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Resumo A visão baseada em capacidades é central ao entendimento de como ecossistemas podem ser gerenciados. No entanto, apesar da relevância deste tema, ainda existe uma lacuna na literatura sobre as capacidades necessárias à gestão de ecossistemas. O objetivo desse artigo é identificar e mapear as capacidades aplicadas à gestão de ecossistemas de negócios. A metodologia consistiu em uma revisão sistemática da literatura considerando duas bases de dados: Web of Science e Scopus. No total, foram analisados 789 trabalhos; destes 89 fizeram a ponte entre capacidades e ecossistemas. A análise de conteúdo foi realizada por meio de codificação, resultando em um agrupamento de 11 capacidades - uma foi dinâmica e as outras dez foram operacionais. Os resultados obtidos incluem identificação, mapeamento e estruturação das capacidades dinâmicas e operacionais para a gestão do ecossistema, bem como para sua dispersão entre seus atores: firma focal, fornecedores e complementadores. Desenvolvemos um framework de gestão das capacidades do ecossistema, o qual apresenta a capacidade dinâmica como elo central e impulsionador do conjunto das capacidades do ecossistema, que incluem as capacidades para: o seu alinhamento, a sua sustentação, o seu crescimento e sustentação das empresas nele. Contribuímos com a literatura e prática gerencial ao apresentar uma estruturação de capacidades para gestão do ecossistema, agrupadas em um framework que mostra as implicações da presença das diferentes capacidades no ecossistema. Também contribuímos ao apresentar sugestões de pesquisas futuras para cada agrupamento de capacidades.

O presente artigo verifica as contribuições das incubadoras empresariais na gestão e criação do conhecimento em favor das empresas incubadas. Tem por objetivo compreender as contribuições citadas e analisar a influência do processo de incubação a partir do mapeamento de informações gerais sobre as instituições participantes deste estudo, assim como mecanismos, ferramentas e estruturas para a gestão e criação do conhecimento as quais podem alavancar o desenvolvimento sustentável de empresas que estão em estágio de estruturação. Apresenta pesquisa ancorada na revisão de literatura sobre incubadoras empresariais e gestão do conhecimento. Durante o processo de investigação, para avaliar e mapear os objetivos estabelecidos, a entrevista e, por conseguinte, o roteiro de entrevista foram utilizados como método e instrumento de coleta de dados, dentro de uma abordagem qualitativa. A partir disso, 3 empresas, dentre elas, um hub de conexões e duas incubadoras empresariais foram entrevistadas e suas respostas sistematizadas no estudo de caso múltiplo em questão. Sendo assim, a pesquisa realizada revelou que o processo de incubação proporciona e contribui de forma intensa com a criação e gestão do conhecimento às organizações incubadas ao desenvolver um ecossistema de inovação e fornecer mecanismos, estruturas e ferramentas que possibilitam o gerenciamento e desenvolvimento de novos conhecimentos nas organizações nascentes, além de vantagens competitivas.

Alteration of metabolism in cancer cells is a central aspect of the mechanisms that sustain aggressive traits. Aldo–keto reductase 1 B1 (AKR1B1) catalyzes the reduction of several aldehydes to alcohols consuming NADPH. Nevertheless, the ability of AKR1B1 to reduce different substrates renders difficult to comprehensively ascertain its biological role. Recent evidence has implicated AKR1B1 in cancer; however, the mechanisms underlying its pro-oncogenic function remain largely unknown. In this work, we report that AKR1B1 expression is controlled by the p53 tumor suppressor. We found that breast cancer patients bearing wild-type TP53 have reduced AKR1B1 expression. In cancer cell lines, p53 reduced AKR1B1 mRNA and protein levels and repressed promoter activity in luciferase assays. Furthermore, chromatin immunoprecipitation assays indicated that p53 is recruited to the AKR1B1 promoter. We also observed that AKR1B1 overexpression promoted metastasis in the 4T1 orthotopic model of triple-negative breast cancer. Proteomic analysis of 4T1 cells overexpressing AKR1B1 showed that AKR1B1 exerts a marked effect on proteins related to metabolism, with a particular impact on mitochondrial function. This work provides novel insights on the link between the p53 pathway and metabolism in cancer cells and contributes to characterizing the alterations associated to the pathologic role of AKR1B1.

