bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normativas em reprodução assistida e conhecimento das pacientes
Authors: Castro Julia Maria de , Resende Cecília Maria de Maia , Oppenheimer Drauzio 
Published: October 2023

A infertilidade é considerada pela Organização Mundial de Saúde (OMS) como um problema de saúde pública global, afetando em torno de 15% da população mundial. No Brasil não há legislação específica quanto ao tratamento da infertilidade e a utilização das técnicas de reprodução assistida. O Conselho Federal de Medicina (CFM) é quem, através das normativas éticas, dita as regras seguidas pela classe médica; e a última Resolução é de n° 2.320/2022. O presente estudo tem como objetivo averiguar o grau de conhecimento por conta dos pacientes destas normativas do CFM. Foi realizado um estudo observacional transversal multicêntrico na Faculdade de Medicina de Itajubá (MG) e LabFiv - Clínica Gera (SP). A pesquisa foi realizada por meio de levantamento bibliográfico e aplicação de questionário online (Google Forms) aos casais que procuraram a Clínica de Fertilidade e Reprodução Humana Gera (SP). Nossos achados revelaram uma prevalência de 66% das pacientes que possuem conhecimento a respeito da Resolução do Conselho Federal de Medicina; 64% têm conhecimento da quantidade de embriões dispostos em uma palheta; 56% estão informadas a respeito da possibilidade de biópsia embrionária; 74% estão cientes do que fazer com os embriões excedentes; 80% estão conscientes do termo específico oferecido pelo laboratório após decisão de descarte. Dessa forma, conclui-se que maioria das pacientes tem conhecimento sobre as normativas do CFM relacionadas à fertilização in vitro (FIV) e à criopreservação de embriões.
Via aérea pediátrica: Conceitos e gestão
Authors: Almeida Manoel Guedes de , Barbosa Débora Regina Marques 
Published: October 2023

Um dos aspectos de maior relevância na anestesiologia pediátrica é o manejo da via aérea (VA). As diferenças anatômicas desta população fazem com que seja mais suscetível a efeitos adversos de dispositivos projetados para seu manejo. Muitas das descrições anatômicas atuais são baseadas em descobertas de mais de meio século de descrições em cadáveres. Desde há quase uma década há estudos de imagens de VA em crianças que identificam a glote como a porção mais estreita, e a laringe mais cilíndrica que cônica. Esses efeitos colaterais têm impacto nos dispositivos de manejo de VA escolhidos.
Riscos da automedicação: Avaliação da prática entre acadêmicos de um centro universitário no município de Pindamonhangaba-SP
Authors: Paes José Francisco Brum , Freitas Dailton de , Brum Helineide Cristina Campos 
Published: October 2023

A automedicação é o ato de administração de medicamentos sem possuir o conhecimento técnico ou habilitação para tal fim e sem que o mesmo tenha sido prescrito por um profissional da área da saúde. Esse é um ato que pode gerar muitos prejuízos à saúde do indivíduo que o pratica principalmente quando este não possui os conhecimentos técnicos. Diante desse contexto foi realizado um estudo qualitativo e exploratório, com estudantes universitários através da aplicação de um questionário semiestruturado. O objetivo deste estudo foi avaliar as práticas de automedicação executadas por estudantes de cursos da área da saúde um centro universitário na cidade de Pindamonhangaba-SP, além de apresentar os riscos e malefícios do ato de automedicar-se. Verificou-se que 100% dos alunos voluntários sabiam o que era a prática da automedicação e que 85% possuíam conhecimento sobre os riscos de tal prática. Observou-se que 98% do grupo de estudo realizava a prática da automedicação influenciados pelo fato de possuírem a medicação em casa. Observou-se também que 44,3% dos participantes do estudo buscaram as informações sobre os medicamentos por meio da pesquisa na internet. Conclui-se que a automedicação é uma prática muito comum entre os estudantes da área da saúde, o que gera uma preocupação, pois apesar de conhecerem os riscos associados à prática, ainda assim a realizaram.
Integrated treatment guided by RNA-seq–based endometrial receptivity assessment for infertility complicated by MEN1
Authors: Huang Xi , Fu Jing , Zhang Qiong , Zhao Jing , Yao Zhongyuan , Xia Qiuping , Tang Hongying , Xu Aizhuang , He Aihua , Liang Shaolin , Lu Sijia , Li Yanping 
Published: October 2023

