Miracle-dz/UniFAR-FTUs huggingface dataset:
Preparation and Characterization of Moldable Demineralized Bone Matrix/Calcium Sulfate Composite Bone Graft Materials

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO4, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and β-form of calcium sulfate hemihydrate (CaSO4·0.5H2O, CSH) were produced by heating gypsum (CaSO4·2H2O). The morphology and particle sizes of α- and β-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or β-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler.
Baseline Subfoveal Choroidal Thickness as a Predictor for Response to Short-Term Intravitreal Bevacizumab Injections in Diabetic Macular Edema

Purpose This article aims to evaluate how the subfoveal choroidal thickness (SFCT) and best-corrected visual acuity (BCVA) respond to the intravitreal injection of bevacizumab and to assess the correlation between these changes. It will also assess the use of the baseline SFCT as a predictor for BCVA changes in eyes of treatment-naive, diabetic macular edema (DME) patients. Methods This retrospective, consecutive case series comprised 59 eyes of 39 treatment-naive DME patients. Complete slit-lamp assessment, swept-source optical coherence tomography (SS-OCT) scans to measure SFCT and BCVA values were performed at two stages: baseline and one month after the third monthly injection of intravitreal bevacizumab. Results Patients’ ages ranged from 46.3 to 76.4 years (mean: 62.6 ± 2.3). The mean SFCT was 318 ± 82 μm at baseline, which decreased after 3 months to 300 ± 66 μm (P-value = 0.021). There was an improvement in the mean of the logMAR best-corrected visual acuity (BCVA) from 0.7 (decimal equivalent: 0.2) to 0.5 (decimal equivalent: 0.3) (P-value = 0.019). There was no association between SFCT changes and BCVA changes (P-value = 0.180). Wilcoxon signed-rank test disclosed that a better BCVA improvement was related to a greater subfoveal choroidal thickness at baseline P-value <0.00. Conclusion Eyes with a higher baseline subfoveal choroidal thickness (SFCT) attained greater BCVA improvement than eyes with a lower baseline SFCT. In addition to this, changes to SFCT do not appear to correlate with BCVA changes. These findings do not support using OCT SFCT changes as a prognostic factor for changes to BCVA after intravitreal bevacizumab treatment in evaluating treatment-naive DME eyes.
Teleprogramming Service Provides Safe and Remote Stimulation Options for Patients with DRG-S and SCS Implants

Background Chronic pain patients implanted with a neurostimulation device typically require follow-up and device programming visits to address changes in symptoms or treatment. Follow-up visits require access to specialty care and necessitate patients to take time off work, commute long distances, arrange for travel, and/or work with a caregiver’s schedule. Telemedicine was adopted for some patient management as a result of the Sars-Cov-2 pandemic; however, remote optimization for neuromodulation still required an in-person visit to adjust device parameters. An FDA-approved digital platform enables remote programming of an implanted neuromodulation device using a real-time audio-video link from the clinical programmer to the patient controller. The Remote Optimization, Adjustment, and Measurement for Chronic Pain Therapy (ROAM-CPT) is a multi-center, prospective study that is currently underway to access the effectiveness of the teleprogramming system in fulfilling patients’ clinical demands. Methods This pilot study surveyed 16 patients to determine the ability of the teleprogramming platform to provide a rapid solution safely and effectively for patient’s chronic pain. Data were collected using a questionnaire that asked 6 clinician-centric questions and 5 patient-centric questions. Results 4/4 surveyed physicians were able to address patients’ needs. 16/16 surveyed patients reported a quick resolution to pain and 15/16 did not require additional follow-up. Data curated from this pilot study show that the teleprogramming application greatly improves patient care, is preferred by both clinicians and patients with minimal disruptions to patients’ everyday lives. Conclusion Teleprogramming provides real-time virtual programming capabilities and optimizes patients’ therapy. Perspective This article describes remote device programming and analysis as an alternative to in-person programming/treatment sessions for neuromodulation patients. This remote option gives patients access to timely and clinically appropriate device management when in-person care may not be available.
Clinically Distinct Subtypes of Acute Kidney Injury on Hospital Admission Identified by Machine Learning Consensus Clustering