الأهداف: تهدف هذه الدراسة إلى بيان كيفية توظيف الحديث الشريف وطريقة الاستدلال به، واستنباط الاختيارات والآراء الفقهية من خلاله، والوقوف على فهمه والمراد منه، عند مدرستي الشام والكوفة، عند الإمامين الأوزاعي وأبي حنيفة. المنهجية: من خلال الإمامين الأوزاعي وأبي حنيفة واللذين يعدَان من أبرز من يمثل تلك المدرستين. تم دراسة مسائل فقهية لأبواب مختلفة من صحيح البخاري، وتتبع أقوال الإمامين في تلك المسائل، وكيفية توظيفهما الحديث في استنباط الحكم الشرعي، وبيان وجه الدلالة منه. النتائج: توصلت الدراسة إلى نتائج أكدت على أهمية الحديث النبوي وأثره في استنباط الاختيارات والآراء الفقهية للإمامين الأوزاعي وأبي حنيفة، معتمدين على ذلك بأصولهما المذهبية الفقهية، ومناهجهما في الاستنباط، والتي أساسها القرآن والسنة والإجماع والقياس. الخلاصة: مدرستا الشام والكوفة من المدارس الحديثية التي بنت اختياراتها وأحكامها على الحديث الشريف استدلالا، واستنباطا. وتوصي الدراسة إلى ضرورة الاطلاع على مسالك فقهية أخرى لأئمة مذاهب في مدارس أخرى، والوقوف على مناهجهم في كيفية الاستدلال بالحديث الشريف، بالإضافة إلى بيان تكوينهم الفقهي من خلاله.

الأهداف: تهدف هذه الدراسة إلى بيان موافقة الولي في عقد الزواج بين قانون الأحوال الشخصية الأردني لعام 2019 والمستمد من الشريعة الإسلامية، واتفاقية سيداو (اتفاقية القضاء على كافة أشكال التمييز ضد المرأة). المنهجية: اعتمدت الدراسة على المنهج الإستقرائي والتحليلي من خلال استقراء مصادر النصوص الشرعية وتحليلها في ظل أحكام الشريعة الإسلامية، وكذلك العمل مع نصوص القوانين (قانون الأحوال الشخصية الأردني واتفاقية سيداو) في موضوع البحث. النتائج: توصلت الدراسة إلى إنّ موافقة الولي في عقد الزواج في قانون الأحوال الشخصية الأردني 2019 شرط لصحته، بخلاف اتفاقية سيداو التي لا تعتبر وجوده في العقد. الخلاصة: خلصت الدراسة إلى أنّ مسألة موافقة الولي في عقد الزواج من المسائل التي أثارت الجدل الواسع في الآونة الأخيرة، خاصة بعد انتشار القوانين والاتفاقيات التي تبيح للمرأة الزواج دون موافقة الولي، وهذا لا يتناسب مع أحكام الشريعة الإسلامية. لذا توصي الدراسة بضرورة الحديث عن مخاطر الاتفاقية فيما يتعلق بعقد الزواج، وعدم السماح لها بالتأثير على قانون الأحوال الشخصية الأردني

Objective: To compare the effectiveness and cost of in‐vitro fertilization (IVF) with or without preimplantation genetic testing for aneuploidy (PGT‐A) when only one or two blastocysts are obtained. Methods: A dataset was gathered from 1829 patients including 368 non‐PGT‐A and 1461 PGT‐A cycles with one or two blastocysts obtained, between April 2013 and July 2022. Patients were matched 1:1 by propensity‐score matching for maternal age, number of metaphase‐II oocytes inseminated and number of blastocysts obtained, achieving a database of 242 patients per group. The non‐PGT‐A and PGT‐A groups were compared for differences in live birth rate (LBR) per embryo transfer (ET), cumulative LBR per patient, miscarriage rate (MR) per clinical pregnancy, number of days between oocyte retrieval and conclusion of the IVF cycle (primary outcome), mean expenses incurred at the clinic and incremental cost‐effectiveness ratio (ICER). Results: More than twice as many ETs were conducted in the non‐PGT‐A group compared with the PGT‐A group, yet the cumulative LBR per patient was similar between groups (23.6% (95% CI, 18.5–29.5%) vs 27.3% (95% CI, 21.9–33.4%)). This outcome was achieved with a higher LBR per ET (16.2% (95% CI, 12.6–20.5%) vs 41.5% (95% CI, 33.9–49.4%)) and lower MR per clinical pregnancy (30.1% (95% CI, 21.8–42.6%) vs 13.9% (95% CI, 7.5–24.0%)) in the PGT‐A group. The MR per patient was also lower in the PGT‐A group (9.5% (95% CI, 6.2–14.1%) vs 4.5% (95% CI, 2.4–8.2%)). The mean duration between