertain. Based on the current evidence, though more neurological adverse effects were reported with the massive worldwide vaccination, the causality is yet to be confirmed. As the vaccinated population in-creases, inevitable more neurological incidents will be seen. The link between them and the vaccine association will need to be tested by comparing their incidence rate with epidemiological data preceding the pandemic. We agree that it is essential to establish a transpar-ent and efficient reporting system of vaccination safety. This will re-quire full collaboration between regulators, healthcare workers, the industry, and the general public. by from
Not a matter of shape: The influence of tool characteristics on electrodermal activity in response to haptic exploration of Lower Palaeolithic tools

Haptics involves somatosensory perception through the skin surface and dynamic touch based on the proprioceptive response of the whole body. Handling Palaeolithic stone tools influences the arousal and attentional engagement, which can be detected and measured through electrodermal activity. Although tool shape has generally been studied to consider tool functions or tool making, it is also a major factor in tool sensing and haptic perception. The purpose of this survey is to analyze whether the electrodermal reactions are influenced by stone tool morphology.
Distal Femur Replacement Versus Open Reduction and Internal Fixation for Treatment of Periprosthetic Distal Femur Fractures: A Systematic Review and Meta-Analysis

Supplemental Digital Content is Available in the Text. Objective: To compare complications and functional outcomes of treatment with primary distal femoral replacement (DFR) versus open reduction and internal fixation (ORIF). Data Sources: PubMed, Embase, and Cochrane databases were searched for English language studies up to May 19, 2020, identifying 913 studies. Study Selection: Studies that assessed complications of periprosthetic distal femur fractures with primary DFR or ORIF were included. Studies with sample size ≤5, mean age <55, nontraumatic indications for DFR, ORIF with nonlocking plates, native distal femoral fractures, or revision surgeries were excluded. Selection adhered to the PRISMA criteria. Data Extraction: Study quality was assessed using previously reported criteria. There were 40 Level IV studies, 17 Level III studies, and 1 Level II study. Data Synthesis: Fifty-eight studies with 1484 patients were included in the meta-analysis. Complications assessed {incidence rate ratio [IRR] [95% confidence interval (CI)]: 0.78 [0.59–1.03]} and reoperation or revision [IRR (95% CI): 0.71 (0.49–1.04)] were similar between the DFR and ORIF cohorts. The mean knee range of motion was greater in the ORIF cohort (DFR: 90.47 vs. ORIF: 100.36, P < 0.05). The mean Knee Society Score (KSS) (DFR: 79.41 vs. ORIF: 82.07, P = 0.35) and return to preoperative ambulatory status were similar [IRR (95% CI): 0.82 (0.48–1.41)]. Conclusions: In comparing complications among patients treated for periprosthetic distal femur fracture with DFR or ORIF, there was no difference between the groups. There were also no differences in functional outcomes, although knee range of motion was greater in the ORIF group. This systematic review and meta-analysis highlights the need for future prospective trials evaluating the outcomes of these divergent treatment strategies. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Sex Differentiation in Amphibians: Effect of Temperature and Its Influence on Sex Reversal

The role of environmental factors in sexual differentiation in amphibians is not new. The effect of hormones or hormone-like compounds is widely demonstrated. However, the effect of temperature has traditionally been regarded as something anecdotal that occurs in extreme situations and not as a factor to be considered. The data currently available reveal a different situation. Sexual differentiation in some amphibian species can be altered even by small changes in temperature. On the other hand, although not proven, it is possible that temperature is related to the appearance of sex-reversed individuals in natural populations under conditions unrelated to environmental contaminants. According to this, temperature, through sex reversal (phenotypic sex opposed to genetic sex), could play an important role in the turnover of sex-determining genes and in the maintenance of homomorphic sex chromosomes in this group. Accordingly, and given the expected increase in global temperatures, growth and sexual differentiation in amphibians could easily be affected, altering the sex ratio in natural populations and posing major conservation challenges for a group in worldwide decline. It is therefore particularly urgent to understand the mechanism by which temperature affects sexual differentiation in amphibians.
Outcome and safety analysis of endometrial cancer patients treated with postoperative 3D-conformal radiotherapy or intensity modulated radiotherapy

