Miracle-dz/UniFAR-FTUs huggingface dataset:
An optimized approach for processing of frozen lung and lavage samples for microbiome studies

The respiratory tract has a resident microbiome with low biomass and limited diversity. This results in difficulties with sample preparation for sequencing due to uneven bacteria-to-host DNA ratio, especially for small tissue samples such as mouse lungs. We compared effectiveness of current procedures used for DNA extraction in microbiome studies. Bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected to test different forms of sample pre-treatment and extraction methods to increase bacterial DNA yield and optimize library preparation. DNA extraction using a pre-treatment method of mechanical lysis (lung tissue) and one-step centrifugation (BALF) increased DNA yield and bacterial content of samples. In contrast, a significant increase of environmental contamination was detected after phenol chloroform isoamyl alcohol (PCI) extraction and nested PCR. While PCI has been a standard procedure used in microbiome studies, our data suggests that it is not efficient for DNA extraction of frozen low biomass samples. Finally, a DNA Enrichment kit was tested and found to improve the 16S copy number of lung tissue with a minor shift in microbial composition. Overall, we present a standardized method to provide high yielding DNA and improve sequencing coverage of low microbial biomass frozen samples with minimal contamination.
Sildenafil citrate as an adjuvant to clomiphene citrate for ovulation induction in polycystic ovary syndrome: crossover randomized controlled trial

Introduction To evaluate sildenafil citrate as an adjuvant to clomiphene citrate (CC) for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS). Material and methods A total of 595 infertile PCOS women were randomly assigned into either clomiphene/sildenafil (C/S) group or CC group. Transvaginal (TVS)-Doppler studies were done for participants when the dominant follicle reach 16 mm, to measure the resistance index, pulsatility index, and maximum velocity of sub-endometrial, uterine, and ovarian vessels. Participants were examined using TVS on the 21st day of the cycle to detect ovulation or, after a positive pregnancy test, for documentation of pregnancy. Participants with negative pregnancy tests were given 2 months’ rest without OI, followed by crossover of OI medication between the 2 studied groups. The crossover results were assessed by TVS, TVS-Doppler, and pregnancy test. Results The endometrial thickness was significantly higher among the C/S than the CC group during the first 3 months (9.6 ±1.2 vs. 8.7 ±1.0 mm, respectively, p = 0.003) and after crossover of OI (9.1 ±1.3 vs. 8.2 ±1.0 mm, respectively, p = 0.007). The chemical and clinical pregnancy rates were significantly higher among the C/S compared to the CC group (39.8% and 36.6% vs. 25% and 18.98%, respectively) (p = 0.01 and 0.001, respectively) during the first 3 months and after crossover of OI (36.6% and 33.1% vs. 23.8% and 20.6%, respectively) (p = 0.02 and 0.01, respectively). Conclusions SC as an adjuvant to CC for OI in PCOS women increases the chemical and clinical pregnancy rates. It also improves the endometrial thickness and ovulation rate through improved endometrial and ovarian Doppler indices.
Determination of human papillomavirus type in archival tissue specimens of invasive cervical cancer using molecular mapping and E6/E7-based polymerase chain reaction