oocyte retrieval and IVF cycle conclusion was 131 (95% CI, 113–150) days in the non‐PGT‐A group vs 74 (95% CI, 61–87) days in the PGT‐A group (P < 0.001; power = 99.8%). The ICER of PGT‐A for the months saved between oocyte retrieval and conclusion of the IVF cycle was €499 overall, ranging between €170 and €2065 according to the number of blastocysts obtained and/or maternal age. The ICER of PGT‐A for prevented miscarriages was €18 968, decreasing to €3525 when calculated among patients aged ≥ 35 years with two blastocysts obtained. Conclusions: When conducted in expert IVF clinics for patients indicated for the procedure, PGT‐A is clinically valuable even when only one or two blastocysts are obtained. PGT‐A reduces the number of ETs and miscarriages while the cumulative LBR per patient remains unaffected, and allows these outcomes to be achieved in a shorter timeframe. The ICER of PGT‐A vs non PGT‐A decreased as maternal age increased. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can more reliable time cut-offs of embryo developmental incompetence be generated by combining time-lapse technology (TLT), artificial intelligence, and preimplantation genetics screening for aneuploidy (PGT-A)? SUMMARY ANSWER Embryo developmental incompetence can be better predicted by time cut-offs at multiple developmental stages and for different ranges of maternal age. WHAT IS KNOWN ALREADY TLT is instrumental for the continual and undisturbed observation of embryo development. It has produced morphokinetic algorithms aimed at selecting embryos able to generate a viable pregnancy, however, such efforts have had limited success. Regardless, the potential of this technology for improving multiple aspects of the IVF process remains considerable. Specifically, TLT could be harnessed to discriminate developmentally incompetent embryos: i.e. those unable to develop to the blastocyst stage or affected by full-chromosome meiotic aneuploidies. If proven valuable, this application would prevent the non-productive use of such embryos, thereby improving laboratory and clinical efficiency and reducing patient stress and costs due to unnecessary embryo transfer and cryopreservation. STUDY DESIGN, SIZE, DURATION The training dataset involved embryos of PGT-A cycles cultured in Embryoscope with a single media (836 euploid and 1179 aneuploid blastocysts and 1874 arrested embryos; 2013–2020). Selection criteria were ejaculated sperm, own (not donated) fresh oocytes, trophectoderm biopsy and comprehensive-chromosome-testing to diagnose uniform aneuploidies. Out-of-sample (30% of training), internal (299 euploid and 490 aneuploid blastocysts and 680 arrested embryos; 2021–2022) and external (97 euploid, 110 aneuploid and 603 untested blastocysts and 514 arrested embryos, 2018 to early 2022) validations were conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS A training dataset (70%) was used to define thresholds. Several models were generated by fitting outcomes to each timing (tPNa-t8) and maternal age. ROC curves pinpointed in-sample classification values associated with 95%, 99% and 99.99% true-positive rate for predicting incompetence. These values were integrated with upper limits of maternal age ranges (<35, 35-37, 38–40, 41–42, and >42 years) in logit functions to identify time cut-offs, whose accuracy was tested on the validation datasets through confusion matrices. MAIN RESULTS AND THE ROLE OF CHANCE For developmental (in)competence, the best