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Ushbu tezisda mahalliy uzum navlaridan olinadigan mayizning sifat  ko‘rsatkichlari, oziq-ovqat xavfsizligi mezonlari va saqlash jarayoniga ta’sir qiluvchi  omillar kompleks yonda…

Ushbu tezisda mahalliy uzum navlaridan olinadigan mayizning sifat  ko‘rsatkichlari, oziq-ovqat xavfsizligi mezonlari va saqlash jarayoniga ta’sir qiluvchi  omillar kompleks yondashuv asosida tahlil qilindi. Mayiz sifatini baholashda  organoleptik xususiyatlar, namlik, suv faolligi, shakar va organik kislotalar miqdori,  rangning barqarorligi, mikrobiologik holat hamda mikotoksinlar xavfi asosiy mezonlar  sifatida ko‘rib chiqildi. Adabiyotlar tahlili pastroq harorat, barqaror nisbiy namlik,  namlik va kislorod o‘tkazuvchanligi cheklangan qadoqlash mayizning rang, tekstura  va mikrobiologik barqarorligini saqlashda muhimligini ko‘rsatadi. Shuningdek,  xomashyo navi, quritish usuli va dastlabki ishlov saqlashdagi sifat yo‘qotishlariga  bevosita ta’sir etishi asoslandi. 

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who ini…

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24–49%), GI-ORR was 37% (95% CI: 25–51%); 29% (95% CI: 11–49%) of responders lost response within 30 days, and 52% (95% CI: 29–72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54–128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade = 2 infectious events occurred in 51% of patients; Grade 3–4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms. © The Author(s), under exclusive licence to Springer Nature Limited 2026.

Background-Although great advances have been made in the prevention of hemolytic disease of the fetus and newborn, especially for anti-D, irregular antibodies still appear. In order to ascertain the s…

Background-Although great advances have been made in the prevention of hemolytic disease of the fetus and newborn, especially for anti-D, irregular antibodies still appear. In order to ascertain the situation in Spain, we conducted a survey among hospitals treating pregnant women. Materials and methods-We sent a survey to Spanish public hospitals comprising demographical data (ethnicity, number of pregnancies, type of fertilization), characteristics of antibodies (specificity, number, antigenic compatibility), cause of alloimmunization and the clinical consequences (fetal death, icterus, anemia) between 2016 and 2021. We characterized the risk posed by antibodies and their clinical impact according to previously described criteria. Results-During the study period, 574,140 children were born in the responding hospitals. Antibodies were detected in 1,055 women with 1,112 pregnancies, resulting in a 0.19% alloimmunization prevalence. The most common antibodies were anti-D (No.=393, 28.7%), anti-c (No.=204, 14.9%), anti-E (No.=199, 14.6%), anti-M (No.=129, 9.4%), and anti-Kell (No.=114, 8.3%). Incorrect prophylaxis administration in the current or past pregnancy accounted for 88.6% of anti-D, and 12 (6.5%) arose from an RhD-positive transfusion. When analyzing incompatible pregnancies (No.=424; 38%), 103 (24.3%) presented severe or very severe hemolytic disease, most of which (No.=92, 89%) were produced by high-risk antibodies, while only 11 cases were caused by medium-risk antibodies. Discussion-The prevalence of irregular antibodies during pregnancy in Spain is lower than previously described for other Western countries. The most important antibodies are anti-D, anti-c and anti-K. More efforts to characterize antibodies should be made in order to reduce their prevalence and clinical impact. ©SIMTIPRO S. © SIMTIPRO Srl.

Background Gliomas are the most common primary brain tumors in adults and encompass a spectrum from IDH-mutant gliomas to highly aggressive IDH-wild type glioblastomas (GBM). Despite advances in our u…

