Miracle-dz/UniFAR-FTUs huggingface dataset:
Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV1 and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.
A Proteomic Investigation to Discover Candidate Proteins Involved in Novel Mechanisms of 5-Fluorouracil Resistance in Colorectal Cancer

One of the main obstacles to therapeutic success in colorectal cancer (CRC) is the development of acquired resistance to treatment with drugs such as 5-fluorouracil (5-FU). Whilst some resistance mechanisms are well known, it is clear from the stasis in therapy success rate that much is still unknown. Here, a proteomics approach is taken towards identification of candidate proteins using 5-FU-resistant sublines of human CRC cell lines generated in house. Using a multiplexed stable isotope labelling with amino acids in cell culture (SILAC) strategy, 5-FU-resistant and equivalently passaged sensitive cell lines were compared to parent cell lines by growing in Heavy medium with 2D liquid chromatography and Orbitrap Fusion™ Tribrid™ Mass Spectrometry analysis. Among 3003 commonly quantified proteins, six (CD44, APP, NAGLU, CORO7, AGR2, PLSCR1) were found up-regulated, and six (VPS45, RBMS2, RIOK1, RAP1GDS1, POLR3D, CD55) down-regulated. A total of 11 of the 12 proteins have a known association with drug resistance mechanisms or role in CRC oncogenesis. Validation through immunodetection techniques confirmed high expression of CD44 and CD63, two known drug resistance mediators with elevated proteomics expression results. The information revealed by the sensitivity of this method warrants it as an important tool for elaborating the complexity of acquired drug resistance in CRC.
Coexistence of Aedes aegypti and Aedes albopictus in Jinghong City, Yunnan Province: A Survey of Aedes aegypti Invasion

We conducted this study to confirm that Aedes aegypti has invaded and colonized in Xishuangbanna, Yunan province, China. And we conducted a larval survey for dengue mosquito vectors, Ae. aegypti and Ae. albopictus, to assess on possible competition for breeding sites between these both species in urban environment in Jinghong city. The study was carried out at least once a month in February and March, November and December, and three times for each month from April to October in 2014 in five communities in the municipality of Jinghong city. No less than 50 houses were surveyed each time in one place. We collected immature stages of mosquitoes from all types of breeding sites in houses and their premises. Morphological species identification was carried for Ae. aegypti and Ae. albopictus. Both species occurred in all surveyed areas. Aedes aegypti has occupied a considerable composition (67.75%) since the uncertain time of its first invasion to Jinghong city. Aedes aegypti was predominant species indoor (74.19%), but also presented in surrounding environment (25.81%); while Ae. albopictus favored the outdoor environment (54.55%) as well as in houses (45.45%). We gave the preference water containers (tires) for dengue vectors, described different distribution in different investigated places, and showed with monthly variance by indices of BI and CI. We gave our rational explanation for the variance with raining in this area, Aedes keep a high density value during the rainy season. For both dengue vectors, the possibility cannot be excluded that the invasion of Ae. aegypti in the city might lead to a decrease or elimination of Ae. albopictus in houses and dwellings. Furthermore, we also found that both dengue vectors have already occupied the breeding sites in houses and their premises with water container in Jinghong city, and both should be managed during dengue epidemic season. These findings from this study are relevant for dengue vector control programs
Clinical Characteristics and Quality of Life in a Cohort of Polish Pediatric Patients with Hereditary Angioedema

Hereditary angioedema (HAE) is a rare genetic disease. It is characterized by recurrent attacks of angioedema. Evidence to what extent it affects patient functioning is limited in the pediatric population. We aimed to determine the clinical characteristics and management of Polish children with HAE and to measure the health-related quality of life (HRQoL) of these patients. This cross-sectional study was conducted among 21 pediatric patients and their caregivers, as well as 21 respective controls randomly selected from the general population. During routine follow-up visits, standardized pediatric quality of life questionnaires (PedsQLTM 4.0) were administered to all caregivers and adolescents (≥13 years). Caregivers also completed a structured medical interview regarding the clinical characteristics and treatment of children with HAE during the previous six months. During this period, 57% of patients had low (group I), 24% moderate (group II), and 19% high (group III) HAE activity, corresponding to ≥10 attacks per 6 months. None of the patients received long-term prophylaxis. The children in group III had a lower HRQoL than other groups and controls on all dimensions of the PedsQLTM 4.0. The lowest scores in all groups were observed in the emotional functioning domain. Our data demonstrate that the burden of HAE on the quality of life of pediatric patients and their families encompasses a wide range of daily functioning.
Working conditions and attitudes towards work: the case of Portuguese youth from Braga