In our previous study, an L1-based human papillomavirus (HPV) test using liquid-based cytology revealed that some invasive cervical cancers (ICC) exhibited multiple HPV types or harbored no HPV DNA. Here, molecular mapping of formalin-fixed paraffin-embedded cancer tissue specimens from the same patients were conducted to confirm these observations. Among 377 ICC cases, 73 eligible specimens (9 positive for multiple HPV types, 16 negative for HPV, and 48 positive for a single HPV type from the previous study) were reexamined by manual microdissection of cancer lesions, then subjected to HPV genotyping using the uniplex E6/E7 polymerase-chain-reaction method to detect all high-risk and potentially high-risk HPV types. The HPV typing results were confirmed in 52 of 73 cancer cases; among the 21 remaining cases, 15 were discordant and 6 were partially concordant. In total, 8 of 16 (50%) HPV-negative samples became positive; 6 were positive for HPV16 and 2 were positive for HPV67. Moreover, two samples previously positive for HPV6 and HPV53 were negative for HPV. All nine cancers with multiple HPV types were found to harbor only a single HPV type. In total, 63 cancer tissues exhibited a single HPV type. HPV16 and HPV18 were detected in squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Alpha-5 (HPV82), -6 (HPV56), and -9 (HPV31/52/67) HPV types were detected in SCC, whereas Alpha-7 (HPV59/68) types were detected in ADC and adenosquamous carcinoma (ADSCC). These findings suggested that the different HPV types induced different histological cancers. Furthermore, all SCCs and 10 of 11 usual-type ADCs were positive for high-risk HPV types, supporting the use of HPV screening for the detection of these cancers and associated premalignant lesions. HPV16 is likely to remain undetected in some cervical cancer tissues because of low viral-copy-numbers. Putative high-risk HPV types (e.g., HPV67 and HPV82) might be high risk in Japan.
Aesthetic judgment of architecture for Chinese observers

Architects should consider the aesthetic experience of potential users when designing architectures. Previous studies have shown that subjective aesthetic judgment of architectures is influenced by structure features, and Western observers prefer structures that have curvilinear contours, high ceilings, and open space. The building styles, however, vary across cultures, and it remains unclear whether the preference for contours, ceiling height, and openness exist across cultures. To investigate this issue, this study analyzes the aesthetic judgment of Chinese observers, and the results demonstrate that Chinese observers also prefer high ceilings and open space. Preference for curvilinear contours, however, interacts with ceiling height and openness. Simple effect analysis reveals that Chinese observers prefer curvilinear contours only when the ceiling is low and the space is closed. In sum, these results suggest that preference for high ceilings and open space is robust for Chinese observers, but the preference for curvilinear contours is less reliable.
Cytokine release syndrome and successful response to pembrolizumab therapy in a patient with EGFR ‐mutated non‐small‐cell lung cancer: A case report

A therapeutic option for advanced non‐small‐cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor (TKI) resistance is a clinical challenge. The clinical outcomes of pembrolizumab in those patients is inconclusive. Cytokine release syndrome (CRS) is a rarely reported immune‐related adverse event in the field of immune checkpoint inhibitors therapy, raising challenges given the paucity of data with such presentations. We present the unique case of a 67‐year‐old female with advanced EGFR‐mutated NSCLC who successfully responded to pembrolizumab after EGFR‐TKI resistance. However, the patient developed CRS after pembrolizumab initiation and presented with fever, rash, hypotension, hypoxemia, tachycardia, and multiple organ dysfunction. Blood tests showed elevated levels of peripheral CD8+ T cells, C‐reactive protein, and tumor necrosis factor‐α. The symptoms rapidly improved after corticosteroid initiation. Based on the present case, we propose that pembrolizumab might be a potential salvage therapy for patients with advanced EGFR‐mutated NSCLC after EGFR‐TKI resistance; CRS would be a sign of the antitumor effect of PD‐1 inhibitors in those patients. However, CRS can be a fatal adverse effect and clinicians must remain vigilant for the rare toxicities to make prompt diagnosis and treatment.
Topological ranks reveal functional knowledge encoded in biological networks: a comparative analysis

