Miracle-dz/UniFAR-FTUs huggingface dataset:
Sostdc1 Suppression in the Absence of Sclerostin Potentiates Anabolic Action of Cortical Bone in Mice

The development of Wnt‐based osteoanabolic agents has progressed rapidly in recent years, given the potent effects of Wnt modulation on bone homeostasis. Simultaneous pharmacologic inhibition of the Wnt antagonists sclerostin and Dkk1 can be optimized to create potentiated effects in the cancellous bone compartment. We looked for other candidates that might be co‐inhibited along with sclerostin to potentiate the effects in the cortical compartment. Sostdc1 (Wise), like sclerostin and Dkk1, also binds and inhibits Lrp5/6 coreceptors to impair canonical Wnt signaling, but Sostdc1 has greater effects in the cortical bone. To test this concept, we deleted Sostdc1 and Sost from mice and measured the skeletal effects in cortical and cancellous compartments individually. Sost deletion alone produced high bone mass in all compartments, whereas Sostdc1 deletion alone had no measurable effects on either envelope. Mice with codeletion of Sostdc1 and Sost had high bone mass and increased cortical properties (bone mass, formation rates, mechanical properties), but only among males. Combined administration of sclerostin antibody and Sostdc1 antibody in wild‐type female mice produced potentiation of cortical bone gain despite no effect of Sostdc1 antibody alone. In conclusion, Sostdc1 inhibition/deletion can work in concert with sclerostin deficiency to improve cortical bone properties. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
APSified OCT-angiography analysis: Macula vessel density in healthy eyes during office hours

Purpose Optical coherence tomography angiography (OCT-A) can visualize retinal capillary microcirculation non-invasively. In order to investigate potential factors influencing OCT-A diagnostics, the aim of the present study was to determine circadian changes in macular vessel density (VD) in healthy adults during office hours, considering axial length (AL) and subfoveal choroidal thickness (CT). Methods In the prospective study 30 eyes of 30 healthy subjects (mean age 28.7 ± 11.8, range 19–60 years) were recruited who underwent repeated measurements of AL, subfoveal CT and three-layer macula VD (superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP)) on a single day at three predetermined timepoints (9 AM, 3 PM, and 9 PM). For better intra- and interindividual scan comparability, the new Anatomic Positioning System function (APS, part of Glaucoma Module Premium Edition [GMPE], Heidelberg Engineering, Germany) allowing analysis of identical retinal areas, was used for quantitative OCT-A analysis. Results Overall mean macula VD was unchanged during office hours in SVP, ICP and DCP, respectively (p>0.05). In addition, AL and CT showed no statistically significant changes over time (p>0.05). Rather, a large interindividual variance of VD with different peak time was observed. Contrary to the overall data, sectorial VD changed in dependency of office hours in all layers with an increase of VD in SVP between 9 AM and 9 PM (p = 0.003), in ICP between 3 PM and 9 PM (p = 0.000), in DCP between 9 AM and 9 PM (p = 0.048), and 3 PM and 9 PM (p = 0.000), respectively. Conclusion Overall mean macula VD, subfoveal CT and AL tended not to show statistically significant changes over time in this cohort, whereas a regional analysis of VD did. Therefore, a circadian influence on capillary microcirculation should be kept in mind. Moreover, the results highlight the importance of a more detailed analysis of VD in different sectors and different vascular layers. In addition, the pattern of diurnal variation could vary inter-individually, thus a patient-specific fluctuation pattern would need to be considered when evaluating these parameters in clinical practice.
Video based monitoring systems for hand hygiene compliance auditing: What do patients think?