Background: We aimed to cluster patients with acute kidney injury at hospital admission into clinically distinct subtypes using an unsupervised machine learning approach and assess the mortality risk among the distinct clusters. Methods: We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 4289 hospitalized adult patients with acute kidney injury at admission. The standardized difference of each variable was calculated to identify each cluster’s key features. We assessed the association of each acute kidney injury cluster with hospital and one-year mortality. Results: Consensus clustering analysis identified four distinct clusters. There were 1201 (28%) patients in cluster 1, 1396 (33%) patients in cluster 2, 1191 (28%) patients in cluster 3, and 501 (12%) patients in cluster 4. Cluster 1 patients were the youngest and had the least comorbidities. Cluster 2 and cluster 3 patients were older and had lower baseline kidney function. Cluster 2 patients had lower serum bicarbonate, strong ion difference, and hemoglobin, but higher serum chloride, whereas cluster 3 patients had lower serum chloride but higher serum bicarbonate and strong ion difference. Cluster 4 patients were younger and more likely to be admitted for genitourinary disease and infectious disease but less likely to be admitted for cardiovascular disease. Cluster 4 patients also had more severe acute kidney injury, lower serum sodium, serum chloride, and serum bicarbonate, but higher serum potassium and anion gap. Cluster 2, 3, and 4 patients had significantly higher hospital and one-year mortality than cluster 1 patients (p < 0.001). Conclusion: Our study demonstrated using machine learning consensus clustering analysis to characterize a heterogeneous cohort of patients with acute kidney injury on hospital admission into four clinically distinct clusters with different associated mortality risks.
Psychological impact of COVID-19 and contributing factors of students’ preventive behavior based on HBM in Gondar, Ethiopia

Background The Ethiopian Federal government has locked down schools as one measure to contain Covid-19 pandemic. Psychological effect of COVID-19 on students is increased due to the reopening of schools. The psychological effect of the pandemic is increasing along with physical aspect of health. Therefore, this study aimed to assess the psychological impact of Covid-19 and its contributing factors of students’ behavior in Ethiopia. Methods A cross sectional design was conducted from November to December 2020. Data were collected using pre tested self- administered questionnaire from secondary school students in Gondar city North West Ethiopia. Stratified simple random sampling technique was used to select 403 secondary school students. Data were entered and cleaned with Epidata version 4.62 and exported for analysis STATA version 14. Multivariable logistic regression and multiple linear regression were used to show the association of dependent and independent variables. Independent variables in relation to dependent variable measured using odd ratios and B coefficient with 95% confidence interval for Covid-19 anxiety and preventive behavior of Covid-19 respectively were used. Results A total of 370 students were participated giving response rate of 92%. The prevalence of Covid-19 anxiety and obsession among secondary school students were 38.1% and 40.27% respectively. Being 11thgrade 54% (AOR = 0.46; 95%CI:0.22, 0.95) and increased knowledge16% (AOR = 0.84;95%CI: 0.77, 0.89) score associated with decreased COVID-19 anxiety while Covid-19 obsession, 14.51 times (AOR = 14.51;95%CI: 8.05, 26.17), and being female 1.6 times (AOR = 1.6; 95%CI: 1.01, 2.51) increased Covid-19 Anxiety. Furthermore, increased self-efficacy 0.5 times (B = 0.5; 95%CI: 0.28, 0.62), and increased cues to action 0.4 times (B = 0.4; 95% CI: 0.19, 0.69) increased preventive behavior of Covid-19 while perceived barrier 0.1 times (B = -0.1; 95%CI:-0.22, 0.01) decrease preventive behavior of Covid-19. Conclusion Almost two individuals of five participants developed COVID-19 anxiety and COVID-19 obsession. Being grade 11th and knowledge were negatively associated with anxiety while being female and being obsessed with COVID-19 were positively associated with anxiety. No variable was associated with obsession of Covid-19. Intervention is needed to reduce anxiety among females. Furthermore, perceived barrier, self-efficacy and cues to action were significant factors of preventive behaviour of Covid-19. Therefore, to increase preventive behaviour of Covid-19, information, education and communication and behavioural change communication should be targeted on reducing barriers and increasing motivations and confidences.
Comparison of Autistic Individuals Who Engage in Self-Injurious Behavior, Aggression, and Both Behaviors

Background. Two of the most challenging behaviors exhibited by individuals on the autism spectrum are self-injurious behavior (SIB) and aggression. The aim of this study was to identify co-occurring symptoms, behaviors, and medical comorbidities that may provide insight into understanding and treating these behaviors. Method. A large-scale online survey was used to collect data on symptoms, behaviors, and medically related comorbidities commonly reported in individuals with autism spectrum disorders (ASD). Based on responses from 2327 participants, individuals with ASD were divided into four categories: individuals who engaged in SIB only, individuals who engaged in aggression only, individuals who engaged in both behaviors, and individuals who engaged in neither behavior. Results. There were several characteristics and comorbidities associated with those who engaged in SIB only and in aggression only, in addition to those who engaged in both behaviors. Conclusion. The findings in this study provide evidence to support at least two underlying causes of these behaviors (insensitivity to pain and reactions to food) as well as implications for treating them. Furthermore, several behaviors often observed during early childhood may be considered early predictors of these challenging behaviors.
Formulation and In-Vitro Characterization of pH-Responsive Semi-Interpenetrating Polymer Network Hydrogels for Controlled Release of Ketorolac Tromethamine