MOTIVATION Biological networks topology yields important insights into biological function, occurrence of diseases and drug design. In the last few years, different types of topological measures have been introduced and applied to infer the biological relevance of network components/interactions, according to their position within the network structure. Although comparisons of such measures have been previously proposed, to what extent the topology per se may lead to the extraction of novel biological knowledge has never been critically examined nor formalized in the literature. RESULTS We present a comparative analysis of nine outstanding topological measures, based on compact views obtained from the rank they induce on a given input biological network. The goal is to understand their ability in correctly positioning nodes/edges in the rank, according to the functional knowledge implicitly encoded in biological networks. To this aim, both internal and external (gold standard) validation criteria are taken into account, and six networks involving three different organisms (yeast, worm and human) are included in the comparison. The results show that a distinct handful of best-performing measures can be identified for each of the considered organisms, independently from the reference gold standard. AVAILABILITY Input files and code for the computation of the considered topological measures and K-haus distance are available at https://gitlab.com/MaryBonomo/ranking. CONTACT simona.rombo@unipa.it. SUPPLEMENTARY INFORMATION Supplementary data are available at Briefings in Bioinformatics online.
Reprogramming dysfunctional CD8+ T cells to promote properties associated with natural HIV control

Virus-specific CD8+ T cells play a central role in HIV-1 natural controllers to maintain suppressed viremia in the absence of antiretroviral therapy. These cells display a memory program that confers them stemness properties, high survival, polyfunctionality, proliferative capacity, metabolic plasticity, and antiviral potential. The development and maintenance of such qualities by memory CD8+ T cells appear crucial to achieving natural HIV-1 control. Here, we show that targeting the signaling pathways Wnt/transcription factor T cell factor 1 (Wnt/TCF-1) and mTORC through GSK3 inhibition to reprogram HIV-specific CD8+ T cells from noncontrollers promoted functional capacities associated with natural control of infection. Features of such reprogrammed cells included enrichment in TCF-1+ less-differentiated subsets, a superior response to antigen, enhanced survival, polyfunctionality, metabolic plasticity, less mTORC1 dependency, an improved response to γ-chain cytokines, and a stronger HIV-suppressive capacity. Thus, such CD8+ T cell reprogramming, combined with other available immunomodulators, might represent a promising strategy for adoptive cell therapy in the search for an HIV-1 cure.
A panorama of the medicolegal aspects of suicide assessments: integrating multiple vantage points in improving quality, safety, and risk management

Abstract Epidemiological trends in global suicides have been of serious concern in the last decade. The burden of higher expectations in the assessment of suicidal behaviors on mental health professionals is mounting. However, the suicidal risk assessment has many evolving and moving parts, and is one of the most heavily researched fields in psychiatry. Although it is clear from current empirical research that suicide cannot accurately be predicted, the standard of care from regulatory bodies and professional organizations dictates the use of established measures and following consensus guidelines. However, the legal system has different parameters to assess for the deviation from these standards and views it from a different vantage point. Therefore, it is imperative to know these critical multifaceted panoramas of suicide assessment. Considering the gaps within suicide risk assessment tools, we propose that appropriate documentation and thorough treatment planning are key to navigating the complex medicolegal risks. These approaches are useful for risk management and improve clinical outcomes, quality of care, and overall patient safety.
Dietary risk assessment of selected organophosphorus and pyrethoid pesticide residues in fresh harvested tomatoes at Makambako Town, Njombe region, Tanzania

ABSTRACT This study aimed to assess the levels of selected pesticides residues in harvested tomatoes and their associated dietary risks to consumers at Makambako Town in Njombe region, Tanzania. Forty-two fresh tomatoes were sampled among tomato farmers during harvesting season and extraction of analytes was done using QuEChERS method and analysed by Gas Chromatography-Mass Spectrometer. Residues of chlorpyrifos, profenofos, gamma cyhalothrin and cypermethrin were alternatingly detected in 78.51% of samples. The average concentrations of residues were 0.014, 0.056, 0.003 and 0.2 mg/kg for chlorpyrifos, profenofos, gamma cyhalothrin and cypermethrin and were all below their respective Codex MRLs. The highest concentration was 0.718 mg/kg for cypermethrin, above the Codex MRL of 0.2 mg/kg. The hazard indexes indicate no potential health hazards to the general population due to the lifetime consumption of fresh tomatoes from the study area. Periodic monitoring of residue levels of pesticides in vegetable fruits, including tomatoes, is recommended.
Marginal leakage in permanent teeth after dentin treatment with air abrasion and adhesive systems

