Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects and Processes of an mHealth Intervention for the Management of Chronic Diseases: Prospective Observational Study

Background Mobile health (mHealth) interventions for self-management are a promising way to meet the needs of patients with chronic diseases in primary care practices. Therefore, an mHealth intervention, TelePraCMan, was developed and evaluated for patients with type 2 diabetes mellitus, chronic obstructive pulmonary disease, high blood pressure, or heart failure in a German primary care setting. TelePraCMan entails a symptom diary, an appointment manager, a manager to document goals, and a warning system. The app should foster the self-management of participating patients. Objective We aimed to examine the effects of TelePraCMan on patient activation and quality of life and explored the underlying contextual factors, impacts, and degree of implementation. Methods In a prospective observational study design, we collected data by using interviews and written questionnaires from participating patients (intervention and control groups) and primary care workers (physicians and practice assistants). The primary outcomes of interest were patient-reported quality of life (12-Item Short Form Survey) and patient activation (patient activation measure). The quantitative analysis focused on differences between patients in the intervention and control groups, as well as before (T0) and after (T1) the intervention. Interviews were analyzed by using qualitative content analysis via MAXQDA (VERBI GmbH). Results At baseline, 25 patients and 24 primary care workers completed the questionnaire, and 18 patients and 21 primary care workers completed the follow-up survey. The patients were predominantly male and, on average, aged 64 (SD 11) years (T0). The primary care workers were mostly female (62%) and, on average, aged 47 (SD 10) years (T0). No differences were observed in the outcomes before and after the intervention or between the intervention and control groups. In the additional interviews, 4 patients and 11 primary care workers were included. The interviewees perceived that the intervention was useful for some patients. However, contextual factors and problems with implementation activities negatively affected the use of the app with patients. The main reasons for the low participation were the COVID-19 pandemic and the target group, which seemed to have less interest in mHealth; the interviewees attributed this to the older age of patients. However, the respondents felt that the app would be better accepted in 5 or 10 years. Conclusions Although the TelePraCMan app was rated as very good and important by the participants, few patients used it. The digital intervention was hardly implemented and had limited impact in the current setting of German primary care. Trial Registration German Clinical Trials Register DRKS00017320; https://tinyurl.com/4uwrzu85
Articulative labor in assembling protest networks in the disjointed WeChatsphere: Rethinking human and non-human agency in digitally mediated activism

Recent scholarship indicates that the rise of networked grassroots protests points to a new mode of organizing activism, connective action. Unlike social movement organization-led collective actions, connective actions are organized by non-human agents – digital networks and platforms – because of the latter’s inherent connectivity in assembling people, information and resources scattered across digital spaces into relatively cohesive protest networks. Yet, not all digital platforms are designed to afford unlimited connections; ‘walled gardens’ and proprietary systems disconnect more than connecting. WeChat, a China-based social media platform, spearheads in engineering an enclosed digital ecosystem, due to China’s political economy. How can protest networks develop in such an insulated environment? This study examines a WeChat-based protest campaign organized mainly by Chinese Americans to illustrate the organizing dynamics on disconnected platforms. Relying on interviews, observation and textual analysis, the findings show that WeChat, instead of acting as a non-human organizer, disorganized the mobilization by impeding the free flow of information and resources. To head off the platform-led barriers, activists performed articulative labor to cross boundaries, bridge gaps and broker resources, which finally articulated the protest network in this digitally disconnective environment. As contemporary digital landscapes become increasingly fragmented, this study not only sheds light on the significant yet hidden articulative labor in networked activism but also prompts us to rethink connective action and other technological deterministic models’ valorization of non-human agency and to reconsider the relationship of human and non-human agency in constituting collective actions and sociality in general.
Preferential Antibody and Drug Conjugate Targeting of the ADAM10 Metalloprotease in Tumours