BackgroundPreimplantation genetic testing (PGT) serves as a tool to avoid genetic disorders in patients with known genetic conditions. However, once a selected embryo is transferred, implantation success is attained independent of embryo quality. Using PGT alone is unable to tackle implantation failure caused by endometrial receptivity (ER) abnormalities in these patients.MethodsWe validated our newly developed RNA-seq–based ER test (rsERT) in a retrospective cohort study including 511 PGT cycles and reported experience in treating an infertile female patient complicated by multiple endocrine neoplasia type 1 (MEN1).ResultsSignificant improvement in the clinical pregnancy rate was found in the performed personalized embryo transfer (pET) group (CR, 69.7%; P = 0.035). In the rare MEN1 case, pET was done according to the prediction of the optimal time of window of implantation after unaffected blastocysts were obtained by PGT-M, which ultimately led to a healthy live birth. However, none of the mRNA variants identified in the patient showed a strong association with the MEN1 gene.ConclusionsApplying the new rsERT along with PGT improved ART outcomes and brought awareness of the importance of the ER examination in MEN1 infertile female patients. MEN1-induced endocrine disorder rather than MEN1 mutation contributes to the ER abnormality.Trial RegistrationReproductive Medicine Ethics Committee of Xiangya Hospital Registry No.: 2022010.
Case Report: Insulin hypersensitivity in youth with type 1 diabetes
Authors: Alkhatib Einas H. , Grundman Jody B. , Adamusiak Anna M. , Bellin Melena D. , Brooks Joel P. , Buckley Kevin S. , Janssen Erin M. , Kitcharoensakkul Maleewan , McNerney Kyle P. , Pfeifer Thea L. , Polk Brooke I. , Marks Brynn E. 
Published: October 2023

ObjectiveImmediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D).MethodsWe present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic.ResultsInsulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and insulin pump therapy. Multidisciplinary care involving pediatric endocrinology and allergy/immunology utilizing trials of many adjunct therapies yielded minimal improvement. Despite the use of various treatments, including antihistamines, topical therapies, immunosuppressant medications, desensitization trials, and intravenous immune globulin, cutaneous reactions, elevated hemoglobin A1c levels, and negative effects on quality of life remain persistent challenges. One patient became one of the youngest pancreas transplant recipients in the world at age 12 years due to uncontrollable symptoms and intolerable adverse effects of attempted therapies.ConclusionAlthough rare, insulin hypersensitivity reactions negatively affect glycemic control and quality of life. These cases demonstrate the varying severity and presentation of insulin hypersensitivity reactions along with the limited success of various treatment approaches. Given the life-sustaining nature of insulin therapy, further studies are needed to better understand the underlying pathophysiology of insulin hypersensitivity and to develop targeted treatment approaches.
Expanding the genetic and clinical spectrum of osteogenesis imperfecta: identification of novel rare pathogenic variants in type I collagen-encoding genes
Authors: Paduano Francesco , Fischetto Rita , Moretti Biagio , De Vito Danila , Tatullo Marco 
Published: October 2023

IntroductionOsteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder. The majority of affected cases are attributed to autosomal dominant pathogenic variants (PVs) found in the COL1A1 and COL1A2 genes, which encode type I collagen. However, PVs in other genes involved in collagen posttranslational modification, processing, crosslinking, osteoblast differentiation, and bone mineralization have also been associated with OI.MethodsIn this study, we present the results of next-generation sequencing (NGS) analysis using a custom panel of 11 genes known to be associated with OI. This clinical study enrolled a total of 10 patients, comprising 7 male and 3 female patients from 7 families, all from the Puglia Region in South Italy, providing a detailed overview of their age, gender, family history, OI type, and non-skeletal features.ResultsThe genetic analysis revealed 5 PVs in the COL1A1 gene and 2 PVs in the COL1A2 gene. Importantly, three of these PVs have not been previously reported in the literature. These include two novel heterozygous frameshift PVs in COL1A1 (c.2890_2893del and c.3887del) and one novel heterozygous missense PV in COL1A2 (c.596G&gt;T).DiscussionThe identification of these previously unreported PVs expands the variant spectrum of the COL1A1 and COL1A2 genes and may have implications for accurate diagnosis, genetic counselling, and potential therapeutic interventions in affected individuals and their families.
CEP55-associated lethal fetal syndrome: a case report of a Chinese family
Authors: Wang Yeping , Sheng Fang , Ying Lingjing , Lou Qiaoli , Yu Zhaonan , Wang Kaixuan , Wang Haoyi 
Published: October 2023