Due to doubts related to the application and association of techniques for appropriate adhesion, as the air abrasion system and last generation adhesive systems, the objective of this study was to evaluate the marginal leakage in Class V composite restorations in permanent teeth prepared with rotating instruments and then submitted to air abrasion and adhesive systems. Cavities were prepared with burs in high speed in facial and lingual surfaces of 25 human third molars. The specimens were divided into 5 groups of 10 preparations each: G1 (air abrasion and Scotchbond Multi Purpose), G2 (phosphoric acid and Scotchbond MP), G3 (Clearfil SE Bond self-etching system), G4 (air abrasion, phosphoric acid and Scotchbond MP) G5 (air abrasion and Clearfil SE Bond). All groups were restored with Z100 composite resin. The teeth were subjected to thermal cycling and immerged in 50% silver nitrate solution. After sectioning, the specimens were analyzed with a stereomicroscope for assessment of microleakage according to the degree of dye penetration. The Kruskal-Wallis test followed by Dunn Multiple Comparison test were performed in order to evaluate the differences among the experimental groups. Air abrasion groups demonstrated the greatest leakage. Scotchbond MP with phosphoric acid produced the least leakage, with greater leakage in gingival margins than occlusal margins in all experimental groups. It was concluded that dentin treatment with air abrasion should not be used in permanent teeth to reduce the marginal leakage.
Measuring Patient Compliance With Remote Monitoring Following Discharge From Hospital After Major Surgery (DREAMPath): Protocol for a Prospective Observational Study

Background The incidence of major surgery is on the rise globally, and more than 20% of patients are readmitted to hospital following discharge from hospital. During their hospital stay, patients are monitored for early detection of clinical deterioration, which includes regularly measuring physiological parameters such as blood pressure, heart rate, respiratory rate, temperature, and pulse oximetry. This monitoring ceases upon hospital discharge, as patients are deemed clinically stable. Monitoring after discharge is relevant to detect adverse events occurring in the home setting and can be made possible through the development of digital technologies and mobile networks. Smartwatches and other technological devices allow patients to self-measure physiological parameters in the home setting, and Bluetooth connectivity can facilitate the automatic collection and transfer of this data to a secure server with minimal input from the patient. Objective This paper presents the protocol for the DREAMPath (Domiciliary Recovery After Medicalization Pathway) study, which aims to measure compliance with a multidevice remote monitoring kit after discharge from hospital following major surgery. Methods DREAMPath is a single-center, prospective, observational, cohort study, comprising 30 patients undergoing major intracavity surgery. The primary outcome is to assess patient compliance with wearable and interactive smart technology in the first 30 days following discharge from hospital after major surgery. Secondary outcomes will explore the relation between unplanned health care events and physiological data collected in the study, as well as to explore a similar relationship with daily patient-reported outcome measures (Quality of Recovery–15 score). Secondary outcomes will be analyzed using appropriate regression methods. Cardiopulmonary exercise testing data will also be collected to assess correlations with wearable device data. Results Recruitment was halted due to COVID-19 restrictions and will progress once research staff are back from redeployment. We expect that the study will be completed in the first quarter of 2022. Conclusions Digital health solutions have been recently made possible due to technological advances, but urgency in rollout has been expedited due to COVID-19. The DREAMPath study will inform readers about the feasibility of remote monitoring for a patient group that is at an increased risk of acute deterioration. Trial Registration ISRCTN Registry ISRCTN62293620; https://www.isrctn. com/ISRCTN62293620 International Registered Report Identifier (IRRID) DERR1-10.2196/30638
How measurements affected by medication use are reported and handled in observational research: A literature review

