bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic APOE4 removal confers cerebrovascular protection despite increased cerebral amyloid angiopathy
Authors: Xiong Monica , Wang Chao , Gratuze Maud , Saadi Fareeha , Bao Xin , Bosch Megan E. , Lee Choonghee , Jiang Hong , Serrano Javier Remolina , Gonzales Ernesto R. , Kipnis Michal , Holtzman David M. 
Published: March 2023

Abstract
Background
Alzheimer Disease (AD) and cerebral amyloid angiopathy (CAA) are both characterized by amyloid-β (Aβ) accumulation in the brain, although Aβ deposits mostly in the brain parenchyma in AD and in the cerebrovasculature in CAA. The presence of CAA can exacerbate clinical outcomes of AD patients by promoting spontaneous intracerebral hemorrhage and ischemia leading to CAA-associated cognitive decline. Genetically, AD and CAA share the ε4 allele of the apolipoprotein E (APOE) gene as the strongest genetic risk factor. Although tremendous efforts have focused on uncovering the role of APOE4 on parenchymal plaque pathogenesis in AD, mechanistic studies investigating the role of APOE4 on CAA are still lacking. Here, we addressed whether abolishing APOE4 generated by astrocytes, the major producers of APOE, is sufficient to ameliorate CAA and CAA-associated vessel damage.

Methods
We generated transgenic mice that deposited both CAA and plaques in which APOE4 expression can be selectively suppressed in astrocytes. At 2-months-of-age, a timepoint preceding CAA and plaque formation, APOE4 was removed from astrocytes of 5XFAD APOE4 knock-in mice. Mice were assessed at 10-months-of-age for Aβ plaque and CAA pathology, gliosis, and vascular integrity.

Results
Reducing the levels of APOE4 in astrocytes shifted the deposition of fibrillar Aβ from the brain parenchyma to the cerebrovasculature. However, despite increased CAA, astrocytic APOE4 removal reduced overall Aβ-mediated gliosis and also led to increased cerebrovascular integrity and function in vessels containing CAA.

Conclusion
In a mouse model of CAA, the reduction of APOE4 derived specifically from astrocytes, despite increased fibrillar Aβ deposition in the vasculature, is sufficient to reduce Aβ-mediated gliosis and cerebrovascular dysfunction.
Sustainability of health services in refugee hosting districts: a qualitative study of health services in three west Nile refugee hosting districts, Uganda
Authors: Komakech Henry , Orach Christopher Garimoi , Atuyambe Lynn M. 
Published: March 2023

Abstract
Background
Humanitarian health assistance programmes have expanded from temporary approaches addressing short-term needs to providing long-term interventions in emergency settings. Measuring sustainability of humanitarian health services is important towards improving the quality of health services in refugee settings.

Objective
To explore the sustainability of health services following the repatriation of refugees from the west Nile districts of Arua, Adjumani and Moyo.

Methods
This was a qualitative comparative case study conducted in three west Nile refugee-hosting districts of Arua, Adjumani, and Moyo. In-depth interviews were conducted with 28 purposefully selected respondents in each of the three districts. Respondents included health workers and managers, district civic leaders, planners, chief administrative officers, district health officers, project staff of aid agencies, refugee health focal persons and community development officers.

Results
The study shows that in terms of organization capacity, the District Health Teams provided health services to both refugee and host communities with minimal support from aid agencies. Health services were available in most former refugee hosting areas in Adjumani, Arua and Moyo districts. However, there were several disruptions notably reduction and inadequate services due to shortage of drugs and essential supplies, lack of health workers, and closure or relocation of health facilities in around former settlements. To minimize disruptions the district health office reorganized health services. In restructuring health services, the district local governments closed or upgraded health facilities to address reduced capacity and catchment population. Health workers employed by aid agencies were recruited into government services while others who were deemed excess or unqualified were laid off. Equipment and machinery including machines and vehicles were transferred to the district health office in specific health facilities. Funding for health services was mainly provided by the Government of Uganda through the Primary Health Care Grant. Aid agencies, however, continued to provide minimal support health services for refugees who remained in Adjumani district.