Simple Summary ADAM10 is a cell surface protein that releases other proteins from cells, thereby controlling a range of functions during normal development. Its activity is normally tightly regulated, but it can become deregulated in cancer calls. We previously showed that an active form of ADAM10 is elevated in tumours in both mice and humans, and that we could detect this active form using an antibody which we developed that binds to a specific region of ADAM10, which is apparently hidden in the inactive form. We now provide insight explaining the specificity of our antibody (8C7) for active ADAM10, and show that it preferentially targets tumours when injected into mice. We thus conjugated cytotoxic drugs to 8C7 in order to preferentially bind and kill tumour cells that contain activated ADAM10. Our experiments show that our ‘8C7 antibody–drug conjugates’ specifically kill cells expressing 8C7-reactive ADAM10, and can inhibit the growth of tumours in mice, without significant side effects, suggesting their potential as a novel approach for targeted cancer therapy. Abstract ADAM10 is a transmembrane metalloprotease that sheds a variety of cell surface proteins, including receptors and ligands that regulate a range of developmental processes which re-emerge during tumour development. While ADAM10 is ubiquitously expressed, its activity is normally tightly regulated, but becomes deregulated in tumours. We previously reported the generation of a monoclonal antibody, 8C7, which preferentially recognises an active form of ADAM10 in human and mouse tumours. We now report our investigation of the mechanism of this specificity, and the preferential targeting of 8C7 to human tumour cell xenografts in mice. We also report the development of novel 8C7 antibody–drug conjugates that preferentially kill cells displaying the 8C7 epitope, and that can inhibit tumour growth in mice. This study provides the first demonstration that antibody–drug conjugates targeting an active conformer of ADAM10, a widely expressed transmembrane metalloprotease, enable tumour-selective targeting and inhibition.
Industrialization as a Deskilling Process? Steam Engines and Human Capital in XIXth Century France

Was technological progress conducive to human capital accumulation or was industrialization a deskilling process? Our paper investigates the effect of the French industrialization process on human capital accumulation throughout the nineteenth century. The novelty of the research is twofold: (i) we explore the deskilling hypothesis for the whole process of industrialization by implementing a panel analysis; (ii) we introduce a disaggregated human capital perspective to examine changes in skills demand at different stages of the process. Our analysis builds upon a new comprehensive dataset providing an exhaustive assessment of the diffusion of the steam technology in France at the county (Departement) level over the 1839-1900 period. We use exogenous geographic variations as an instrument for the number of steam engines erected in each French department. We perform panel and cross-section regression analyses to compare the effect of technological change on basic vs. intermediate human capital accumulation. Our contribution reveals that French industrialization was not deskilling but that a shift in the type of the skills demanded occurred in the second half on the nineteenth century.
Antisalmonella Potency of Varying Extracts of Garcinia kola

Plants are a source of first-line treatment for most humans, particularly in Africa and offer nutrition for most terrestrial ecosystems. The world's attention have been called repeatedly to the therapeutic marvels of plants, one of which is Garcinia kola. This study aims to determine the antisalmonella efficacy of several Garcinia kola leaf and seed extracts. Extracts of leaves, seeds, and seed/leaf were obtained using methanol and ethanol as extraction solvents. Inoculated Salmonella typhi were observed for 24 hours using the well diffusion method to determine zones of inhibition. All extracts were found to be effective against S. typhi. 100/50 mg/ml methanol leave extract produced a 14/12mm zone of inhibition, whereas 100/50 mg/ml methanol seed extract produced a 13/11mm zone of inhibition. 100/50 mg/ml ethanol leave extract showed a 17/10mm inhibition zone, while 100/50 mg/ml ethanol seed extract showed a 16/14mm inhibition zone. The inhibition zone of methanol seed/leaf extract of 100/50 mg/ml was 17/12mm, while the inhibition zone of ethanol seed/leaf extract was 19/14mm. While all concentrations of plant extracts were effective against S. typhi, greater concentrations created larger zones of inhibition and the plant extracts outperformed the control. Seed/leaf extracts outperformed seed extract and leaf extract in most cases. The results showed that ethanol was a better extraction liquid and that the leaf extracts were more potent; however, this is not true in all cases. To stimulate local mitigation of illnesses caused by Salmonella typhi, more research on the antisalmonella effectiveness of Garcinia kola seed and leaf extracts should be done.
Optimization of Ultrasound-Assisted Extraction of Yields and Total Methoxyflavone Contents from Kaempferia parviflora Rhizomes

