Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency of Expression of PD-1 and PD-L1 In Head And Neck Squamous Cell Carcinoma And their Association With Nodal Metastasis: A Cross-Sectional Study

Objective: The objective of this study was to determine the Immunohistochemical expression of PD- 1, PD-L1 and its association with nodal metastasis in head and neck squamous cell carcinoma. Materials and Methods: A total of 66 cases were studied at Oral pathology/Histopathology, Armed forces Institute of Pathology (AFIP), Rawalpindi. The tissue sampling and processing yielded the formalin fixed, paraffin wax blocks. These blocks were cut into the thin sections (5 microns) by the microtome and then were mounted on the glass slides. This was followed by the routine H&E staining and then IHC staining (PD-1 and PD-L1) of these tissues mounted slides. For each case a definitive histological diagnosis was made. The two types of variables were analyzed. For qualitative variables frequencies and percentages were calculated whereas for quantitative variables means and standard deviations were analyzed. The Chi-square test then was applied to evaluate the significant difference and p-value of ≤0.05 was taken significant. Results: This study was conducted at Histology department, Armed Forces Institute of Pathology, Rawalpindi over a period of one year from June 2019 to June 2020. It revealed male and female patients with 66.7% (44 Cases) and 33.3% (22cases) percentages respectively. The mean age was found to be 59.53 ± 13.637 (mean ± SD) and the mandible (37.9%) was the most commonly affected site. In total of 66 cases, 48 (72.7%) cases with metastasis of lymph nodes were presented. Out of 66 cases ,47 (71.2%) cases showed positive expression of PD-1 in the TILs seen among the primary tumor of the specimens, whereas, 40 (60.6%) cases showed positive PD-L1 expression in tumor cells of primary tumor.In comparison, as out of 66 cases ,48 (72.5%) cases showed lymph nodes metastasis, out of which 45 showed positive expression for PD-1 and 25 out of those 48 cases showed positive expression for PD-L1 in metastatic lymph nodes.The p-value turned to be significant for PD-1 IHC expression and PD-L1 IHC expression in the primary tumorand metastatic lymph nodes. Conclusion: A significant correlation was inferred among IHC expression of PD-1 and PD-L1 with lymph nodes metastasis. Accurate evaluation, analysis and precise management with aid of IHC markers results in initial and timely diagnosis and favorable treatment outcomes helping in the evaluation of disease course at preliminary diagnosis on incisional biopsies.
Spam and Criminal Activity

The rapid growth of the internet is transforming how we engage and communicate. It also creates new opportunities for fraud and data theft. One way cybercriminals exploit the vulnerabilities of new technologies and potential victims is the use of deceptive emails on a massive scale. In a sample of more than 13 million emails identified as spam, more than 100,000 contained malicious attachments; nearly 1.4 million contained malicious web links. If opened, these attachments and links could infect the recipients’ devices with software that allows cybercriminals to remotely access them. This paper describes how crime groups increasingly adopt novel approaches to cybercrime. Increased law enforcement capacity, the cultivation of high-level coordination between industry, government and police, and the further development of machine learning techniques should be at the forefront of government initiatives in this area.
Evaluation of Intravenous Push Piperacillin-Tazobactam on Time to Antibiotic Administration in Emergency Department Patients with Sepsis

Purpose: The purpose of this study was to determine if intravenous push (IVP) administration of piperacillin-tazobactam reduced the time to antibiotic administration compared to intravenous piggyback (IVPB) in emergency department (ED) patients who present with sepsis. Methods: This was a retrospective cohort study of patients with sepsis who received piperacillin-tazobactam before and after implementation of an IVPB to IVP conversion protocol. Results: A total of 486 charts were reviewed and the final analysis included 127 patients in each group. The mean time to administration of piperacillin-tazobactam was 67 (± 48) minutes and 58 (± 36) minutes in the IVPB and IVP cohorts, respectively (P = NS). The time to administration of secondary antibiotics was reduced by 38 minutes in patients who received piperacillin-tazobactam by IVP (105 min ±69 vs 67 min ±37; P < .001). Nurse administration time was reduced by 11 min for piperacillin-tazobactam (54 min ±46 vs 43 min ±33; P = .034) and 40 min for secondary antibiotics (90 min ±67 vs 50 min ±32; P = < .001) in the IVP group. There was no difference in hypersensitivity reactions, hospital length of stay, or mortality. Conclusion: Conversion from piperacillin-tazobactam IVPB to IVP was associated with a reduction in time to piperacillin-tazobactam and secondary antibiotic administration in emergency department patients with sepsis. Further prospective research is needed to evaluate clinical outcomes associated with IVP administration.
Efficacy and Safety of a New Sustained-release Pregabalin Formulation Compared With Immediate-release Pregabalin in Patients With Peripheral Neuropathic Pain