Conclusion
Our study showed that while humanitarian health services are not designed for sustainability, several interventions continued at the end of the refugee emergency in the three districts. The embeddedness of the refugee health services in the district health systems ensured health services continued through public service delivery structures. It is important to strengthen the capacity of the local service delivery structures and ensure health assistance programmes are integrated into local health systems to promote sustainability.
Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation
Authors: Dong Jing , Buradagunta Christopher Staffi , Zhang Tao , Spellman Stephen , Bolon Yung-Tsi , DeZern Amy E. , Gadalla Shahinaz M. , Deeg H. Joachim , Nazha Aziz , Cutler Corey , Cheng Chao , Urrutia Raul , Auer Paul , Saber Wael 
Published: March 2023

AbstractDespite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM). A random survival forest algorithm was applied to evaluate the prognostic performance of models that include mtDNA mutations alone and combined with MDS- and HCT-related clinical factors. A total of 2666 mtDNA mutations were identified, including 411 potential pathogenic variants. We found that overall, an increased number of mtDNA mutations was associated with inferior transplantation outcomes. Mutations in several frequently mutated mtDNA genes (e.g., MT-CYB and MT-ND5) were identified as independent predictors of OS, RFS, relapse and/or TRM after allo-HCT. Integration of mtDNA mutations into the models based on the Revised International Prognostic Scores (IPSS-R) and clinical factors related to MDS and allo-HCT could capture more prognostic information and significantly improve the prognostic stratification efforts. Our study represents the first WGS effort in MDS receiving allo-HCT and shows that there may be clinical utility of mtDNA variants to predict allo-HCT outcomes in combination with more standard clinical parameters.
CD46 targeted 212Pb alpha particle radioimmunotherapy for prostate cancer treatment
Authors: Li Jun , Huang Tao , Hua Jun , Wang Qiong , Su Yang , Chen Ping , Bidlingmaier Scott , Li Allan , Xie Zhongqiu , Bidkar Anil P. , Shen Sui , Shi Weibin , Seo Youngho , Flavell Robert R. , Gioeli Daniel , Dreicer Robert , Li Hui , Liu Bin , He Jiang 
Published: March 2023

AbstractWe recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated 212Pb, an in vivo generator of alpha-emitting 212Bi and 212Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate, 212Pb-TCMC-YS5. We characterized 212Pb-TCMC-YS5 in vitro and established a safe dose in vivo. We next studied therapeutic efficacy of a single dose of 212Pb-TCMC-YS5 using three prostate cancer small animal models: a subcutaneous mCRPC cell line-derived xenograft (CDX) model (subcu-CDX), an orthotopically grafted mCRPC CDX model (ortho-CDX), and a prostate cancer patient-derived xenograft model (PDX). In all three models, a single dose of 0.74 MBq (20 µCi) 212Pb-TCMC-YS5 was well tolerated and caused potent and sustained inhibition of established tumors, with significant increases of survival in treated animals. A lower dose (0.37 MBq or 10 µCi 212Pb-TCMC-YS5) was also studied on the PDX model, which also showed a significant effect on tumor growth inhibition and prolongation of animal survival. These results demonstrate that 212Pb-TCMC-YS5 has an excellent therapeutic window in preclinical models including PDXs, opening a direct path for clinical translation of this novel CD46-targeted alpha radioimmunotherapy for mCRPC treatment.
Investigating the potential role of swertiamarin on insulin resistant and non-insulin resistant granulosa cells of poly cystic ovarian syndrome patients
Authors: Belani Muskaan A. , Shah Preeti , Banker Manish , Gupta Sarita S. 
Published: March 2023

Abstract
Background and aim
Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance.

Experimental procedure
hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. Cells were grouped as control, PCOS-IR and PCOS-NIR, treated with swertiamarin (66 µM) and metformin (1 mM). Expression of key molecules involved in insulin signaling, fat metabolism, IGF system and steroidogenesis were compared between groups.

Results
Swertiamarin significantly (P < 0.05) reversed the expression of INSR-β, PI(3)K, p-Akt, PKC-ζ, PPARγ, (P < 0.01) IRS (Ser 307) and IGF system in PCOS-IR group and was equally potent to metformin. In the same group, candidate genes viz SREBP1c, FAS, ACC-1 and CPT-1 were down regulated by swertiamarin (P < 0.001) and metformin (P < 0.001). Significant upregulation was demonstrated in expression of StAR, CYP19A1, 17β-HSD and 3β-HSD when treated with swertiamarin (P < 0.01) and metformin (P < 0.01) in PCOS-IR followed by increase in 17β-HSD and 3β-HSD enzyme activity along with estradiol and progesterone secretions. However, swertiamarin did not reveal any effect on PCOS-NIR group as compared to metformin that significantly (P < 0.01) reversed all the parameters related to steroidogenesis and down regulated basal expression of insulin signaling genes.

