Miracle-dz/UniFAR-FTUs huggingface dataset:
Response of individual airways in vivo to bronchial thermoplasty.

Bronchial thermoplasty (BT) is a treatment for moderate-to-severe asthma which generally improves quality-of-life scores but not conventional measures of lung function. Newer methodologies have begun to demonstrate the underlying physiological changes and elucidate the mechanism of action. We postulated that systematic, CT-based assessment of the response of individual airways to BT is feasible, and our aim was to determine the distribution of these responses and the relationship with airway size. Twenty patients meeting the ERS/ATS definition of severe asthma underwent BT and assessment including CT, Asthma Control Questionnaire (ACQ), and spirometry. Treatment was structured so that the left and right lungs are treated sequentially with a mid-treatment assessment providing an internal control. Pairs of CT scans were analysed using a new semi-automatic processing algorithm which matched individual segmented airways for quantitative comparison. Cross-sectional airway lumen area from matched airway pairs in treated lungs increased on average by 6.4% after BT (p<0.02) but showed no change in the untreated lung. Matched airway length was also unchanged. Breakdown by airway size showed amplified response in more distal airways, with the smallest quintile of measured airways dilating by 13.2% (p<0.001). ACQ improved from 3.5±0.9 to 1.9±1.2 (p<0.001). These data show that the response to BT in individual airways can be assessed by CT and that dilation is heterogeneous and predominant in distal compared with proximal airways. A CT-based approach may further our understanding of the physiological changes in BT and aid in the development of refined and personalised versions of the therapy.
Proteomic profiling of human uterine extracellular vesicles reveal dynamic regulation of key players of embryo implantation and fertility during menstrual cycle

Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biology. However, how their proteome is regulated throughout the menstrual cycle is not known. Such information can provide novel insights into biological processes critical for embryo development, implantation, and successful pregnancy. Using mass spectrometry‐based quantitative proteomics, we show that small EVs (sEVs) isolated from uterine lavage of fertile women (UL‐sEV), compared to infertile women, are laden with proteins implicated in antioxidant activity (SOD1, GSTO1, MPO, CAT). Functionally, sEVs derived from endometrial cells enhance antioxidant function in trophectoderm cells. Moreover, there was striking enrichment of invasion‐related proteins (LGALS1/3, S100A4/11) in fertile UL‐sEVs in the secretory (estrogen plus progesterone‐driven, EP) versus proliferative (estrogen‐driven, E) phase, with several players downregulated in infertile UL‐sEVs. Consistent with this, sEVs from EP‐ versus E‐primed endometrial epithelial cells promote invasion of trophectoderm cells. Interestingly, UL‐sEVs from fertile versus infertile women carry known players/predictors of embryo implantation (PRDX2, IDHC), endometrial receptivity (S100A4, FGB, SERPING1, CLU, ANXA2), and implantation success (CAT, YWHAE, PPIA), highlighting their potential to inform regarding endometrial status/pregnancy outcomes. Thus, this study provides novel insights into proteome reprograming of sEVs and soluble secretome in uterine fluid, with potential to enhance embryo implantation and hence fertility.
Immediate implant placement in fresh extraction sockets

Immediate implant placement (IIP) in fresh extraction sockets exhibits similar survival and success rates to delayed implant placement in healed sockets. Several advantages of IIP involve shortened total treatment time, reduction of the number of invasive surgeries, and subsequent reduction of patient discomfort due to lack of additional surgeries. The major shortcomings in IIP, however, include the inability to obtain early bony support, presence of a gap between the extraction socket and fixture, and the inability to cover the fixture with soft tissue, leading to increased risk of infection and implant loss. When IIP is performed, atraumatic or minimally traumatic extractions, conservation of the septal bone in molars, minimal flap elevation or flapless surgery, bone grafting the gap between the fixture and the extraction socket, and coverage with soft tissue or a membrane must be considered.
Aesthetic Scar-Less Mastectomy and Breast Reconstruction