Objective: This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients. Materials and Methods: This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores. Results: A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval −0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (−0.78; P noninferiority<0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred. Discussion: The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.
Interactions between microorganisms and marine microplastics: A call for research

Synthetic thermoplastics constitute the majority by percentage of anthropogenic debris entering the Earth's oceans. Microplastics (=5-mm fragments) are rapidly emerging pollutants in marine ecosystems that may transport potentially toxic chemicals into macrobial food webs. This commentary evaluates our knowledge concerning the interactions between marine organisms and microplastics and identifies the lack of microbial research into microplastic contamination as a significant knowledge gap. Microorganisms (bacteria, archaea, and picoeukaryotes) in coastal sediments represent a key category of life with reference to understanding and mitigating the potential adverse effects of microplastics due to their role as drivers of the global functioning of the marine biosphere and as putative mediators of the biodegradation of plastic-associated additives, contaminants, or even the plastics themselves. As such, research into the formation, structure, and activities of microplastic-associated microbial biofilms is essential in order to underpin management decisions aimed at safeguarding the ecological integrity of our seas and oceans.
Association of the methylenetetrahydrofolate reductase (MTHFR) gene variant C677T with serum homocysteine levels and the severity of ischaemic stroke: a case–control study in the southwest of China

Objective To determine whether the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism is linked to the risk of ischaemic stroke and circulating homocysteine (Hcy) levels in a Chinese population. Methods This case–control study recruited angiogram-diagnosed patients with ischaemic stroke and healthy control subjects. The plasma Hcy concentrations were measured and the MTHFR C677T gene polymorphism was genotyped. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of the ischaemic stroke. Results This study recruited 198 patients with ischaemic stroke and 168 controls. The TT genotype conferred a higher risk for ischaemic stroke than the CC genotype (odds ratio of 3.563; 95% confidence interval [CI] 1.412, 4.350). The T allele was the predisposing allele for ischaemic stroke. Hcy had an area under the receiver operating characteristic (ROC) curve of 0.624 (95% CI 0.530, 0.758). The ROC for Hcy demonstrated its usefulness in predicting ischaemic stroke. Hcy levels were not associated with ischaemic stroke severity as measured by the NIHSS. Conclusion The MTHFR C677T gene polymorphism affects circulating Hcy levels. The MTHFR C677T gene polymorphism and hyperhomocysteinaemia may play important roles in predicting the risk of ischaemic stroke.
Rapid molecular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in hospital employees with mild, nonspecific respiratory symptoms facilitates expedient return to work

Abstract Nonspecific respiratory symptoms overlap with coronavirus disease 2019 (COVID-19). Prompt diagnosis of COVID-19 in hospital employees is crucial to prevent nosocomial transmission. Rapid molecular SARS-CoV-2 testing was performed for 115 symptomatic employees. The case positivity rate was 2.6%. Employees with negative tests returned to work after 80 (±28) minutes.
Association between placental global DNA methylation and blood pressure during human pregnancy

Objective: Gene-specific placental DNA methylation patterns differ between normal pregnancies and pregnancies complicated by hypertension. However, whether global placental DNA methylation is associated with maternal blood pressure remains controversial. Methods: Using multiple linear regression models, we analysed the association between maternal mean arterial pressure (MAP) at the third trimester of pregnancy and global DNA methylation in the placenta in 922 mothers using LC-ESI-MS/MS. To better characterize the contribution of genetic or epigenetic mechanisms, we performed isolated analyses in mothers with and without a family history of hypertension. Results: Mean placental global DNA methylation was 3.00 ± 0.46%. A significant negative correlation between placental global DNA methylation and mean arterial blood pressure (MAP) in the third trimester could be observed (P = 0.023, r = -0.075). This association remained significant after adjusting for confounders. In placenta samples from mothers with a family history of hypertension, mean maternal MAP was higher (86.1 ± 8.1 vs. 84.6 ± 7.5, P < 0.01) and placental global DNA methylation was lower (2.94 ± 0.43 vs. 3.04 ± 0.47, P < 0.01) compared with samples without a family history of hypertension. Furthermore, the significant independent negative correlation between global placental DNA methylation and MAP was only found in mothers without a family history of hypertension. Conclusion: This study showed an independent negative correlation between placental global DNA methylation and maternal MAP in mothers without a family history of hypertension.
A transposon‐introduced G‐quadruplex motif is selectively retained and constrained to downregulate CYP321A1