Ketorolac tromethamine is a non-steroidal anti-inflammatory drug used in the management of severe pain. The half-life of Ketorolac tromethamine is within the range of 2.5–4 h. Hence, repeated doses of Ketorolac tromethamine are needed in a day to maintain the therapeutic level. However, taking several doses of Ketorolac tromethamine in a day generates certain complications, such as acute renal failure and gastrointestinal ulceration. Therefore, a polymeric-controlled drug delivery system is needed that could prolong the release of Ketorolac tromethamine. Therefore, in the current study, pH-responsive carbopol 934/sodium polystyrene sulfonate-co-poly(acrylic acid) (CP/SpScPAA) hydrogels were developed by the free radical polymerization technique for the controlled release of Ketorolac tromethamine. Monomer acrylic acid was crosslinked with the polymers carbopol 934 and sodium polystyrene sulfonate by the cross-linker N’,N’-methylene bisacrylamide. Various studies were conducted to evaluate and assess the various parameters of the fabricated hydrogels. The compatibility of the constituents used in the preparation of hydrogels was confirmed by FTIR analysis, whereas the thermal stability of the unreacted polymers and developed hydrogels was analyzed by TGA and DSC, respectively. A smooth and porous surface was indicated by SEM. The crystallinity of carbopol 934, sodium polystyrene sulfonate, and the prepared hydrogels was evaluated by PXRD, which revealed a reduction in the crystallinity of reactants for the developed hydrogels. The pH sensitivity of the polymeric hydrogel networks was confirmed by dynamic swelling and in vitro release studies with two different pH media i.e., pH 1.2 and 7.4, respectively. Maximum swelling was exhibited at pH 7.4 compared to pH 1.2 and, likewise, a greater percent drug release was perceived at pH 7.4. Conclusively, we can demonstrate that the developed pH-sensitive hydrogel network could be employed as a suitable carrier for the controlled delivery of Ketorolac tromethamine.
Multiplexed DNA Methylation Analysis in Colorectal Cancer Using Liquid Biopsy and Its Diagnostic and Predictive Value

Early diagnosis of colorectal cancer (CRC) is of high importance as prognosis depends on tumour stage at the time of diagnosis. Detection of tumour-specific DNA methylation marks in cfDNA has several advantages over other approaches and has great potential for solving diagnostic needs. We report here the identification of DNA methylation biomarkers for CRC and give insights in our methylation-sensitive restriction enzyme coupled qPCR (MSRE-qPCR) system. Targeted microarrays were used to investigate the DNA methylation status of 360 cancer-associated genes. Validation was done by qPCR-based approaches. A focus was on investigating marker performance in cfDNA from 88 patients (44 CRC, 44 controls). Finally, the workflow was scaled-up to perform 180plex analysis on 110 cfDNA samples, to identify a DNA methylation signature for advanced colonic adenomas (AA). A DNA methylation signature (n = 44) was deduced from microarray experiments and confirmed by quantitative methylation-specific PCR (qMSP) and by MSRE-qPCR, providing for six genes’ single areas under the curve (AUC) values of >0.85 (WT1, PENK, SPARC, GDNF, TMEFF2, DCC). A subset of the signatures can be used for patient stratification and therapy monitoring for progressed CRC with liver metastasis using cfDNA. Furthermore, we identified a 35-plex classifier for the identification of AAs with an AUC of 0.80.
Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes

Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine Opn4KO melanocytes displayed a faster proliferation rate compared to Opn4WT melanocytes. Cell cycle population analysis demonstrated that OPN4KO melanocytes exhibited a faster cell cycle progression with reduced G0–G1, and highly increased S and slightly increased G2/M cell populations compared to the Opn4WT counterparts. Expression of specific cell cycle-related genes in Opn4KO melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in Opn4KO melanocytes compared to Opn4WT cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in Opn4KO melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.
IPM reduces insecticide applications by 95% while maintaining or enhancing crop yields through wild pollinator conservation