Abstract Background We sought to analyze the toxicity rates and the treatment outcomes in endometrial cancer (EC) patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). Material and methods The clinical data of 646 EC patients treated with postoperative adjuvant 3DCRT (265 patients, 41%) or with IMRT (381 patients, 59%) between April 2007 and August 2019 were retrospectively analyzed. The primary endpoints were treatment-related acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary endpoints were LC and overall survival (OS) and disease-free survival (DFS). Results Median follow-up time was 37 months. The rates for acute GI and GU toxicities of any grade for the entire group were 55.6% and 46.8%, respectively. Acute grade ≥2 GI toxicity was significantly less in patients treated with IMRT compared to those treated with 3DCRT (11.0% vs. 19.2%, p=.004). However, no significant difference grade ≥2 GU toxicities was observed between the 3DCRT and IMRT groups (15.1% vs. 11.0%; p=.15). Acute grade ≥2 GI and GU toxicities were higher in patients receiving systemic chemotherapy, while paraaortic field irradiation increases only the risk of acute grade ≥2 GI toxicity. Estimated 3-year late grade ≥3 GI toxicity rates in the 3DCRT- and IMRT-treated patients were 4.6% and 1.9% (p= .03), respectively. The patients treated with adjuvant ChT had higher rates of late serious GI complications than those without adjuvant ChT. No significant difference in terms of survival and disease control was observed between the 3DCRT and IMRT treatment groups. No significant factor for LC was found in the multivariate analysis. Conclusion In this multicentric study involving one of largest patient population, we found that IMRT-treated EC patients showed comparable clinical outcomes but with a lower incidence of GI toxicities compared with those treated with 3DCRT.
Food Security Status among U.S. Older Adults: Functional Limitations Matter

Abstract This study aimed to assess the relationship between food security and health outcomes among older adults (age 65+) in the U.S. We used a pooled sample (2011–2015, N = 37,292) from the National Health Interview Survey (NHIS) and ordered logit models to assess characteristics associated with food security including health conditions (diabetes and hypertension) and functional activity limitations. We estimated that 1.3 million individuals aged 65+ in the U.S. had low/very low food security. Having at least one functional limitation (OR = 1.717, 95% CI = 1.436, 2.054) was significantly associated with low/very low food security. Having fair or poor health status (OR = 3.315, 95% CI = 2.938, 3.739) was also a significant factor for food security among older adults, while having health insurance coverage (OR = 0.467, 95% CI = 0.341, 0.64) was negatively associated with food insecurity. Demographics and socioeconomic characteristics were significantly related to food insecurity among seniors. Seniors with functional limitations and poor health status are at risk for food insecurity. Interventions at the clinical site of care may be useful in addressing food security issues for older adults.
Leptomeningeal metastasis from cervical cancer: Report of two cases and a review of the literature

Leptomeningeal metastases from cervical cancer are extremely rare, with only 24 cases reported in the English‐language literature. Leptomeningeal metastasis (LM) is usually a late event, but it can develop at any stage. A 44‐year‐old woman presented with vertigo, tinnitus, diminution of hearing, and a cervical tumor at the initial visit. She underwent whole brain radiotherapy and systemic chemotherapy. Five months after the initial visit, her condition deteriorated rapidly and she died. A 49‐year‐old woman underwent surgery and pelvic radiotherapy for cervical cancer. She underwent resection of lung metastases 2 years later and received systemic chemotherapy for lymph node metastases 4 years later. Five years after the initial visit, the patient suddenly presented with diplopia, headache, and vomiting; her clinical course was fulminant and she died. Most patients with LM present with diverse clinical manifestations and deteriorate rapidly despite multiple treatment modalities. Gynecologic oncologists should be aware of this rare complication.
Culture shapes emotion perception from faces and voices: changes over development

ABSTRACT The perception of multisensory emotion cues is affected by culture. For example, East Asians rely more on vocal, as compared to facial, affective cues compared to Westerners. However, it is unknown whether these cultural differences exist in childhood, and if not, which processing style is exhibited in children. The present study tested East Asian and Western children, as well as adults from both cultural backgrounds, to probe cross-cultural similarities and differences at different ages, and to establish the weighting of each modality at different ages. Participants were simultaneously shown a face and a voice expressing either congruent or incongruent emotions, and were asked to judge whether the person was happy or angry. Replicating previous research, East Asian adults relied more on vocal cues than did Western adults. Young children from both cultural groups, however, behaved like Western adults, relying primarily on visual information. The proportion of responses based on vocal cues increased with age in East Asian, but not Western, participants. These results suggest that culture is an important factor in developmental changes in the perception of facial and vocal affective information.
Glycemic Variability With Insulin Glargine Versus Detemir in Hospitalized Patients With Diabetes