Surgical approaches in breast cancer have been changing to ensure both oncologic safety and cosmetic results. Although the concept of “oncoplastic breast surgery” has been accepted for decades, breast and plastic surgeons have been striving to develop more advanced surgical skills that ensure non-inferior oncologic outcomes with better cosmetic outcomes. Endoscopic or robotic devices, which are currently available only for chest or abdominal surgeries, could be used for breast surgery to ensure better cosmetic outcomes. The authors refer to this surgical concept as “aesthetic scar-less breast surgery and reconstruction,” a term that encompasses the consequential concepts rather than naming it with simple technical words such as endoscopy-assisted or robot-assisted surgery. The “scar-less” term simply means leaving less of a scar, and better results can be expected by designing incisions on invisible areas. Herein, we summarize our experiences with various techniques of “aesthetic scar-less” surgery and review the existing literature on this topic.
Sudden sensorineural hearing loss during pregnancy: etiology, treatment, and outcome

Objective To analyze the etiologies, treatments, and outcomes of sensorineural hearing loss (SSNHL) during pregnancy. Study design Retrospective chart review of 25 pregnant patients treated for SSNHL between January 2012 and September 2019. Forty-nine age matched non-pregnant women with severe and profound hearing loss diagnosed with SSNHL during the same period served as controls. Data were recorded on age, symptoms, onset of hearing loss, audiometric results, treatments, and outcomes. Results The mean age was 29.6 years (range 23–38 years). Intratympanic steroids (ITS) were administered in 15 (60.0%) pregnant women with SSNHL. Three women were treated with postauricular steroids only, while another woman was treated with intravenous ginkgo leaf extract and dipyridamole. The remaining six women received no medications. More than half (8/15, 53.3%) of pregnant women with SSNHL receiving ITS experienced hearing improvement. Pregnant women with profound hearing loss who received no medication had no hearing improvement. Most pregnant women with SSNHL (12/15, 80.0%) had higher fibrinogen levels than controls (mean values 3.77±0.71 g/L and 2.54±0.48 g/L, respectively). Conclusion Fibrinogen could be a risk factor for SSNHL during pregnancy. ITS may benefit pregnant women with severe and profound SSNHL.
Thai Nurses' Experiences of Spiritual Care for Older Adults at End of Life

Most Thai registered nurses who provide end-of-life care emphasize the physical dimension of care rather than spiritual care. There is a need to explore the experiences of Thai nurses who provide spiritual care. The purpose of the study was to explore the experiences of Thai palliative care nurses providing spiritual care for older adults at the end of life. A descriptive qualitative research design was used. The 8 participants were Thai nurses with experience of palliative care in hospitals in the central, northeastern, northern, and southern regions of Thailand. A focus group discussion was used for data collection. Content analysis was used to analyze data. Five themes were as follows: (1) spiritual care was searching for meaning in patients' lives, (2) spiritual self-preparation of nurses for making sense and connecting to patients' spirituality, (3) caring for patients' spiritual needs by recognizing psychological and religious beliefs, (4) facilitating ways to ease patients' suffering, and (5) assuring confidence of patients and relatives for receiving the best care. These findings that should be included in training registered nurses are honoring the patients' lives, addressing spiritual needs to decrease patients' suffering, and enhancing patients' perceptions of care through spiritual self-preparation and spiritual concern of nurses.
Financial reward has differential effects on behavioural and self-report measures of listening effort

Abstract Objectives To investigate the effects of listening demands and motivation on listening effort (LE) in a novel speech recognition task. Design We manipulated listening demands and motivation using vocoded speech and financial reward, respectively, and measured task performance (correct response rate) and indices of LE (response times (RTs), subjective ratings of LE and likelihood of giving up). Effects of inter-individual differences in cognitive skills and personality on task performance and LE were also assessed within the context of the Cognitive Energetics Theory (CET). Study sample Twenty-four participants with normal-hearing (age range: 19 − 33 years, 6 male). Results High listening demands decreased the correct response rate and increased RTs, self-rated LE and self-rated likelihood of giving up. High financial reward increased subjective LE ratings only. Mixed-effects modelling showed small fixed effects for competitiveness on LE measured using RTs. Small fixed effects were found for cognitive skills (lexical decision RTs and backwards digit span) on LE measured using RTs and correct response rate, respectively. Conclusions The effects of listening demands on LE in the speech recognition task aligned with CET, whereas predictions regarding the influence of motivation, cognitive skills and personality were only partially supported.
Differential susceptibility 2.0: Are the same children affected by different experiences and exposures?