Background Gliomas are the most common primary brain tumors in adults and encompass a spectrum from IDH-mutant gliomas to highly aggressive IDH-wild type glioblastomas (GBM). Despite advances in our understanding of glioma biology, GBM remains largely incurable, with a median overall survival (mOS) of approximately 15 months and minimal improvements over recent decades. The current standard of care, maximal surgical resection followed by radiotherapy and temozolomide (TMZ) chemotherapy, has proven insufficient, and experimental approaches such as immune checkpoint inhibitors and CAR-T cell therapies have also failed to provide meaningful survival benefits. These limitations highlight the urgent need for innovative, patient-specific platforms to evaluate novel therapeutic strategies. Methods In this study, we established patient-derived glioma organoids (GOs) from 61 patients, including both IDH-mutant gliomas (GOmut) and IDH-wild type glioblastoma (GOwt). These organoids were characterized by a variety of techniques against their parental tumors. Afterwards, we performed in silico drug discovery with paired RNA-seq data and validated the results with diverse glioma models. Results GOs recapitulated the cellular heterogeneity, histological architecture, and molecular signatures of their parental tumors, including the preservation of clinically relevant features such as immune profiles, vascular structures, and tumor subtype. Notably, GOmuts retained the IDH mutation over extended culture periods. Importantly, GOs maintained resistance to standard chemotherapeutic agents, mirroring the limited response of gliomas to conventional chemotherapy. Our unbiased in silico screening via the DiSCoVER platform applied to RNA-seq data from paired tumors and GOs identified alectinib, dabrafenib, and ruxolitinib as promising candidates. All three compounds proved effective in in vitro cytotoxicity assays, with alectinib and ruxolitinib displaying significant antitumoral effects in vitro. Conclusions Our findings establish GOs as a clinically relevant and biologically faithful platform for therapeutic screening in glioma. By integrating transcriptomics-based drug discovery with a patient-specific organoid model, we present an easy to implement platform for more effective and personalized treatments for glioma patients. Our findings also support the inclusion of two compounds, alectinib and ruxolitinib, in future clinical investigations.

Historical questionnaire/s  1924/1948 and index cards, partly selected enclosures regarding the history of a German pharmacy, catalogued via Kalliope portal (Historischer Fragebogen 1924/1948 und…

Historical questionnaire/s  1924/1948 and index cards, partly selected enclosures regarding the history of a German pharmacy, catalogued via Kalliope portal (Historischer Fragebogen 1924/1948 und Karteikarten, ggf. gemeinfreie Anlagen zur Apothekengeschichte; als Katalog dient das Nachlassportal Kalliope): https://kalliope-verbund.info/DE-611-BF-70963 [Funktion: Im Findbuch anzeigen] Please note: The Kalliope catalogue entry might indicate related material in the archival folder which cannot be published due to copyright or other legal restrictions (NB: Das Katalogisat bei Kalliope kann auch auf Materialien - teils erheblichen Umfangs - verweisen, die aus archiv- oder urheberrechtlichen Gründen nicht veröffentlicht werden dürfen).

INTRODUCTION AND OBJECTIVES: The study examines how hypoxaemia in obstructive sleep apnoea (OSA) relates to cancer. It focuses on CD25, an immune-checkpoint, analyzing its levels in OSA patients with …

INTRODUCTION AND OBJECTIVES: The study examines how hypoxaemia in obstructive sleep apnoea (OSA) relates to cancer. It focuses on CD25, an immune-checkpoint, analyzing its levels in OSA patients with and without cancer to assess whether CD25 could serve as a biomarker for cancer mortality. MATERIALS AND METHODS: We investigated the plasma levels of soluble CD25 (sCD25) in three independent cohorts: patients with no evidence of cancer, with melanoma, and with lung cancer. We explored the role of hypoxaemia by intermittent hypoxia (IH) and HIF-1a inhibition in vitro models. RESULTS: Our results suggest that sCD25 increases with hypoxemia severity in OSA, both with or without cancer. OSA patients also exhibit early upregulation of membrane-bound CD25 in T lymphocytes. Our findings corroborate that IH, via HIF-1a, mediates the upregulation of both membrane-bound and sCD25. sCD25 levels correlate with markers of melanoma and lung cancer aggressiveness, and elevated sCD25 levels are associated with higher lung cancer mortality risk. CONCLUSION: Our study indicates that hypoxia mediates the increase of CD25 in OSA patients. In turn, our data revealed sCD25 were related to tumour aggressiveness in OSA patients with melanoma or lung cancer, and suggest sCD25 as a potential novel biomarker to stratify OSA patients with lung cancer by mortality risk.

INTRODUCTION: Accurate assessment of disease activity in SLE is crucial but challenging due to its varied clinical manifestations and severity. Current tools like the SLE Disease Activity Index (SLEDA…