The major bioactive components of Kaempferia parviflora (KP) rhizomes, 3,5,7,3′,4′-pentamethoxyflavone (PMF), 5,7-dimethoxyflavone (DMF), and 5,7,4′-trimethoxyflavone (TMF), were chosen as the quantitative and qualitative markers for this plant material. In order to extract bioactive components (total methoxyflavones) from KP rhizomes, ultrasound-assisted extraction (UAE) was proposed as part of this study. Plackett–Burman design (PBD) and Box–Behnken design (BBD) were utilized to optimize the effects of UAE on extraction yields and total methoxyflavone contents in KP rhizomes. First, PBD was utilized to determine the effect of five independent variables on total yields and total methoxyflavone contents. The results indicated that the concentration of the extracting solvent (ethanol), the extraction time, and the ratio of solvent to solid were significant independent terms. Subsequently, BBD with three-level factorial experiments was used to optimize the crucial variables. It was discovered that the concentration of ethanol was the most influential variable on yields and total methoxyflavone contents. Optimum conditions for extraction yield were ethanol concentration (54.24% v/v), extraction time (25.25 min), and solvent-to-solid ratio (49.63 mL/g), while optimum conditions for total methoxyflavone content were ethanol concentration (95.00% v/v), extraction time (15.99 min), and solvent-to-solid ratio (50.00 mL/g). The relationship between the experimental and theoretical values was perfect, which proved that the regression models used were correct and that PBD and BBD were used to optimize the conditions in the UAE to obtain the highest yield and total methoxyflavone content in the KP rhizomes.
Azithromycin treatment failure and macrolide resistance in Mycoplasma genitalium infections in Sofia, Bulgaria.

INTRODUCTION Mycoplasmagenitalium is an established cause of sexually transmitted infections in men and women. Current guidelines recommend azithromycin and moxifloxacin as first- and second-line treatment, respectively. However, azithromycin treatment failure has been increasingly reported. The aim of this study was to determine the efficacy of azithromycin and alternative antibiotic regimens in a prospective cohort of M.genitalium-positive patients, and macrolide resistance mutations associated with azithromycin failure.
Meeting the statistical needs of researchers in the biological and health sciences

The results of a survey on the use of statistics in research in five subject areas representative of the biological and health sciences are reported. The main component of the survey is a review of statistical methods in 2927 research papers published during 1999 in 16 high impact journals from botany, ecology, food science, marine science and nutrition. A factor analysis establishes that research papers in the different subject areas use different methods. The opinions of research staff and postgraduate students working in these areas are also reported. To support these opinions we provide details of five postgraduate studies involving advanced statistical analyses, which have either resulted in publication or should result in publication in the near future. Discussion develops recommendations about topics important in a statistics curriculum for research students, where statistics courses should be taught, what is needed in terms of level of theory, the use of short courses and workshops, and the value of project work.
Differential Branchial Response of Low Salinity Challenge Induced Prolactin in Active and Passive Coping Style Olive Flounder