Insects utilize xenobiotic compounds to up‐ and downregulate cytochrome P450 monooxygenases (P450s) involved in detoxification of toxic xenobiotics including phytochemicals and pesticides. G‐quadruplexes (G4)‐forming DNA motifs are enriched in the promoter regions of transcription factors and function as cis‐acting elements to regulate these genes. Whether and how P450s gain and keep G4 DNA motifs to regulate their expression still remain unexplored. Here, we show that CYP321A1, a xenobiotic‐metabolizing P450 from Helicoverpa zea, a polyphagous insect of economic importance, has acquired and preserved a G4 DNA motif by selectively retaining a transposon known as HzIS1‐3 that carries this G4 DNA motif in its promoter region. The HzIS1‐3 G4 DNA motif acts as a silencer to suppress the constitutive and induced expression of CYP321A1 by plant allelochemicals flavone and xanthotoxin through folding into an intramolecular parallel or hybrid‐1 conformation in the absence or presence of K+. The G4 ligand N‐methylmesoporphyrin IX (NMM) strengthens the silencing effect of HzIS1‐3 G4 DNA motif by switching its structure from hybrid‐1 to hybrid‐2. The enrichment of transposons in P450s and other environment‐adaptation genes implies that selective retention of G4 DNA motif‐carrying transposons may be the main evolutionary route for these genes to obtain G4 DNA motifs.
Glucose as a carbon source to synthesize palmitate de novo in the adult rodent brain: Adding to the carbon recycling story in the brain

While brain glucose metabolism is known to contribute the carbons to support brain saturated and monounsaturated fatty biosynthesis de novo in the developing brains of young rodents, such a contribution to fatty acid biosynthesis in the adult brain is poorly understood. Recent work from the Bazinet laboratory illuminates the role of brain glucose metabolism in providing a carbon source from which palmitic acid is synthesized. In “The Majority of Brain Palmitic Acid is Maintained by Lipogenesis from Dietary Sugars and is Augmented in Offspring fed low Palmitic Acid Levels from Birth”, the Bazinet lab demonstrates the importance of glucose as a key contributing source of carbon for brain palmitic synthesis and that a low palmitate diet exacerbates its utilization for brain palmitate synthesis de novo. Further, this impact is found in male mice rather than female mice, which adds an additional layer of importance. Mammals are known to conserve carbon and the brain has the ability to convert a variety of carbon sources to needed molecules, depending on the physiological needs of the brain. Overall, this paper contributes an important missing piece of the puzzle regarding carbon recycling in the brain and is a key piece of evidence that indeed the adult mammalian brain can convert glucose to carbons for use in saturated fatty acid synthesis.
Anti‐drug antibodies to brolucizumab and ranibizumab in serum and vitreous of patients with ocular disease

Postapproval reports of intraocular inflammation (IOI) and occlusive retinal vasculitis following intravitreal brolucizumab are accumulating. A role of anti‐drug antibodies (ADAs) to brolucizumab is under current scientific discussion. The purpose of the present study was to measure brolucizumab ADAs in a cross‐sectional ophthalmic patient population and to compare the occurrence of brolucizumab ADAs with that of ranibizumab ADAs.
The Parallel Transformations of Polycyclic Aromatic Hydrocarbons in the Body and in the Atmosphere

Background. Polycyclic aromatic hydrocarbons (PAHs) emitted from combustion sources are known to be mutagenic, with more potent species also being carcinogenic. Previous studies show that PAHs can undergo complex transformations both in the body and in the atmosphere, yet these transformation processes are generally investigated separately. Objectives. Drawing from the literature in atmospheric chemistry and toxicology, we highlight the parallel transformations of PAHs that occur in the atmosphere and the body and discuss implications for public health. We also examine key uncertainties related to the toxicity of atmospheric oxidation products of PAHs and explore critical areas for future research. Discussion. We focus on a key mode of toxicity for PAHs, in which metabolic processes (driven by cytochrome P450 enzymes), leads to the formation of oxidized PAHs that can damage DNA. Such species can also be formed abiotically in the atmosphere from natural oxidation processes, potentially augmenting PAH toxicity by skipping the necessary metabolic steps that activate their mutagenicity. Despite the large body of literature related to these two general pathways, the extent to which atmospheric oxidation affects a PAH’s overall toxicity remains highly uncertain. Combining knowledge and promoting collaboration across both fields can help identify key oxidation pathways and the resulting products that impact public health. Conclusions. Cross-disciplinary research, in which toxicology studies evaluate atmospheric oxidation products and their mixtures, and atmospheric measurements examine the formation of compounds that are known to be most toxic. Close collaboration between research communities can help narrow down which PAHs, and which PAH degradation products, should be targeted when assessing public health risks. https://doi.org/10.1289/EHP9984
Increasing hospital admission rates for anorexia nervosa amongst young women in Australia from 1998 to 2018