Abstract Differential susceptibility theory stipulates that some children are more susceptible than others to both supportive and adverse developmental experiences/exposures. What remains unclear is whether the same individuals are most affected by different exposures (i.e., domain general vs. specific). We address this issue empirically for the first time using, for illustrative and proof-of-principle purposes, a novel influence-statistics’ method with data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care. Results indicated that previously documented effects of greater quality of care on enhanced pre-academic skills and greater quantity of care on more behavior problems apply mostly to different children. Analyses validating the new method indicated, as predicted, that (a) the quantity-of-care effect applied principally to children from more socioeconomically advantaged families and that (b) being highly susceptible to both, one or neither childcare effect varied as a function of a three-gene, polygenic-plasticity score (serotonin transporter linked polymorphic region [5-HTTLPR], dopamine receptor D4 [DRD4], brain-derived neurotrophic factor [BDNF]) in a dose–response manner (i.e., 2>1>0). While domain-specific findings involving child-care effects cannot be generalized to other environmental influences, the influence-statistics’ approach appears well suited for investigating the generality–specificity of environment effects, that is, of “differential, differential susceptibility. ”
The Monoacylglycerol Lipase Inhibitor JZL184 Inhibits Lung Cancer Cell Invasion and Metastasis via the CB1 Cannabinoid Receptor

A targeted modulation of the endocannabinoid system is currently discussed as a promising strategy for cancer treatment. An important enzyme for the endocannabinoid metabolism is the monoacylglycerol lipase (MAGL), which catalyzes the degradation of 2-arachidonoylglycerol (2-AG) to glycerol and free fatty acids. In this study, we investigated the influence of MAGL inhibition on lung cancer cell invasion and metastasis. Using LC-MS, significantly increased 2-AG levels were detected in A549 cells treated with the MAGL inhibitor JZL184. In athymic nude mice, JZL184 suppressed metastasis of A549 cells in a dose-dependent manner, whereby the antimetastatic effect was cancelled by the CB1 receptor antagonist AM-251. In vitro, JZL184 induced a time- and concentration-dependent reduction of A549 cell invasion through Matrigel-coated membranes, which was likewise reversed by AM-251. An MAGL inhibition–associated reduction of free fatty acids as a cause of the anti-invasive effect could be excluded by add-back experiments with palmitic acid. Both JZL184 and the MAGL substrate 2-AG led to an increased formation of the tissue inhibitor of metalloproteinase-1 (TIMP-1), whereby a TIMP-1 knockdown using siRNA significantly attenuated the anti-invasive effects of both substances. Decreased invasion and TIMP-1 upregulation was also caused by the MAGL inhibitors JW651 and MJN110 or transfection with MAGL siRNA. A CB1- and TIMP-1–dependent anti-invasive effect was further confirmed for JZL184 in H358 lung cancer cells. In conclusion, MAGL inhibition led to a CB1-dependent decrease in human lung cancer cell invasion and metastasis via inhibition of 2-AG degradation, with TIMP-1 identified as a mediator of the anti-invasive effect.
Umbilical Cord Management for Newborns <34 Weeks' Gestation: A Meta-analysis

In this systematic review and meta-analysis, we synthesize the effects of umbilical cord management strategies (timing of clamping, cord milking) in preterm infants <34 weeks’ gestational age. BrightcoveDefaultPlayer10.1542/6176788642001PEDS-VA_2020-0576 Video Abstract CONTEXT: The International Liaison Committee on Resuscitation prioritized scientific review of umbilical cord management strategies at preterm birth. OBJECTIVE: To determine the effects of umbilical cord management strategies (including timing of cord clamping and cord milking) in preterm infants <34 weeks’ gestation. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, CINAHL, and trial registries were searched through July 2019 for randomized controlled trials assessing timing of cord clamping and/or cord milking. STUDY SELECTION: Two authors independently assessed trial eligibility, extracted data, appraised risk of bias, and assessed evidence certainty (GRADE). DATA EXTRACTION: We identified 42 randomized controlled trials (including 5772 infants) investigating 4 different comparisons of cord management interventions. RESULTS: Compared to early cord clamping, delayed cord clamping (DCC) and intact-cord milking (ICM) may slightly improve survival; however, both are compatible with no effect (DCC: risk ratio: 1.02, 95% confidence interval: 1.00 to 1.04, n = 2988 infants, moderate certainty evidence; ICM: risk ratio: 1.02, 95% confidence interval: 0.98 to 1.06, n = 945 infants, moderate certainty evidence). DCC and ICM both probably improve hematologic measures but may not affect major neonatal morbidities. LIMITATIONS: For many of the included comparisons and outcomes, certainty of evidence was low. Our subgroup analyses were limited by few researchers reporting subgroup data. CONCLUSIONS: DCC appears to be associated with some benefit for infants born <34 weeks. Cord milking needs further evidence to determine potential benefits or harms. The ideal cord management strategy for preterm infants is still unknown, but early clamping may be harmful.
The Phosphoprotein Synapsin Ia Regulates the Kinetics of Dense-Core Vesicle Release