Background: Research on fetal loss related to germline mutations in single genes remains limited. Disruption of CEP55 has recently been established in association with perinatal deaths characterized by hydranencephaly, renal dysplasia, oligohydramnios, and characteristic dysmorphisms. We herein present a Chinese family with recurrent fetal losses due to compound heterozygous nonsense CEP55 variants.Case presentations: The Chinese couple had a history of five pregnancies, with four of them proceeding abnormally. Two stillbirths (II:3 and II:4) sequentially occurred in the third and fourth pregnancy. Prenatal ultrasound scans revealed phenotypic similarities between fetuses II:3 and II:4, including oligohydramnios, bilateral renal dysplasia and hydrocephalus/hydranencephaly. Clubfoot and syndactyly were also present in both stillborn babies. Fetus II:3 presented with endocardial cushion defects while fetus II:4 did not. With the product of conception in the fourth pregnancy, whole exome sequencing (WES) on fetus II:4 identified compound heterozygous nonsense CEP55 variants comprised of c.190C&gt;T(p.Arg64*) and c.208A&gt;T(p.Lys70*). Both variants were expected to result in lack of the TSG101 and ALIX binding domain. Sanger sequencing confirmed the presence and cosegregation of both variants.Conclusion: This is the fifth reported family wherein biallelic CEP55 variants lead to multiple perinatal deaths. Our findings, taken together with previously described phenotypically similar cases and even those with a milder and viable phenotype, broaden the genotypic and phenotypic spectrum of CEP55-associated lethal fetal syndrome, highlighting the vital biomolecular function of CEP55.
Low-dose decitabine-intensified modified conditioning regimen alleviates aGVHD in AML/MDS patients treated with allogeneic hematopoietic stem cell transplantation
Authors: Zhu Jinye , Wang Qingya , Ren Hanyun , Dong Yujun , Yin Yue , Wang Qian , Liang Zeyin , Liu Wei , Wang Qingyun , Wang Bingjie , Li Yuan 
Published: October 2023

BackgroundThe widespread adoption of Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) has significantly improved the survival rates of patients with hematological malignancies. However, Graft-Versus-Host Disease (GVHD) remains a formidable complication, threatening patient prognosis. Recent research has indicated that decitabine (DAC), known for its hypomethylating properties may also exhibit immune-regulatory capabilities and a potential for reducing GVHD incidence and enhancing survival.MethodsWe retrospectively reviewed data from AML/MDS patients who underwent Allo-HSCT at our center from January 2010 to January 2023. From a total of 251 patients with complete data, we employed propensity score matching (PSM) to create 100 matched pairs (200 patients) for comprehensive trial analysis. Patients receiving low-dose DAC-containing regimen were matched with those who did not receive DAC.ResultsPatients in the DAC group exhibited a significantly lower incidence of grade II-IV acute GVHD (aGVHD) compared to non-DAC group (21% vs. 38%, P=0.013). Univariable and multivariable logistic regression analysis demonstrated DAC intervention as a protective factor against grade II-IV aGVHD (P=0.017, OR=0.47, 95% CI 0.23-0.81; P=0.018, OR=0.46, 95% CI 0.24-0.87). Multivariate competing risk regression further supported administration of decitabine as a protective factor against grade II-IV aGVHD (P=0.038, SHR=0.53, 95%CI 0.29-0.97). There was no significant difference between both groups concerning chronic GVHD, infection, disease relapse, overall survival, disease-free survival and GVHD free, relapse free survival. In MRD negative or intermediate risk subgroup, the grade II-IV aGVHD ameliorating effect of DAC was confirmed as well.ConclusionLow-dose DAC-intensified modified conditioning regimen could improve prognosis in AML/MDS Patients treated with allogeneic hematopoietic stem cell transplantation.
Presence of MDSC associates with impaired antigen-specific T cell reactivity following COVID-19 vaccination in cirrhotic patients
Authors: Törnell Andreas , Blick Elin , Al-Dury Samer , Grauers Wiktorin Hanna , Waern Johan , Ringlander Johan , Einarsdottir Sigrun , Lindh Magnus , Hellstrand Kristoffer , Lagging Martin , Martner Anna 
Published: October 2023