Significance Environmental damage from insecticide overuse is a major concern, particularly for conservation of “good” insects such as pollinators that ensure stable production of food crops like fruits and vegetables. However, insecticides are also necessary for farmers to manage “bad” insects (i.e., pests), and thus, a more holistic view of crop management needs to account for the proper balance between the beneficial and detrimental aspects of pesticides. Here, we used multiyear field experiments with a paired corn–watermelon cropping system to show that insecticide use can be dramatically reduced (by ∼95%) while maintaining or even increasing yields through the conservation of wild bees as crop pollinators. These data demonstrate that food production and ecosystem sustainability are not necessarily conflicting goals. Pest management practices in modern industrial agriculture have increasingly relied on insurance-based insecticides such as seed treatments that are poorly correlated with pest density or crop damage. This approach, combined with high invertebrate toxicity for newer products like neonicotinoids, makes it challenging to conserve beneficial insects and the services that they provide. We used a 4-y experiment using commercial-scale fields replicated across multiple sites in the midwestern United States to evaluate the consequences of adopting integrated pest management (IPM) using pest thresholds compared with standard conventional management (CM). To do so, we employed a systems approach that integrated coproduction of a regionally dominant row crop (corn) with a pollinator-dependent specialty crop (watermelon). Pest populations, pollination rates, crop yields, and system profitability were measured. Despite higher pest densities and/or damage in both crops, IPM-managed pests rarely reached economic thresholds, resulting in 95% lower insecticide use (97 versus 4 treatments in CM and IPM, respectively, across all sites, crops, and years). In IPM corn, the absence of a neonicotinoid seed treatment had no impact on yields, whereas IPM watermelon experienced a 129% increase in flower visitation rate by pollinators, resulting in 26% higher yields. The pollinator-enhancement effect under IPM management was mediated entirely by wild bees; foraging by managed honey bees was unaffected by treatments and, overall, did not correlate with crop yield. This proof-of-concept experiment mimicking on-farm practices illustrates that cropping systems in major agricultural commodities can be redesigned via IPM to exploit ecosystem services without compromising, and in some cases increasing, yields.
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Coadministered Ruxolitinib and Artemether-Lumefantrine in Healthy Adults

Despite repeated malaria infection, individuals living in areas where malaria is endemic remain vulnerable to reinfection. The Janus kinase (JAK1/2) inhibitor ruxolitinib could potentially disrupt the parasite-induced dysfunctional immune response when administered with antimalarial therapy. ABSTRACT Despite repeated malaria infection, individuals living in areas where malaria is endemic remain vulnerable to reinfection. The Janus kinase (JAK1/2) inhibitor ruxolitinib could potentially disrupt the parasite-induced dysfunctional immune response when administered with antimalarial therapy. This randomized, single-blind, placebo-controlled, single-center phase 1 trial investigated the safety, tolerability, and pharmacokinetic and pharmacodynamic profile of ruxolitinib and the approved antimalarial artemether-lumefantrine in combination. Ruxolitinib pharmacodynamics were assessed by inhibition of phosphorylation of signal transducer and activator of transcription 3 (pSTAT3). Eight healthy male and female participants ages 18 to 55 years were randomized to either ruxolitinib (20 mg) (n = 6) or placebo (n = 2) administered 2 h after artemether-lumefantrine (80/480 mg) twice daily for 3 days. Mild adverse events occurred in six participants (four ruxolitinib; two placebo). The combination of artemether-lumefantrine and ruxolitinib was well tolerated, with adverse events and pharmacokinetics consistent with the known profiles of both drugs. The incidence of adverse events and artemether, dihydroartemisinin (the major active metabolite of artemether), and lumefantrine exposure were not affected by ruxolitinib coadministration. Ruxolitinib coadministration resulted in a 3-fold-greater pSTAT3 inhibition compared to placebo (geometric mean ratio = 3.01 [90% confidence interval = 2.14 to 4.24]), with a direct and predictable relationship between ruxolitinib plasma concentrations and %pSTAT3 inhibition. This study supports the investigation of the combination of artemether-lumefantrine and ruxolitinib in healthy volunteers infected with Plasmodium falciparum malaria. (This study has been registered at ClinicalTrials.gov under registration no. NCT04456634.)
Multidisciplinary participation: The key to a cure for non‐alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide and induces enormous burden on societies. One landmark review highlighted the critical need for the multidisciplinary models of care for patients with NAFLD, firstly proposing a clinical pathway regarding the management of cardiometabolic complications in NAFLD. In this article, we discussed the specific functions and importance of multidisciplinary working group members (such as dietitians, exercise physiotherapists, hepatologists, endocrinologists, and cardiovascular experts) and call on the different healthcare professionals to orchestrate together to address the growing burden of NAFLD.
Non-use of telemedicine: A scoping review

Many telemedicine interventions fail to be implemented in medical care with non-use and discontinued use by patients being among the major reasons. The aim of this scoping review was to provide an overview of barriers associated with non-use and discontinued use of telemedicine. An electronic search was conducted in Pubmed in October 2019 and updated in November 2020, followed by a hand search in the beginning of 2021. All potential articles were screened by two independent reviewers based on predefined inclusion and exclusion criteria. A qualitative content analysis according to Mayring was carried out. The topics ‘intervention’, ‘context of use’ and ‘user’ were chosen as overarching themes. Out of 1377 potentially relevant articles, 73 were included. User-related barriers were mentioned in most of the analysed studies, followed by barriers related to the intervention. The analysis provides the basis for overcoming non-use issues in telemedicine.