Stress coping styles are very common in fish, and investigations into this area can greatly improve fish welfare and promote the sustainable development of aquaculture. Although most studies have focused on the behavioral and physiological differences of these fishes, the endocrine response of different coping styles fish when undergoing salinity challenge is still unclear. We examined the physiological response in olive flounder with active coping (AC) style and passive coping (PC) style after transferred from seawater (SW) to freshwater for 0, 2, 5, 8, and 14 days. The results showed that: 1) the plasma prolactin level of FW-acclimated AC flounder was substantially higher than that of FW-acclimated PC flounder at 5, 8, and 14 days, and the branchial gene expression of prolactin receptor (PRLR) in AC flounder was slightly higher than PC flounder after transfer. While there was no remarkable difference observed in cortisol (COR) levels between AC and PC flounder. After transfer, glucocorticoid receptor (GR) expression in AC flounder was significantly higher compared with PC flounder at 8 days. 2) Branchial NKA-IR ionocytes numbers were reduced in PC flounder after transfer, while ionocytes number remain stable in AC flounder. 3) The branchial stem cell transcription factor foxi1 gene expression of AC flounder was significantly higher than PC flounder at 2, 5, and 14 days after transfer, while branchial stem cell transcription factor p63 gene expression of FW-acclimated AC flounder was only substantially higher than that of PC flounder at 5 days. 4) As an apoptosis upstream initiator, the branchial gene expression of caspase-9 in PC flounder was considerably higher than in AC flounder after transfer at 8 days. This study revealed that olive flounder with active and passive coping styles have different endocrine coping strategies after facing the low-salinity challenge. AC flounder adopt an active endocrine strategy by increasing ionocyte differentiation and prolactin secretion significantly. In contrast, PC flounder employ a passive strategy of reducing ionocytes differentiation and retaining prolactin content at a low level to reduce branchial ionocytes number.
Dual PI3K/mTOR Inhibitor NVP-BEZ235 Leads to a Synergistic Enhancement of Cisplatin and Radiation in Both HPV-Negative and -Positive HNSCC Cell Lines

Simple Summary Head and neck cancers (HNSCCs), especially in the advanced stages, are predominantly treated by radiochemotherapy, including cisplatin. The cure rates are clearly higher for HPV-positive HNSCCs when compared to HPV-negative HNSCCs. For both entities, this treatment is accompanied by serious adverse reactions, mainly due to cisplatin administration. We reported earlier that for both HPV-positive and negative HNSCC cells, the effect of radiotherapy was strongly enhanced when pretreated using the dual PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235). The current study shows that for HPV-positive cells, BEZ235 will strongly enhance the effect of cisplatin alone. More important, preincubation with BEZ235 was found to alter the purely additive effect normally seen when cisplatin is combined with radiation into a strong synergistic enhancement. This tri-modal combination might allow for the enhancement of the effect of radiochemotherapy, even with reduced cisplatin. Abstract The standard of care for advanced head and neck cancers (HNSCCs) is radiochemotherapy, including cisplatin. This treatment results in a cure rate of approximately 85% for oropharyngeal HPV-positive HNSCCs, in contrast to only 50% for HPV-negative HNSCCs, and is accompanied by severe side effects for both entities. Therefore, innovative treatment modalities are required, resulting in a better outcome for HPV-negative HNSCCs, and lowering the adverse effects for both entities. The effect of the dual PI3K/mTOR inhibitor NVP-BEZ235 on a combined treatment with cisplatin and radiation was studied in six HPV-negative and six HPV-positive HNSCC cell lines. Cisplatin alone was slightly more effective in HPV-positive cells. This could be attributed to a defect in homologous recombination, as demonstrated by depleting RAD51. Solely for HPV-positive cells, pretreatment with BEZ235 resulted in enhanced cisplatin sensitivity. For the combination of cisplatin and radiation, additive effects were observed. However, when pretreated with BEZ235, this combination changed into a synergistic interaction, with a slightly stronger enhancement for HPV-positive cells. This increase could be attributed to a diminished degree of DSB repair in G1, as visualized via the detection of γH2AX/53BP1 foci. BEZ235 can be used to enhance the effect of combined treatment with cisplatin and radiation in both HPV-negative and -positive HNSCCs.
Symptomatic postoperative spinal epidural hematoma preferentially occurs after anterior cervical discectomy and fusion versus anterior cervical corpectomy and fusion: a retrospective study.