Background and aimsCirrhosis entails high risk of serious infections and abated efficiency of vaccination, but the underlying mechanisms are only partially understood. This study aimed at characterizing innate and adaptive immune functions, including antigen-specific T cell responses to COVID-19 vaccination, in patients with compensated and decompensated cirrhosis.MethodsImmune phenotype and function in peripheral blood from 42 cirrhotic patients and 44 age-matched healthy controls were analysed after two doses of the mRNA-based COVID-19 vaccines [BNT162b2 (Pfizer BioNTech) or mRNA-1273 (Moderna)].ResultsCirrhotic patients showed significantly reduced blood counts of antigen-presenting dendritic cells (DC) and high counts of monocytic myeloid-derived suppressor cells (M-MDSC) as compared to healthy controls. In addition, monocytic cells recovered from cirrhotic patients showed impaired expression of the antigen-presenting molecule HLA-DR and the co-stimulatory molecule CD86 upon Toll-like receptor (TLR) stimulation. These features were more prominent in patients with decompensated cirrhosis (Child-Pugh classes B &amp; C). Interestingly, while patients with compensated cirrhosis (Child-Pugh class A) showed an inflammatory profile with myeloid cells producing the proinflammatory cytokines IL-6 and TNF, decompensated patients produced reduced levels of these cytokines. Cirrhotic patients, in particular those with more advanced end-stage liver disease, mounted reduced antigen-specific T cell reactivity to COVID-19 vaccination. Vaccine efficiency inversely correlated with levels of M-MDSC.ConclusionThese results implicate MDSC as mediators of immunosuppression, with ensuing deficiency of vaccine-specific T cell responses, in cirrhosis.
Finetuning of GLIDE stable diffusion model for AI-based text-conditional image synthesis of dermoscopic images
Authors: Shavlokhova Veronika , Vollmer Andreas , Zouboulis Christos C. , Vollmer Michael , Wollborn Jakob , Lang Gernot , Kübler Alexander , Hartmann Stefan , Stoll Christian , Roider Elisabeth , Saravi Babak 
Published: October 2023

BackgroundThe development of artificial intelligence (AI)-based algorithms and advances in medical domains rely on large datasets. A recent advancement in text-to-image generative AI is GLIDE (Guided Language to Image Diffusion for Generation and Editing). There are a number of representations available in the GLIDE model, but it has not been refined for medical applications.MethodsFor text-conditional image synthesis with classifier-free guidance, we have fine-tuned GLIDE using 10,015 dermoscopic images of seven diagnostic entities, including melanoma and melanocytic nevi. Photorealistic synthetic samples of each diagnostic entity were created by the algorithm. Following this, an experienced dermatologist reviewed 140 images (20 of each entity), with 10 samples originating from artificial intelligence and 10 from original images from the dataset. The dermatologist classified the provided images according to the seven diagnostic entities. Additionally, the dermatologist was asked to indicate whether or not a particular image was created by AI. Further, we trained a deep learning model to compare the diagnostic results of dermatologist versus machine for entity classification.ResultsThe results indicate that the generated images possess varying degrees of quality and realism, with melanocytic nevi and melanoma having higher similarity to real images than other classes. The integration of synthetic images improved the classification performance of the model, resulting in higher accuracy and precision. The AI assessment showed superior classification performance compared to dermatologist.ConclusionOverall, the results highlight the potential of synthetic images for training and improving AI models in dermatology to overcome data scarcity.
Pharmacokinetics of immunosuppressive agents during hemoperfusion in a sheep model
Authors: Leber Bettina , Liebchen Uwe , Rohrhofer Lisa , Weber Jennifer , Klaus Teresa , Scheier Joerg , Sucher Robert , Stiegler Philipp 
Published: October 2023