Common fusion machinery mediates the Ca2+-dependent exocytosis of synaptic vesicles (SVs) and dense-core vesicles (DCVs). Previously, Synapsin Ia (Syn Ia) was found to localize to SVs, essential for mobilizing SVs to the plasma membrane through phosphorylation. However, whether (or how) the phosphoprotein Syn Ia plays a role in regulating DCV exocytosis remains unknown. To answer these questions, we measured the dynamics of DCV exocytosis by using single-vesicle amperometry in PC12 cells (derived from the pheochromocytoma of rats of unknown sex) overexpressing wild-type or phosphodeficient Syn Ia. We found that overexpression of phosphodeficient Syn Ia decreased the DCV secretion rate, specifically via residues previously shown to undergo calmodulin-dependent kinase (CaMK)-mediated phosphorylation (S9, S566, and S603). Moreover, the fusion pore kinetics during DCV exocytosis were found to be differentially regulated by Syn Ia and two phosphodeficient Syn Ia mutants (Syn Ia-S62A and Syn Ia-S9,566,603A). Kinetic analysis suggested that Syn Ia may regulate the closure and dilation of DCV fusion pores via these sites, implying the potential interactions of Syn Ia with certain DCV proteins involved in the regulation of fusion pore dynamics. Furthermore, we predicted the interaction of Syn Ia with several DCV proteins, including Synaptophysin (Syp) and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins. By immunoprecipitation, we found that Syn Ia interacted with Syp via phosphorylation. Moreover, a proximity ligation assay (PLA) confirmed their phosphorylation-dependent, in situ interaction on DCVs. Together, these findings reveal a phosphorylation-mediated regulation of DCV exocytosis by Syn Ia. SIGNIFICANCE STATEMENT Although they exhibit distinct exocytosis dynamics upon stimulation, synaptic vesicles (SVs) and dense-core vesicles (DCVs) may undergo co-release in neurons and neuroendocrine cells through an undefined molecular mechanism. Synapsin Ia (Syn Ia) is known to recruit SVs to the plasma membrane via phosphorylation. Here, we examined whether Syn Ia also affects the dynamics of DCV exocytosis. We showed that Syn Ia regulates the DCV secretion rate and fusion pore kinetics during DCV exocytosis. Moreover, Syn Ia-mediated regulation of DCV exocytosis depends on phosphorylation. We further found that Syn Ia interacts with Synaptophysin (Syp) on DCVs in a phosphorylation-dependent manner. Thus, these results suggest that Syn Ia may regulate the release of DCVs via phosphorylation.
The unveiled reality of human papillomavirus as risk factor for oral cavity squamous cell carcinoma