The purpose of this study is to explore the working conditions and attitudes towards work among the youth of Braga, Portugal. Focusing on residents of the Municipality of Braga born between 1990 and 2000, we employed a quantitative approach using a non-probabilistic convenience sampling method, with a sample size of 406 people. The survey, conducted through questionnaires, reveals a complex interplay between the youth’s work attitudes and their conditions. Despite the predominance of precarious employment, their work experiences and expectations do not entirely reflect this instability. Our findings suggest a shift in the role of work in the youths’ identity compared to previous generations. This shift, common in post-industrial societies, shows that their identity is increasingly tied to the sociability their work enables and other life spheres where they seek fulfilment, as evidenced by how they utilize their earnings from these occupations.
Datations par radiolaires (Carbonifere, Permien et Trias) en Thailande nord-occidentale. Mise en evidence de nappe de charriage et d' olistostromes

The classical Paleozoic stratigraphic column in NW Thailand was described as a single Ordovician to Permian marine succession (including undated radiolarites), considered to be tectonized in Triassic time. Ages obtained from radiolarite dating (Carboniferous to Triassic) demonstrate the existence of a separated sedimentary basin far from detritic sources and far from the deposition area of the Carboniferous to Triassic limestones. The present structural imbrication of radiolarites with limestones and detritic series is interpreted in terms of tectonic nappes with considerable shortening, and olistostrome deposits
The Impact of Demographic Characteristics on Parenting Stress among Parents of Children with Disabilities: A Cross-Sectional Study

Even though it is already known that parents of children with developmental delays or disabilities experience higher parenting stress than families of typically developing children, the contributing factors need to be analyzed in more detail. The aim of this cross-sectional study was to examine the influence of demographic characteristics on parenting stress from caring for a disabled child and to identify possible protective or additional stressful social factors. A total of 611 mothers and fathers of children with developmental delays, chronic diseases, or disabilities completed two questionnaires during their medical appointments at the Children’s Development Center (CDC) of Leipzig University Hospital between June 2020 and February 2021. These consisted of the German versions of the Parenting Stress Index (PSI) and the Impact on Family Scale (IOFS). To determine differences between the various groups, we used parametric and non-parametric tests. Mothers and single parents are significantly more strained than fathers and non-single parents. Parents with vocational training, those who graduated with a higher-level diploma, and those within employment report a higher financial burden. While unemployed and full-time workers experience the lowest stress, parents who work part-time or exclusively take care of their child show higher levels of stress. Looking at the age of the child, parents of children of young primary school age are the most stressed, and those of infants are the least stressed. These findings suggest that mothers and single parents especially should receive more support, and parents need to be provided with more attention during their child’s entry into school. Possible limitations and the influence of the COVID-19 pandemic are discussed.
Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis.
Pohjois-Karjalan metsäkeskuksen alueen metsävarat 1966–2000