Background Compliance with hand hygiene by healthcare workers is a vital aspect of the quality and safety in healthcare. The current method of monitoring compliance, known as direct observation, has been questioned as have the various electronic measures proposed as alternatives. In our earlier work we established the capacity of video-based monitoring systems (VMS) to collect data with increased efficacy, efficiency and accuracy. However, the spectre of the approach being seen as an unacceptable invasion of patient privacy, was raised as a barrier to implementation by healthcare workers. Methods In depth, semi structured interviews were conducted with 8 patients in order to explore their beliefs and options regarding the proposed approach. Interviews were transcribed and then thematic and content analysis was conducted in order to uncover themes from the data. Results Despite healthcare worker predictions, patients were generally accepting of the use of video-based monitoring systems for the auditing of hand hygiene compliance. However, this acceptance was conditional. Four interconnected themes emerged from the interview data; quality and safety of care versus privacy, consumer Involvement–knowledge, understanding and consent, technical features of the system, and rules of operation. Conclusion The use of within zone VMS approaches to hand hygiene auditing has the potential to improve the efficacy, efficiency and accuracy of hand hygiene auditing and hence the safety and quality of healthcare. By combining a suite of technical and operational specifications with high level consumer engagement and information the acceptability of the approach for patients may be significantly enhanced.
Impact of asparaginase discontinuation on outcomes of children with acute lymphoblastic leukaemia receiving the Japan Association of Childhood Leukaemia Study ALL‐02 protocol

Asparaginase is an essential drug for acute lymphoblastic leukaemia (ALL) treatment, but has several side effects, and its discontinuation often compromises patient outcomes. In the prospective Japan Association of Childhood Leukaemia Study ALL‐02 protocol, two major changes were made: (1) additional chemotherapies to compensate for the reduction of treatment intensity when asparaginase was discontinued and (2) more intensive concomitant corticosteroid administration, relative to our previous ALL‐97 protocol. In ALL‐02 study, 1192 patients were included and L‐asparaginase was discontinued for 88 (7.4%). Discontinuation due to allergy was markedly decreased relative to the ALL‐97 protocol (2.3% vs 15.4%). Event‐free survival (EFS) among patients with T‐ALL was compromised when L‐asparaginase was discontinued, as well as among patients with high‐risk B‐cell ALL, especially when discontinued before maintenance therapy. Moreover, multivariate analysis identified discontinuation of L‐asparaginase as an independent poor prognostic factor for EFS. In the current study, additional chemotherapies failed to fully compensate for L‐asparaginase discontinuation, illustrating the difficulty of replacing asparaginase with other classes of drugs, although this study was not designed to evaluate the effect of these modifications. Concomitant intensive corticosteroid treatment may help to reduce allergy to asparaginase. These results will assist in further optimization of asparaginase use.
Real-Time Multimodel Superensemble Forecasts of Atlantic Tropical Systems of 1999

Abstract In this paper, Atlantic hurricane forecasts for the year 1999 are addressed. The methodology for these forecasts is called the multimodel superensemble. This statistical method makes use of the real-time forecasts provided by a number of operational and research models to construct the superensemble forecasts. This method divides the forecast time line into two phases: a training phase and a forecast combining phase. The training phase includes an inventory of past applicable hurricane forecasts, each by the multimodels. The model biases of position and intensity errors of past forecasts are summarized via a simple linear multiple regression of these forecasts against the best-observed estimates of position and intensity. These statistics are next passed on to future forecasts of the multimodels in order to forecast the hurricanes of 1999. This method was first tested for the hurricanes of 1998 with considerable success, with some of those results summarized here. Those statistics were refined fo.
Marketing of commercial milk formula during COVID‐19 in Indonesia

Abstract Baby food marketing poses a substantial barrier to breastfeeding, which adversely affects mothers' and children's health. Over the last decade, the baby food industry has utilised various marketing tactics in Indonesia, including direct marketing to mothers and promoting products in public spaces and within the healthcare system. This study examined the marketing of commercial milk formula (CMF) and other breast‐milk substitute products during the COVID‐19 pandemic in Indonesia. Using a local, community‐based reporting platform, information on publicly reported violations of the International Code of Marketing of Breast‐milk Substitutes and subsequent World Health Assembly resolutions (the Code) was collected. It was found that a total of 889 reported cases of unethical marketing of such products were recorded primarily through social media from May 20 through December 31, 2021. Our results suggest that the COVID‐19 pandemic has provided more opportunities for the baby food industry in Indonesia to attempt to circumvent the Code aggressively through online marketing strategies. These aggressive marketing activities include online advertisements, maternal child health and nutrition webinars, Instagram sessions with experts, and heavy engagement of health professionals and social media influencers. Moreover, product donations and assistance with COVID‐19 vaccination services were commonly used to create a positive image of the baby food industry in violation of the Code. Therefore, there is an urgent need to regulate the online marketing of milk formula and all food and beverage products for children under the age of 3.
Impact of sternotomy and pericardiotomy on cardiopulmonary haemodynamics in a large animal model