The prognostic impact of human papillomavirus (HPV) in oropharyngeal cancer is generally acknowledged, and HPV‐status is assessed routinely in clinical practice. Paradoxically, while the oral cavity seems the predilection site for productive HPV‐infections, figures on HPV‐attribution in oral cavity squamous cell carcinoma (OCSCC) differ widely, and prognostic impact is uncertain. Major obstacles are the lack of reproducible assays to detect HPV in nonoropharyngeal cancers, the relatively small cohorts studied and consequently the shortfall of convincing data. In our study, we used a validated, nucleic acid‐based workflow to assess HPV‐prevalence in a consecutive cohort of 1016 OCSCCs, and investigated its prognostic impact. In parallel, we analyzed p16‐immunohistochemistry (p16‐IHC) as surrogate marker for transforming HPV‐infection and independent prognosticator. All OCSCC‐patients diagnosed between 2008 and 2014 at two Dutch university medical centers were included (N = 1069). Formalin‐fixed, paraffin‐embedded (FFPE)‐samples of 1016 OCSCCs could be retrieved. Punch biopsies were taken from the tumor area in the FFPE‐blocks and tested for HPV. P16‐IHC was performed on 580 OCSCCs, including all HPV‐positive tumors. From 940 samples (92.5%), nucleic acids were of sufficient quality for HPV‐testing. In total, 21 (2.2%) OCSCCs were HPV DNA‐positive. All HPV DNA‐positive tumors were E6 mRNA‐positive and considered as true HPV‐positive. There was no difference in survival between HPV‐positive and HPV‐negative OCSCCs. In total, 46 of 580 (7.9%) OCSCCs were p16‐immunopositive, including all HPV‐positive tumors. Survival was comparable in p16‐positive and p16‐negative OCSCCs. To conclude, HPV‐prevalence is very low in OCSCC and neither HPV‐status nor p16‐status affects outcome. Based on these data, determining HPV‐status in OCSCC seems irrelevant for clinical management.
Awareness of and willingness to use pre-exposure prophylaxis (PrEP) among people who inject drugs and men who have sex with men in India: Results from a multi-city cross-sectional survey

Introduction Pre-exposure prophylaxis (PrEP) is effective in reducing HIV transmission among key populations. In India, where PrEP is not currently part of the national HIV program, little is known about PrEP awareness, willingness to use PrEP, and barriers to uptake among people who inject drugs (PWID) and men who have sex with men (MSM). Methods We used respondent-driven sampling to accrue PWID and MSM in 22 sites from August 2016 to May 2017. Participants were asked about awareness of PrEP, willingness to use PrEP (following a brief description) and reasons why they might not be willing to use PrEP. Participants were also queried on preferences for PrEP delivery modality (oral vs. injectable). Multi-level logistic regression models were used to determine participant correlates of willingness to use PrEP. Estimates were weighted for the sampling method. Results A total of 10,538 PWID and 8,621 MSM who self-reported being HIV-negative were included in the analysis. Only 6.1% (95% confidence interval [CI]: 5.9, 6.3) of PWID and 8.0% of MSM (95% CI: 7.7, 8.4) were aware of PrEP. However, willingness to use PrEP was substantially higher in both groups: 52.4% of PWID and 67.6% of MSM. Participants commonly cited a perceived low risk for acquiring HIV infection, being perceived by others as being HIV-positive, and side effects as reasons why they would be unwilling to use PrEP. Among PWID, sharing needles and hazardous alcohol use were associated with increased willingness to use PrEP. Among MSM, having a main male partner and injection drug use were associated with increased willingness to use PrEP. Preference for daily oral or monthly injectable PrEP was similar among MSM (39.6%% vs. 41.7%,), while PWID were more likely to prefer oral to injectable administration routes (56.3% vs. 31.1%). Conclusions As India plans to roll-out of PrEP in the public sector, our multi-city survey of PWID and MSM highlights the need for key population-focused education campaigns about PrEP and self-assessment of risk.
Effect of Some Trace Elements on Growth, Yield and Chemical Constituents of Trachyspermum ammi L (AJOWAN) Plants under Sinai Conditions

spraying of iron, zinc and ma nganese as each alone at 50 or 100 ppm or in triple combination of them at 50 ppm for each on plant grown under sandy soil conditions resulted in significant enhancement o f t he vegetative characters of Trachyspermum a mmi L. i n addition to essential oil percentage, es sential oil yield/plant, oil components ,N PK, F e, Z n, M n and total c arbohydrate content i n the herb. The triple combination of them surpassed the solo application of each. The major oil component was thym ol giv ing 55.51% with the triple combination. N-cymene came in the second order of thymol giving 31.42% and a-terpinene in the third order b y 2 0.66% and followed by a-pinene in the 2.62% for th e same treatment.