Tässä julkaisussa esitetään valtakunnan metsien yhdeksänteen inventointiin (VMI9) perustuvat PohjoisKarjalan metsäkeskuksen alueen metsävaratiedot ja niiden muutokset 1966–2000 sekä analysoidaan muutosten syitä. Lisäksi artikkelissa kuvataan yleispiirteet otantamenetelmästä. Inventoinnin otantamenetelmää, maastomittauksia ja tuloslaskentaa kehitettiin yhdeksättä inventointia varten. Menetelmä on kuvattu EteläPohjanmaan tulosjulkaisun yhteydessä (Metsätieteen aikakauskirja 2B/1998). Pohjois-Karjalan metsäkeskuksen alue muuttui vuonna 1996, kun metsälautakunnat muutettiin metsäkeskuksiksi. Tähän julkaisuun laskettiin uudelleen nykyisen metsäkeskuksen alueen tulokset viidennestä inventoinnista eli vuodesta 1966 lähtien. Metsien käyttö on ollut voimakasta tarkastelujaksolla, mutta samalla metsien hoitoa on tehostettu. Puuvaranto on noussut vuoden 1966 inventoinnin 118 milj. m3:stä 157 milj. m3:iin. Puuston vuotuinen kasvu on samaan aikaan noussut 4,7 milj. m3:stä 7,2 milj. m3:iin. Kahdeksannen inventoinnin jälkeen kaikkien puulajien varanto ja kasvu ovat nousseet. Kuusen hakkuut ovat 1990-luvun lopulla ylittäneet kasvun, mutta sekä varanto että kasvu ovat nousseet VMI8:n ja VMI9:n välillä toisin kuin useilla muilla alueilla Etelä-Suomessa. Seuraavalla 10-vuotiskaudella voitaisiin hakkuita tehdä metsänhoidollisin perustein 936 000 ha:lla. Näistä ensiharvennuksia on 307 000 ha. Alle 60-vuotiaiden metsien ala on suurentunut, 61–80-vuotiaiden vähentynyt ja yli 80-vuotiaiden pysynyt likimain ennallaan VMI8:n ja VMI9:n välillä. Uudistuskypsiä ja varttuneita kasvatusmetsiä on vähemmän kuin tasaiset hakkuumahdollisuudet edellyttäisivät. Yli 100-vuotiaita kuusikoita on suhteessa hieman enemmän ja 41–60-vuotiaita vähemmän kuin vastaavan ikäluokan männiköitä. Metsälain tarkoittamia erityisen tärkeitä elinympäristöjä on VMI:n mukaan 0,66 % yhdistetystä metsä-, kituja joutomaan alasta. Kuollutta puuta on metsäja kitumaalla keskimäärin 4,5 m3/ha, mikä on suurin VMI9:ssa tähän mennessä mitatuista metsäkeskuksittaisista keskiarvoista. Alueen metsät täyttävät ne metsäsertifi oinnin kriteerit, joissa tietolähteenä on VMI, edellyttäen, että vuotuista taimikonhoidon alaa lisätään inventointia edeltäneen viiden vuoden keskimääräisestä alasta.
Flood mapping in the lower Mekong River Basin using daily MODIS observations

ABSTRACT In flat homogenous terrain such as in Cambodia and Vietnam, the monsoon season brings significant and consistent flooding between May and November. To monitor flooding in the Lower Mekong region, the near real-time NASA Flood Extent Product (NASA-FEP) was developed using seasonal normalized difference vegetation index (NDVI) differences from the 250 m resolution Moderate Resolution Imaging Spectroradiometer (MODIS) sensor compared to daily observations. The use of a percentage change interval classification relating to various stages of flooding reduces might be confusing to viewers or potential users, and therefore reducing the product usage. To increase the product usability through simplification, the classification intervals were compared with other commonly used change detection schemes to identify the change classification scheme that best delineates flooded areas. The percentage change method used in the NASA-FEP proved to be helpful in delineating flood boundaries compared to other change detection methods. The results of the accuracy assessments indicate that the −75% NDVI change interval can be reclassified to a descriptive ‘flood’ classification. A binary system was used to simplify the interpretation of the NASA-FEP by removing extraneous information from lower interval change classes.
Rapid Ice Nucleation by Acetone-Silver Iodide Generator Aerosols

A field test conducted on 10 January 1987 confirmed a postulate that rapid ice nucleation occurs on wet silver iodide aerosols at temperatures below -6 C. The postulate was developed from laboratory tests and is consistent with results from winter orographic cloud seeding programs which have used ground generators sited at mountain tops and along ridges, where they are located within supercooled water clouds during their operation.
Polydopamine Blending Increases Human Cell Proliferation in Gelatin–Xanthan Gum 3D-Printed Hydrogel

Background: Gelatin–xanthan gum (Gel–Xnt) hydrogel has been previously modified to improve its printability; now, to increase its ability for use as cell-laden 3D scaffolds (bioink), polydopamine (PDA), a biocompatible, antibacterial, adhesive, and antioxidant mussel-inspired biopolymer, has been added (1–3% v/v) to hydrogel. Methods: Control (CT) and PDA-blended hydrogels were used to print 1 cm2 grids. The hydrogels’ printability, moisture, swelling, hydrolysis, and porosity were tested after glutaraldehyde (GTA) crosslinking, while biocompatibility was tested using primary human-derived skin fibroblasts and spontaneously immortalized human keratinocytes (HaCaT). Keratinocyte or fibroblast suspension (100 µL, 2.5 × 105 cells) was combined with an uncrosslinked CT and PDA blended hydrogel to fabricate cylinders (0.5 cm high, 1 cm wide). These cylinders were then cross-linked and incubated for 1, 3, 7, 14, and 21 days. The presence of cells within various hydrogels was assessed using optical microscopy. Results and discussion: PDA blending did not modify the hydrogel printability or physiochemical characteristics, suggesting that PDA did not interfere with GTA crosslinking. On the other hand, PDA presence strongly accelerated and increased both fibroblast and keratinocyte growth inside. This effect seemed to be linked to the adhesive abilities of PDA, which improve cell adhesion and, in turn, proliferation. Conclusions: The simple PDA blending method described could help in obtaining a new bioink for the development of innovative 3D-printed wound dressings.
Transcription Factor IRF7 is Involved in Psoriasis Development and Response to Guselkumab Treatment