IntroductionHemoadsorption shows promising signals in organ preservation and post lung transplantation. However, its potential impact on the pharmacokinetics of immunosuppressant drugs (ID) is still unknown.MethodsIn this interventional study, CytoSorb® hemoperfusion was tested in healthy sheep (n = 5) against a sham extracorporeal circuit (n = 3). Seven different ID (tacrolimus (TAC), cyclosporin A (CYA), mycophenolate mofetil (MMF), everolimus (EVER), basiliximab (BAS), methylprednisolone (MP) and prednisolone (PRED)) were administered in clinically relevant doses and combinations. Their levels were measured repeatedly in blood samples from the extracorporeal circulation over 6 h following administration. Population pharmacokinetic modeling analysis (NONMEM® 7.5) was performed.ResultsNegligible clearance was observed for PRED and BAS. For all other substances, a saturable adsorption sub-model with linear decrease of the adsorption effect over the adsorbed amount best described the measured concentrations. The maximum absolute adsorbed amounts (95% CI) for TAC, CYA, MMF, EVER, and MP were 0.040 (0.028–0.053), 1.15 (0.39–1.91), 4.17 (2.00–6.35), 0.0163 (0.007–0.026), and 53.4 mg (20.9–85.9), respectively, indicating an adsorption of less than 5% of the daily administered dosages for all investigated substances.DiscussionIn this large animal model, CytoSorb® hemoperfusion appears to have a limited effect on the clearance of tested ID.
Dynamic changes of fecal microbiota in a weight-change model of Bama minipigs
Authors: Zeng Bo , Chen Li , Kong Fanli , Zhang Chengcheng , Chen Long , Qi Xu , Chai Jin , Jin Long , Li Mingzhou 
Published: October 2023

IntroductionObesity is closely related to gut microbiota, however, the dynamic change of microbial diversity and composition during the occurrence and development process of obesity is not clear.MethodsA weight-change model of adult Bama pig (2 years, 58 individuals) was established, and weight gain (27 weeks) and weight loss (9 weeks) treatments were implemented. The diversity and community structures of fecal microbiota (418 samples) was investigated by using 16S rRNA (V3-V4) high-throughput sequencing.ResultsDuring the weight gain period (1~27 week), the alpha diversity of fecal microbiota exhibited a “down-up-down” fluctuations, initially decreasing, recovering in the mid-term, and decreasing again in the later stage. Beta diversity also significantly changed over time, indicating a gradual deviation of the microbiota composition from the initial time point. Bacteroides, Clostridium sensu stricto 1, and Escherichia-Shigella showed positive correlations with weight gain, while Streptococcus, Oscillospira, and Prevotellaceae UCG-001 exhibited negative correlations. In the weight loss period (30~38 week), the alpha diversity further decreased, and the composition structure underwent significant changes compared to the weight gain period. Christensenellaceae R-7 group demonstrated a significant increase during weight loss and showed a negative correlation with body weight. Porphyromonas and Campylobacter were positively correlated with weight loss.DiscussionBoth long-term fattening and weight loss induced by starvation led to substantial alterations in porcine gut microbiota, and the microbiota changes observed during weight gain could not be recovered during weight loss. This work provides valuable resources for both obesity-related research of human and microbiota of pigs.
Methadone maintenance treatment is more effective than compulsory detoxification in addressing gut microbiota dysbiosis caused by heroin abuse
Authors: Yan Peng , Ma Haotian , Tian Wenrong , Liu Jincen , Yan Xinyue , Ma Lei , Wei Shuguang , Zhu Jie , Zhu Yongsheng , Lai Jianghua 
Published: October 2023

IntroductionHeroin use disorder (HUD) is commonly accompanied by gut dysbiosis, but the roles of gut microbiota in HUD treatment, such as compulsory detoxification and methadone maintenance treatment (MMT), remain poorly understood.MethodsIn this study, we performed 16 s rDNA and whole metagenome sequencing to analyze the gut microbial profiles of HUD patients undergoing heroin addiction, heroin withdrawal (compulsory detoxification), and MMT.ResultsOur findings revealed that, compared to healthy controls, microbial diversity was significantly decreased in HUD patients who were in a state of heroin addiction and withdrawal, but not in those receiving MMT. We observed significant alterations in 10 bacterial phyla and 20 bacterial families in HUD patients, while MMT partially restored these changes. Whole metagenome sequencing indicated gut microbiota functions were significantly disrupted in HUD patients experiencing heroin addiction and withdrawal, but MMT was found to almost reverse these dysfunctions. In addition, we identified 24 featured bacteria at the genus level that could be used to effectively distinguish between healthy individuals and those with heroin addiction, heroin withdrawal, or receiving MMT. Furthermore, we found the relative abundance of Actinomyces, Turicibacter and Weissella were positively associated with the Hamilton Depression Scale score in different states of HUD patients.DiscussionThis study provides evidence from the gut microbiota perspective that MMT is a more effective approach than compulsory detoxification for HUD treatment.