What is the central question of this study? Invasive cardiovascular instrumentation can occur through closed‐ or open‐chest approaches. To what extent will sternotomy and pericardiotomy affect cardiopulmonary variables? What is the main finding and its importance? Opening of the thorax decreased mean systemic and pulmonary pressures. Left ventricular function improved, but no changes were observed in right ventricular systolic measures. No consensus or recommendation exists regarding instrumentation. Methodological differences risk compromising rigour and reproducibility in preclinical research.
Enhancing Exposure Treatment for Youths With Chronic Pain: Co-design and Qualitative Approach

Background Increasing the access to and improving the impact of pain treatments is of utmost importance, especially among youths with chronic pain. The engagement of patients as research partners (in contrast to research participants) provides valuable expertise to collaboratively improve treatment delivery. Objective This study looked at a multidisciplinary exposure treatment for youths with chronic pain through the lens of patients and caregivers with the aim to explore and validate treatment change processes, prioritize and develop ideas for improvement, and identify particularly helpful treatment elements. Methods Qualitative exit interviews were conducted with patients and caregivers at their discharge from 2 clinical trials (ClinicalTrials.gov NCT01974791 and NCT03699007). Six independent co-design meetings were held with patients and caregivers as research partners to establish a consensus within and between groups. The results were validated in a wrap-up meeting. Results Patients and caregivers described that exposure treatment helped them better process pain-related emotions, feel empowered, and improve their relationship with each other. The research partners developed and agreed upon 12 ideas for improvement. Major recommendations include that pain exposure treatment should be disseminated more not only among patients and caregivers but also among primary care providers and the general public to facilitate an early referral for treatment. Exposure treatment should allow flexibility in terms of duration, frequency, and delivery mode. The research partners prioritized 13 helpful treatment elements. Most of the research partners agreed that future exposure treatments should continue to empower patients to choose meaningful exposure activities, break long-term goals into smaller steps, and discuss realistic expectations at discharge. Conclusions The results of this study have the potential to contribute to the refinement of pain treatments more broadly. At their core, they suggest that pain treatments should be disseminated more, flexible, and transparent.
Simultaneous estimation of the cellular water exchange rate, intracellular volume fraction, and longitudinal relaxation rate in cancer cells

The purpose of the current study was to investigate the feasibility of simultaneously estimating the cellular water efflux rate ( kie ), intracellular longitudinal relaxation rate ( R10i ), and intracellular volume fraction ( vi ) of a cell suspension using multiple samples with different gadolinium concentrations. Numerical simulation studies were conducted to assess the uncertainty in the estimation of kie , R10i , and vi from saturation recovery data using single (SC) or multiple concentrations (MC) of gadolinium‐based contrast agent (GBCA). In vitro experiments with 4 T1 murine breast cancer and SCCVII squamous cell cancer models were conducted at 11 T to compare parameter estimation using the SC protocol with that using the MC protocol. The cell lines were challenged with a Na+/K+‐ATPase inhibitor, digoxin, to assess the treatment response in terms of kie , R10i , and vi . Data analysis was conducted using the two‐compartment exchange model for parameter estimation. The simulation study data demonstrate that the MC method, compared with the SC method, reduces the uncertainty of the estimated kie by decreasing the interquartile ranges from 27.3% ± 3.7% to 18.8% ± 5.1% and the median differences from ground truth from 15.0% ± 6.3% to 7.2% ± 4.2%, while estimating R10i and vi simultaneously. In the cell studies, the MC method demonstrated reduced uncertainty in overall parameter estimation compared with the SC approach. MC method‐measured parameter changes in cells treated with digoxin increased R10i by 11.7% (p = 0.218) and kie by 5.9% (p = 0.234) for 4 T1 cells, respectively, and decreased R10i by 28.8% (p = 0.226) and kie by 1.6% (p = 0.751) for SCCVII cells, respectively. vi did not change noticeably by the treatment. The results of this study substantiate the feasibility of using saturation recovery data of multiple samples with different GBCA concentrations for simultaneous measurement of the cellular water efflux rate, intracellular volume fraction, and intracellular longitudinal relaxation rate in cancer cells.
Mechanisms underlying the effect of voluntary running on adult hippocampal neurogenesis