Purpose Guselkumab is a highly effective biologic agent for treating psoriasis. This study aimed to explore potential transcription factors involved in psoriasis pathogenesis and response to guselkumab treatment, aiming to provide new therapeutic strategies for psoriasis. Patients and Methods We analyzed gene expression and single-cell RNA-seq data from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) that upregulated in psoriasis and downregulated after guselkumab treatment were subjected to enrichment analyses. Single-cell regulatory network inference and clustering (SENIC) and regulon module analyses identified different regulon activities between the lesion and non-lesion skin of psoriasis. Cell-cell communication analysis revealed interactions among specific cell clusters. Transcription factor (TF) regulons were identified from the guselkumab-specific regulon network. Gene set enrichment analysis (GSEA) confirmed the IRF7 regulon in the validation cohort. Finally, the expression level of IRF7 was identified in plaque psoriasis before and after 12 weeks of guselkumab therapy by immunohistochemical experiment. Results 799 DEGs were downregulated after guselkumab treatment. Enrichment analyses highlighted the interleukin-17 (IL-17) pathway in this gene set. The M2 module exhibited the primary difference in regulon activity. Strong cell-cell interactions were observed between keratinocytes and immune cells. IRF7 regulon had significant roles in psoriasis and treatment response, as validated by GSEA analysis using the IL-17 signaling pathway as a reference. The immunohistochemical analysis unveiled substantial differences in the expression levels of IRF7 in psoriatic skin samples before and after 12 weeks of guselkumab treatment. Conclusion IRF7 may be the key player in psoriasis pathogenesis and the therapeutic process involving guselkumab. Targeting IRF7 might offer new therapeutic strategies for psoriasis.
Unmet Horizons: Assessing the Challenges in the Treatment of TP53-Mutated Acute Myeloid Leukemia

Acute myeloid leukemia (AML) remains a challenging hematologic malignancy. The presence of TP53 mutations in AML poses a therapeutic challenge, considering that standard treatments face significant setbacks in achieving meaningful responses. There is a pressing need for the development of innovative treatment modalities to overcome resistance to conventional treatments attributable to the unique biology of TP53-mutated (TP53mut) AML. This review underscores the role of TP53 mutations in AML, examines the current landscape of treatment options, and highlights novel therapeutic approaches, including targeted therapies, combination regimens, and emerging immunotherapies, as well as agents being explored in preclinical studies according to their potential to address the unique hurdles posed by TP53mut AML.
Involvement of Palliative Care in Malignant Pleural Mesothelioma Patients and Associations with Survival and End-of-Life Outcomes

Malignant pleural mesothelioma is a rare, aggressive, and incurable cancer with a poor prognosis and high symptom burden. For these patients, little is known about the impact of palliative care consultation on outcomes such as mortality, hospital admissions, or emergency department visits. The aim of this study is to determine if referral to supportive and palliative care in patients with malignant pleural mesothelioma is associated with survival and decreased hospital admissions and emergency department visits. This is a retrospective chart review. Study participants include all malignant pleural mesothelioma patients seen at The Ottawa Hospital—an acute care tertiary center—between January 2002 and March 2019. In total, 223 patients were included in the study. The mean age at diagnosis was 72.4 years and 82.5% were male. Of the patients diagnosed between 2002 and 2010, only 11 (9.6%) were referred to palliative care. By comparison, of those diagnosed between 2011 and 2019, 49 (45.4%) were referred to palliative care. Median time from diagnosis to referral was 4.1 months. There was no significant difference in the median survival of patients referred for palliative care compared to those who did not receive palliative care (p = 0.46). We found no association between receiving palliative care and the mean number of hospital admissions (1.04 vs. 0.91) from diagnosis to death, and an increase in mean number of emergency department visits in the palliative care group (2.30 vs. 1.18). Although there was increased utilization of palliative care services, more than half of the MPM patients did not receive palliative care despite their limited survival. There was an increase in emergency department visits in the palliative care group; this may represent an increase in the symptom burden (i.e., indication bias) in those referred to palliative care.