BACKGROUND Cervical spondylotic myelopathy (CSM) is a common cause of neurological morbidity, which can have an impact on quality of life. Symptomatic postoperative spinal epidural hematoma (SPSEH) is a rare condition, but can cause permanent neurological deficits and disability if not managed properly. However, there are limited studies on the outcomes of SPSEH after anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) were performed for 2-level CSM. Therefore, the aim of the present study was to compare the clinical outcomes and incidence of SPSEH after ACDF compared with SPSEH after anterior cervical corpectomy and ACCF for 2-level CSM to reduce surgical complications of 2 level CSM. METHODS A total of 551 patients (261 males and 290 females) who underwent ACDF or ACCF for 2-level CSM from January 2009 to February 2015 were retrospectively reviewed. Preoperative indexes (age, sex, body mass index, bone mineral density, preoperative coagulation, and past medical history), perioperative indexes (length of hospital admission, blood loss, and operation times), preoperative and postoperative neurological statuses, complications, fusion rate, and the SPSEH incidence for ACDF or ACCF were compared simultaneously. RESULTS With the exception of blood loss (P<0.001), no significant differences were observed between the 2 groups in terms of sex, prothrombin time, activated partial thromboplastin time, platelet count, length of hospital admission, operation time, the final follow-up Japanese Orthopedic Association score, visual analog scale score, fusion rate, and complications. The overall incidence rate for SPSEH after ACDF was 1.9%, while the rate for SPSEH after ACCF was 0.4%. Following hematoma removal, only one patient showed any improvement in neurological function, despite treatment with hyperbaric oxygen and neurotrophic drugs. CONCLUSIONS The findings indicated that surgical management of 2-level CSM using ACDF or ACCF showed similar clinical outcomes, fusion rate, complications, and perioperative parameters, with the exception of blood loss. However, SPSEH preferentially occurs after surgery with ACDF. Therefore, whether ACCF surgery for 2-stage CSM is the superior treatment modality.
Comprehensive analysis of mutational profile and prognostic significance of complex glandular pattern in lung adenocarcinoma

Background Complex glandular pattern (CGP) was included as high-grade pattern in the new grading system proposed by The International Association for the Study of Lung Cancer. We aimed to investigate the mutational profile and validate the prognostic significance and proper cut-off value to distinguish the aggressive behavior of CGP. Methods CGP was defined as nests of tumor cells with sieve-like perforation, fused glands with irregular borders or back-to-back glands without intervening stroma. Patients were categorized into four groups according to the percentage of CGP component (0%, 1–19%, 20–49%, 50–100%). Cox’s proportional hazards model was applied to analyze recurrence free survival (RFS) and overall survival (OS). Results A total of 950 patients with resected lung adenocarcinoma was enrolled. The most frequent driver mutation in this cohort was EGFR and was detected in 624 (65.7%) patients. EGFR mutation was more frequently observed in patients with <20% CGP than in patients with ≥20% CGP (73.6% vs. 60.2%), while KRAS mutation and ALK rearrangement was significantly associated with ≥20% CGP. Patients with 20% or greater CGP exhibited significant worse RFS (P<0.001) and OS (P<0.001) than their counterparts. Moreover, the multivariate Cox regression analysis confirmed that CGP (≥20%) was a risk factor for a worse RFS (P=0.001) and OS (P<0.001) independent of staging and gene mutation. Smaller portion of CGP (<20%) were comparable in RFS and OS to those without CGP (0%). There was also no significant difference in RFS and OS between the 20–49% and ≥50% group. Conclusions Our study provided mutational profile of patients with different CGP, validated CGP as a negative prognostic factor and provided extra evidences for the optimal cut-off value of CGP percentage.