Adult hippocampal neurogenesis is important for preserving learning and memory‐related cognitive functions. Physical exercise, especially voluntary running, is one of the strongest stimuli to promote neurogenesis and has beneficial effects on cognitive functions. Voluntary running promotes exit of neural stem cells (NSCs) from the quiescent stage, proliferation of NSCs and progenitors, survival of newborn cells, morphological development of immature neuron, and integration of new neurons into the hippocampal circuitry. However, the detailed mechanisms driving these changes remain unclear. In this review, we will summarize current knowledge with respect to molecular mechanisms underlying voluntary running‐induced neurogenesis, highlighting recent genome‐wide gene expression analyses. In addition, we will discuss new approaches and future directions for dissecting the complex cellular mechanisms driving change in adult‐born new neurons in response to physical exercise.
Antibacterial Potent of Acetylated and Non‐Acetylated Clove Bud Essential Oils and Their Main Compounds

Clove bud is a medicinal plant used traditionally in Asia for the treatment of various disease. Previously, Clove oil is a potential source of an antimicrobial compounds especially vis‐a‐vis bacterial pathogens. However, the compound responsible for this activity remains to be investigated. Essential oil (EO) clove, acetylated essential oil clove, eugenol, and acetyleugenol were evaluate as an antibacterial potential agent against Staphyloccocus aureus (SE), Escherichia coli (EC) and Pseudomonas aeruginosa (PA). Essential oil containing eugenol was extracted from buds of Eugenia caryophyllata commonly named clove (Syzygium aromaticum (L.) (Family Myrtaceae) by a simple hydrodistillation. The analysis of the essential oils (EOs) using gas chromatography‐mass spectrometry (GC‐MS) shows eugenol as the major constituent with 70.14 % of the total. The Eugenol was isolated from the EO using chemical treatment. Afterwards, the EO and eugenol were converted to acetylated EO and acetyleugenol, respectively using acetic anhydride. The antibacterial result revealed that all compounds showed a strong activity against the three strains. The Staphyloccocus aureus and Pseudomonas aeruginosa were extremely sensitive against eugenol with an inhibition diameters of 25 mm. The MIC values of eugenol versus S. aureus and P. aeruginosa were 0.58 and 2.32 mg/mL, respectively, while the MIB values were 2.32 mg/mL and 9.28 mg/mL.
Pulsed photothermal modeling of layered materials

Exact analytical solutions of the heat‐diffusion problem encountered in the pulsed photothermal evaluation of layered materials are presented. The analysis relates to the long‐time decay of the front face temperature following the absorption of a surface heat pulse. The configuration of a coating on a substrate is analyzed, and the parameters governing the temperature evolution are identified with a particular emphasis on the thermal contact resistance term. This model provides a new method of measuring the quality of the interface. Previously published data and new experiments with laminated materials and living tissues are analyzed using the proposed analytical solutions.
Evaluation of Computer-Aided Detection During Colonoscopy in the Community (AI-SEE): A Multicenter Randomized Clinical Trial