Objective This study aims to describe the trends in community incidence, community prevalence, mortality, overnight hospital admission rates and average overnight inpatient length of stay (ALOS) for anorexia nervosa (AN) amongst young females aged 15-29 in Australia, between 1998–2018. Methods Hospitalisation and ALOS data was obtained from the Australian Institute of Health and Welfare principal data cubes. Epidemiological data relating to community-level incidence, community-level prevalence, disability adjusted life years (DALY) and mortality were obtained from the Global Health Data Exchange. We analysed the community and hospital rates for AN in 3 female age groups, 15-19, 20-24 and 25-29. Results Overnight hospital female admission rates for AN have substantially increased over the past two decades, with a higher rate increase between 2008-2018 for 15-29 age groups. The largest absolute increases were seen in the 15-19 female age group. Community prevalence and DALYs increased slightly, whilst community incidence has remained relatively stable. During the study period, mortality rates and the average hospital inpatient length of stay for AN declined for females 15-29 years. Conclusion Overnight hospitalisation rates for AN particularly increased amongst young females (15-29) in Australia over the past decade. Less substantial increases in community incidence, community prevalence and DALYs, and declining mortality were also observed.
Cannabidiol Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in the Inflammatory Microenvironment via the CB2-dependent p38 MAPK Signaling Pathway

Background and Objectives Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment. Methods and Results BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and presented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs’ vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively. Conclusions CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.
Mindfulness-Oriented Recovery Enhancement vs Supportive Group Therapy for Co-occurring Opioid Misuse and Chronic Pain in Primary Care

Key Points Question Does a mindfulness-based intervention reduce comorbid chronic pain and opioid misuse in the primary care setting more than supportive psychotherapy? Findings In this randomized clinical trial that included 250 adults with both chronic pain and opioid misuse, 45.0% of participants receiving Mindfulness-Oriented Recovery Enhancement (MORE) were no longer misusing opioids after 9 months of follow-up compared with 24.4% of participants receiving supportive group psychotherapy. Participants receiving MORE also reported significant improvements in chronic pain symptoms compared with those receiving supportive psychotherapy. Meaning In this study, MORE appeared to be an efficacious treatment for opioid misuse among adults with chronic pain.
Effects of Exercise Training on the Renin–Angiotensin System in the Kidneys of Dahl Salt-Sensitive Rats

ABSTRACT Purpose Exercise training (Ex) has antihypertensive and renal protective effects; however, the precise mechanisms remain unclear. The renal renin–angiotensin system (RAS) plays a vital role in renal function and pathology. Therefore, we investigated the effects of Ex on the renal RAS components in Dahl salt-sensitive (Dahl-S) rats. Methods Male Dahl-S rats were divided into four groups: normal salt diet + sedentary, normal salt diet + Ex, high-salt diet (HS, 8% NaCl) + sedentary, and HS + Ex. Treadmill running was performed for 8 wk in the Ex groups. Results Ex attenuated the HS-induced renal dysfunction and glomerular injury without causing blood pressure alterations. HS increased urinary excretion of both total and intact angiotensinogen. Ex decreased the HS-induced increased urinary excretion of total angiotensinogen. However, it did not change the HS-induced urinary excretion of intact angiotensinogen, indicating reduced intact angiotensinogen cleaving. Ex restored the HS-induced increased angiotensinogen and angiotensin II type 1 receptor expressions in the outer medulla and the HS-induced increased angiotensin-converting enzyme expression in the cortex. Ex restored the HS-induced decreased renin expression in the cortex and outer medulla, and the HS-induced decreased angiotensin-converting enzyme 2, angiotensin II type 2 receptor, and Mas receptor expressions in the outer medulla. Conclusions Ex attenuates HS-induced renal dysfunction, glomerular injury, and renal RAS dysregulation in Dahl-S rats.