INTRODUCTION: Accurate assessment of disease activity in SLE is crucial but challenging due to its varied clinical manifestations and severity. Current tools like the SLE Disease Activity Index (SLEDAI) have limitations, including unvalidated cut-off points, low sensitivity to certain severe features and an overemphasis on serological markers. There is a need for improved definitions of disease activity. METHODS: We analysed data from 1463 patients with SLE in the prospective, multicentre RELESSER-PROS cohort (39 Spanish hospitals) over five annual visits. A panel of lupus experts used the Delphi method to develop new definitions for moderate disease activity state (MODAS) and severe disease activity state (SEDAS). These incorporated clinical SLEDAI (cSLEDAI), selected severe non-SLEDAI manifestations (eg, neuropsychiatric involvement, proteinuria, severe haematological features) and the Physician Global Assessment. We compared the predictive performance of MODAS/SEDAS with SLEDAI for mortality, organ damage, severe flares, hospitalisations and health-related quality of life, using receiver operating characteristics curves. RESULTS: At baseline, 20% of patients met MODAS criteria and 24.6% SEDAS criteria, versus 10.5% and 3.0%, respectively, by SLEDAI. MODAS/SEDAS reclassified 19.9% of patients considered mild by SLEDAI, and 53.3% of moderate cases. MODAS/SEDAS showed modest but consistent improvement in predictive accuracy for damage (area under the curve 0.570 vs 0.550), flares (0.609 vs 0.564) and hospitalisations (0.609 vs 0.565). These definitions were associated with worse outcomes and demonstrated a dose-response relationship, although the overall predictive ability remained moderate. CONCLUSION: MODAS and SEDAS offer an alternative framework for defining moderate and severe SLE activity, with modest but consistent improvements in predictive performance compared with SLEDAI. By integrating cSLEDAI, key severe features and physician judgement, they improve prognostic performance and support a severity-based approach to clinical management and research. Their clinical utility remains preliminary, and further external validation is required before routine implementation. © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

Pompe disease or glycogenosis type II is a rare disease caused by mutations in the GAA gene that leads to deficiency of the acid alpha-1,4-glucosidase enzyme. As a result of the enzymatic defect, a pr…

Pompe disease or glycogenosis type II is a rare disease caused by mutations in the GAA gene that leads to deficiency of the acid alpha-1,4-glucosidase enzyme. As a result of the enzymatic defect, a progressive accumulation of intralysosomal glycogen occurs in various tissues, causing smooth, cardiac and skeletal muscle involvement. When the age of onset of the disease is after the first year of life, it is called late-onset Pompe disease (LOPD). Weakness of the axial and proximal waist muscles and respiratory dysfunction are common manifestations. Enzyme replacement therapy (ERT) has been available for more than 15 years and is the standard treatment. This therapy changes the course of the disease, although the effectiveness of the treatment reduces over time. New enzyme therapies represent new treatment opportunities for patients with LOPD. Here we present updated recommendations from a group of experts in Pompe disease on the diagnosis, treatment and follow-up of LOPD patients, with the aim of providing a guide for the clinical management of the disease. Copyright © 2025 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

What's Changed fix: Keep requested keys alive in the naive scheduler by @SimonHeybrock in https://github.com/scipp/sciline/pull/240 Full Changelog: https://github.com/scipp/sciline/compare/26.8.0...…

What's Changed fix: Keep requested keys alive in the naive scheduler by @SimonHeybrock in https://github.com/scipp/sciline/pull/240 Full Changelog: https://github.com/scipp/sciline/compare/26.8.0...26.9.0

To evaluate the effectiveness and tolerability of dolutegravir/lamivudine (DTG/3TC) at 96 weeks in virologically suppressed persons with HIV, both overall and across subgroups, within CoRIS, a large m…

To evaluate the effectiveness and tolerability of dolutegravir/lamivudine (DTG/3TC) at 96 weeks in virologically suppressed persons with HIV, both overall and across subgroups, within CoRIS, a large multicenter cohort in Spain, in 2018-2023 METHODS: We included treatment-experienced adults with HIV who were virologically suppressed (viral load <50 copies/mL) when switching to DTG/3TC. We calculated the proportion maintaining viral suppression (VS), change in CD4 cell counts, virological failure (VF; two consecutive viral load (VL) =50 copies/mL or one =1000 copies/mL), and discontinuations due to adverse events (AEs) up to 96 weeks post-switch. Outcomes were stratified by sex, age, region of origin, antiretroviral regimen at switch, and previous VF RESULTS: Among 2058 participants (22.5% women), 95.9% maintained VS, 2.2% experienced VF, and 2.2% discontinued due to AEs. In multivariable analysis, no significant differences in VS, VF or CD4 change were observed across most subgroups. Participants aged =50 years were more likely to maintain VS, had lower VF risk, and a smaller CD4 increase compared with <50 years. Prior VF was associated with lower likelihood of maintaining VS and higher VF risk. Switching from 2NRTIs + PI or 2NRTIs + INSTI increased risk of VF compared with NRTIs+NNRTI CONCLUSIONS: DTG/3TC showed high effectiveness and tolerability at 96 weeks, with consistent outcomes across most subgroups. Previous VF reduced the likelihood of sustained VS. © 2025 British HIV Association.