INTRODUCTION: There has been increasing interest in artificial intelligence in gastroenterology. To reduce miss rates during colonoscopy, there has been significant exploration in computer-aided detection (CADe) devices. In this study, we evaluate the use of CADe in colonoscopy in community-based, nonacademic practices. METHODS: Between September 28, 2020, and September 24, 2021, a randomized controlled trial (AI-SEE) was performed evaluating the impact of CADe on polyp detection in 4 community-based endoscopy centers in the United States Patients were block-randomized to undergoing colonoscopy with or without CADe (EndoVigilant). Primary outcomes measured were adenomas per colonoscopy and adenomas per extraction (the percentage of polyps removed that are adenomas). Secondary end points included serrated polyps per colonoscopy; nonadenomatous, nonserrated polyps per colonoscopy; adenoma and serrated polyp detection rates; and procedural time. RESULTS: A total of 769 patients were enrolled (387 with CADe), with similar patient demographics between the 2 groups. There was no significant difference in adenomas per colonoscopy in the CADe and non-CADe groups (0.73 vs 0.67, P = 0.496). Although the use of CADe did not improve identification of serrated polyps per colonoscopy (0.08 vs 0.08, P = 0.965), the use of CADe increased identification of nonadenomatous, nonserrated polyps per colonoscopy (0.90 vs 0.51, P < 0.0001), resulting in detection of fewer adenomas per extraction in the CADe group. The adenoma detection rate (35.9 vs 37.2%, P = 0.774) and serrated polyp detection rate (6.5 vs 6.3%, P = 1.000) were similar in the CADe and non-CADe groups. Mean withdrawal time was longer in the CADe group compared with the non-CADe group (11.7 vs 10.7 minutes, P = 0.003). However, when no polyps were identified, there was similar mean withdrawal time (9.1 vs 8.8 minutes, P = 0.288). There were no adverse events. DISCUSSION: The use of CADe did not result in a statistically significant difference in the number of adenomas detected. Additional studies are needed to better understand why some endoscopists derive substantial benefits from CADe and others do not. ClinicalTrials.gov number: NCT04555135.
Comparative evaluation of PD‐L1 expression in cytology imprints, circulating tumour cells and tumour tissue in non‐small cell lung cancer patients

Alternative sources of tumour information need to be explored in patients with non‐small cell lung cancer (NSCLC). Here, we compared programmed cell death ligand 1 (PD‐L1) expression on cytology imprints and circulating tumour cells (CTCs) with PD‐L1 tumour proportion score (TPS) from immunohistochemistry staining of tumour tissue from patients with NSCLC. We evaluated PD‐L1 expression using a PD‐L1 antibody (28‐8) in representative cytology imprints, and tissue samples from the same tumour. We report good agreement rates on PD‐L1 positivity (TPS ≥ 1%) and high PD‐L1 expression (TPS ≥ 50%). Considering high PD‐L1 expression, cytology imprints showed a PPV of 64% and a NPV of 85%. CTCs were detected in 40% of the patients and 80% of them were PD‐L1+. Seven patients with PD‐L1 expression of < 1% in tissue samples or cytology imprints had PD‐L1+ CTCs. The addition of PD‐L1 expression in CTCs to cytology imprints markedly improved the prediction capacity for PD‐L1 positivity. A combined analysis of cytological imprints and CTCs provides information on the tumoural PD‐L1 status in NSCLC patients, which might be used when no tumor tissue is available.
The effect of COVID-19 vaccine tele-educational program on vaccine hesitancy and receiving the vaccine among women planning for pregnancy, pregnant or breast-feeding mothers

Background COVID-19 hesitancy among women planning to become pregnant, who are pregnant, and who are breast-feeding is still a global phenomenon. Unfortunately, there is a lack of national educational programs that provide those groups of people with the information they need about the vaccine. Objective This study investigated the effect of the COVID-19 vaccine tele-educational program on vaccine hesitancy and receiving the vaccine among women planning for pregnancy, pregnant and breast-feeding mothers. Methods This study implemented a quasi-experimental pre-post design and was conducted in Jordan. It was a two-time study and had two groups of women; 220 women participated in the control group, and 205 women participated in the intervention group (those received the tele-educational program). All participating women answered the demographic characteristics sheet and the Arabic version of Hesitancy About COVID-19 Vaccination Questionnaire twice. Results Results showed that after conducting the program the interventional group reported significantly higher vaccination rate and lower mean score of hesitancy than the control group (M = 24.67, SD = 5.11; M = 27.45, SD = 4.92; respectively) t (423) = -4.116, p-value < 0.001. Moreover, before the program, women in the intervention group reported significantly higher levels of hesitancy compared to those in the same group after the program (M = 28.35, SD = 4.91; M = 24.66, SD = 5.11; respectively) t (204) = 17.83, p-value < 0.001. Conclusions The study concluded that awareness of pregnant women after being given the tele-education program about COVID-19 vaccination decreased their hesitancy and improved their willingness to participate in the COVID-19 vaccination. Therefore, health workers should focus on providing scientific-based information about the vaccine to reduce the doubts of pregnant women about participating in the COVID-19.