In epidemiological research, measurements affected by medication, for example, blood pressure lowered by antihypertensives, are common. Different ways of handling medication are required depending on the research questions and whether the affected measurement is the exposure, the outcome, or a confounder. This study aimed to review handling of medication use in observational research.
CAD Techniques for Robust FPGA Design Under Variability

The imperfections in the semiconductor fabrication process and uncertainty in operating environment of VLSI circuits have emerged as critical challenges for the semiconductor industry. These are generally termed as process and environment variations, which lead to uncertainty in performance and unreliable operation of the circuits. These problems have been further aggravated in scaled nanometer technologies due to increased process variations and reduced operating voltage. Several techniques have been proposed recently for designing digital VLSI circuits under variability. However, most of them have targeted ASICs and custom designs. The flexibility of reconfiguration and unknown end application in FPGAs make design under variability different for FPGAs compared to ASICs and custom designs, and the techniques proposed for ASICs and custom designs cannot be directly applied to FPGAs. Very few techniques have been proposed for FPGA design under variability, with varying degrees of improvement in timing/power variability. However, these have not dealt with leveraging CAD, architecture and circuits co-design methodologies for FPGA design under variability, and further, have not accounted for the impact of the variability in Vdd arising due to IR drops which is important because the performance of a circuit becomes more sensitive to process parameters as Vdd is reduced. An important design consideration is to minimize the modifications in architecture and circuit to reduce the cost of changing the existing FPGA architecture and circuit. The work in this thesis develops CAD and architecture/circuit design techniques for FPGAs to improve the timing and power yield of FPGA designs under process variations. In the case of environment variations this work focuses on developing design techniques for reducing IR-drops. The focus of this work can be divided into three principal categories, which are, improving timing yield under process variations, improving power yield under process variations and improving the voltage profile in the FPGA power grid. The work on timing yield improvement implements a Statistical Static Timing Analysis (SSTA) framework to analyze the circuit delay under process variations, such that the statistical distribution of the critical delay can be computed. In this work, the structure of the interconnect is analyzed and it is shown that an optimum number of buffers can be inserted in the interconnect to reduce the variation in circuit delay. Several interconnect architectures are analyzed, under the constraints of the FPGA structure, to find the best architecture which leads to smallest (μ + 3σ) of the critical delay. The placement and routing tools are then enhanced such that the delay variability is accounted for when optimizing the critical delay of the circuit. Results indicate that up to 28% improvement in (μ+ 3σ) of the critical delay can be obtained from the proposed methodology. The work on power yield improvement for FPGAs selects a low power dual-Vdd FPGA design as the baseline FPGA architecture for developing power yield enhancement tech-
Women’s Motivators to Engage in Opioid Use Disorder Treatment While Enrolled in an Opioid Intervention Court

Abstract IntroductionTo address the rising presence of opioid use disorder in the United States, states have begun to implement specialized opioid intervention courts to provide immediate support for individuals at risk of opioid overdose. The present study sought to understand the motivations of women to engage in treatment while enrolled in an opioid intervention court. MethodsWe conducted 31 in-depth, qualitative interviews with women enrolled in an opioid intervention court in Buffalo, NY, to better understand their motivation regarding opioid use treatment. The data indicated a combined social-ecological and self-determination theory framework. ResultsThematic analysis revealed four themes across the Social-Ecological Model that aligned with motivation-related needs of autonomy, competence, and relatedness, as defined by Self-Determination Theory. Themes at each level of the Social-Ecological Model described either support for or undermining of women’s motivation for treatment: (1) individual level: personal motivation for change, (2) interpersonal level: support for OUD treatment-related autonomy, competence, and relatedness, (3) community level: court systems provide pathways to treatment, and (4) society level: insufficient social resources can undermine competence. ConclusionsThe findings provide new insights into various factors across all levels of the Social-Ecological Model that influence motivation for opioid use disorder treatment among women enrolled in opioid intervention court. Results support the possibility to integrate programs rooted in Self-Determination Theory to support opioid use disorder treatment among justice-involved persons.