Background: Prior research has demonstrated increased mortality with increasing glycemic variability (GV) in hospitalized patients with diabetes. Objective: We aimed to compare glycemic variability (GV) of insulin glargine to detemir in the inpatient setting. Methods: This single-center, retrospective, cohort study evaluated noncritically ill patients with diabetes on long-acting insulin at a large academic medical institution between 2010 and 2017. This study was reviewed and approved by the Institutional Review Board. The formulary transitioned from insulin glargine to detemir in December 2013; therefore, patients were compared before and after transition. The primary endpoint was to compare coefficient of variation (CV), a measure of GV, between detemir and glargine. Secondary endpoints included GV measured by standard deviation (SD), CV within 72 hours of long-acting insulin initiation, length-of-stay (LOS), in-hospital mortality, and comparison between subgroups. Results: 2334 patients were included in the study, and there were 1167 in each group. CV was significantly less variable with detemir compared to glargine (33.7% versus 34.8%, difference = 1.09, p = 0.02) and remained significant after controlling for confounders. Similarly, SD was significantly less with detemir (p = 0.048). CV within 72 hours, LOS, and in-hospital mortality were not statistically different. Lastly, GV was higher in medical patients compared to surgical. Conclusion: Insulin detemir exhibited less GV than insulin glargine, although the small difference is unlikely to be clinically significant. Application of this data will aid in formulary decisions and support the use of either agent within the hospital setting.
Out of the shadow of interleukin-17A: the role of interleukin-17F and other interleukin-17 family cytokines in spondyloarthritis

Purpose of review The last decade has witnessed tremendous advances in revealing an important role for the interleukin (IL)-17 cytokine family in the pathogenesis of spondyloarthritis (SpA). Although most attention has been focused on IL-17A, a potential role of other IL-17 family members in inflammation and tissue remodelling is emerging. Herein, I review recent studies covering the role of IL-17B-F cytokines in the pathogenesis of SpA. Recent findings Several recent studies provided new insights into the cellular source, regulation and function of IL-17F. IL-17F/IL-17A expression ratio is higher in psoriatic skin compared to SpA synovitis. IL-17F-expressing T cells produce different proinflammatory mediators than IL-17A-expressing cells, and IL-17F and IL-17A signal through different receptor complex. Dual IL-17A and IL-17F neutralization resulted in greater suppression of downstream inflammatory and tissue remodelling responses. Furthermore, there is additional evidence of IL-23-independent IL-17 production. In contrast to IL-17A, IL-17F and IL-17C, which play proinflammatory roles in skin and joint inflammation, an anti-inflammatory function is proposed for IL-17D. An increase in IL-17E is associated with subclinical gut microbiome alterations after anti-IL-17A therapy in SpA patients. Summary IL-17 family cytokines may act as agonists or antagonists to IL-17A contributing in concert to local inflammatory responses. Understanding their function and identifying their cellular sources, and molecular mechanisms driving their expression will be the key to designing rational therapies in SpA.
Bariatric surgery and the liver—Mechanisms, benefits, and risks

The prevalence of obesity and metabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) has risen dramatically over the past decades. At present, bariatric surgery is the most effective treatment for this global health problem, through effects on food intake, gut hormone secretion, metabolic signaling pathways, and adipose tissue dysfunction. The liver occupies a central role in carbohydrate, protein, and lipid metabolism. Notably, a reduction in hepatic fat content and an improvement in hepatic insulin resistance are among the earliest beneficial effects of bariatric surgery, which has therefore emerged as an attractive treatment option for NAFLD. However, as the scope and popularity of weight loss surgery have expanded, new questions have arisen regarding its safety in patients with liver cirrhosis, the outcome of liver transplantation in patients with a history of bariatric surgery, and over incidental reports of liver failure following surgery. Studies in humans and rodents have also linked bariatric surgery to an increased risk of developing alcohol use disorder, a major risk factor for liver disease. This review integrates data from clinical and translational research to delineate both the beneficial impact of bariatric surgery on the liver and the potential risks involved.