performing (i) tPNa cut-offs were 27.8 hpi (error-rate: 0/743), 32.6 hpi (error rate: 0/934), 26.8 hpi (error rate: 0/1178), 22.9 hpi (error-rate: 1/654, 0.1%) and 17.2 hpi (error rate: 4/423, 0.9%) in the <35, 35–37, 38–40, 41–42, and >42 years groups, respectively; (ii) tPNf cut-offs were 36.7 hpi (error rate: 0/738), 47.9 hpi (error rate: 0/921), 45.6 hpi (error rate: 1/1156, 0.1%), 44.1 hpi (error rate: 0/647) and 41.8 hpi (error rate: 0/417); (iii) t2 cut-offs were 50.9 hpi (error rate: 0/724), 49 hpi (error rate: 0/915), 47.1 hpi (error rate: 0/1146), 45.8 hpi (error rate: 0/636) and 43.9 hpi (error rate: 0/416); (iv) t4 cut-offs were 66.9 hpi (error rate: 0/683), 80.7 hpi (error rate: 0/836), 77.1 hpi (error rate: 0/1063), 74.7 hpi (error rate: 0/590) and 71.2 hpi (error rate: 0/389); and (v) t8 cut-offs were 118.1 hpi (error rate: 0/619), 110.6 hpi (error rate: 0/772), 140 hpi (error rate: 0/969), 135 hpi (error rate: 0/533) and 127.5 hpi (error rate: 0/355). tPNf and t2 showed a significant association with chromosomal (in)competence, also when adjusted for maternal age. Nevertheless, the relevant cut-offs were found to perform less well and were redundant compared with the blastocyst development cut-offs. LIMITATIONS, REASONS FOR CAUTION Study limits are its retrospective design and the datasets being unbalanced towards advanced maternal age cases. The potential effects of abnormal cleavage patterns were not assessed. Larger sample sizes and external validations in other clinical settings are warranted. WIDER IMPLICATIONS OF THE FINDINGS If confirmed by independent studies, this approach could significantly improve the efficiency of ART, by reducing the workload and patient impacts (extended culture and cleavage stage cryopreservation or transfer) associated with embryos that ultimately are developmentally incompetent and should not be considered for treatment. Pending validation, these data might be applied also in static embryo observation settings. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the participating institutions. The authors have no conflicts of interest to declare TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Upon progesterone stimulation, Endometrial Stromal Cells (EnSCs) undergo a differentiation program into secretory cells (decidualization) to release in abundance factors crucial for embryo implantation. We previously demonstrated that decidualization requires massive reshaping of the secretory pathway and, in particular, of the Golgi complex. To decipher the underlying mechanisms, we performed a time-course transcriptomic analysis of in vitro decidualizing EnSC. Pathway analysis shows that Gene Ontology terms associated with vesicular trafficking and early secretory pathway compartments are the most represented among those enriched for upregulated genes. Among these, we identified a cluster of co-regulated genes that share CREB3L1 and CREB3L2 binding elements in their promoter regions. Indeed, both CREB3L1 and CREB3L2 transcription factors are up-regulated during decidualization. Simultaneous downregulation of CREB3L1 and CREB3L2 impairs Golgi enlargement, and causes dramatic changes in decidualizing EnSC, including Golgi fragmentation, collagen accumulation in dilated Endoplasmic Reticulum cisternae, and overall decreased protein secretion. Thus, both CREB3L1 and CREB3L2 are required for Golgi reshaping and efficient protein secretion, and, as such, for successful decidualization.