Conclusion
Swertiamarin, presents itself as a potential fertility drug in hLGCs from PCOS-IR patients.
Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma
Authors: Feng Zheng , Shao Di , Cai Yuhang , Bi Rui , Ju Xingzhu , Chen Dongju , Song Chengcheng , Chen Xiaojun , Li Jin , An Na , Li Yunjin , Zhou Qing , Xiu Zhihui , Zhu Shida , Wu Xiaohua , Wen Hao 
Published: March 2023

Abstract
Background
Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population.

Methods
We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients.

Results
The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p < 0.001; non-BRCA HRR: 88.6% vs 75.4%, p = 0.062). Patients with HRD status positive had significantly improved PFS compared with those with HRD status negative (median PFS: 30.5 months vs. 16.8 months, Log-rank p = 0.001). Even for BRCAwt patients, positive HRD was also associated with better PFS than the HRD-negative group (median: 27.5 months vs 16.8 months, Log-rank p = 0.010). Further, we found patients with pathogenic mutations located in the DNA-binding domain (DBD) of BRCA1 had improved FPS, compared to those with mutations in other domains. (p = 0.03).

Conclusions
The HRD status can be identified as an independent significance in Chinese HGSOC patients treated with first-line platinum-based chemotherapy.
AMH producing purely cystic virilizing adult granulosa cell tumor in 17 years old girl: a case report and review of literatures
Authors: Kitajima Michio , Kajimura Itsuki , Kitajima Yuriko , Murakami Naoko , Matsumura Asako , Matsumoto Kanako , Harada Ayumi , Hasegawa Yuri , Miura Kiyonori 
Published: March 2023

Abstract
Background
Androgen-producing granulosa cell tumor in adolescent girl is rare condition and clinical characteristics are not fully elucidated.

Case presentation
Seventeen years old girl complained of secondary amenorrhea was referred to our out-patient consultation. Markedly elevated serum testosterone, LH, and AMH levels were noted. Mild hirsutism and clitoromegaly were presented. Transabdominal ultrasonography and MRI revealed cystic mass occupied pelvic cavity probably originated from left ovary. Right ovary showed polycystic appearance. Laparoscopic left ovarian cystectomy was performed. After the surgery, her menstruation resumed along with normalized hormonal parameters, and clinical hyperandrogenism were improved. Since the scarcity of cellular lining of inner cyst wall, definitive pathological diagnosis was difficult. After the consultation with gynecological pathologist, the tumor was diagnosed as sex cord stromal tumor, highly suspicious for adult granulosa cell tumor. Residual left salpingo-oophorectomy was performed by additional laparoscopic surgery. Her serum testosterone and AMH levels were remained low with regular menstrual cycles and no evidence of recurrence.

Conclusions
Androgen-producing cystic granulosa cell tumor is rare gynecological disorders, which need both gynecologic oncological and endocrinological approach. Its clinical manifestations may bring some clues to the pathogenesis of ovulatory dysfunctions, such as polycystic ovary syndrome.
An analysis of risk factors associated with recurrent wheezing in the pediatric population
Authors: Zhu Yibing , Chen Lumin , Miao Yecheng , Chen Jinying , Bai Meng , Gao Haiyan , Zhu Zhirong , Zhang Yuxuan , Zhang Jianzhong , Raza Hafiz Khuram , Liu Guanghua 
Published: March 2023

Abstract
Background
Recurrent wheezing is a common clinical problem in early childhood, which is associated with significant morbidity. There is no international consensus on the management and prevention of recurrent wheezing; therefore, identifying the risk factors associated with recurrent wheezing is crucial to prevent episodes of wheezing in young children.

Methods
In this retrospective study, we collected the data of 24,737 patients who were admitted to our hospital between 27th April 2012 and 11th September 2019. After screening for patients with wheezing, we identified 8572 patients with a primary diagnosis of pneumonia with wheezing. Patients’ clinical data were collected from the hospital medical records. Patients were stratified for age in the groups of < 6 months, 6–12 months, and > 12 months.

Results
Among the 8569 pediatric pneumonia patients with wheezing, there were 343 patients with recurrent wheezing. Most enrolled patients were under 6 months of age (45.17%) and had a normal birth weight (86.95%). Winter was the most common onset season for the first episode of wheezing, while spring was the most common season for the second episode of wheezing for those with recurrent wheezing. The univariate and multivariate logistic regression analysis for the risk factor associated with recurrent wheezing showed that male gender, past history of respiratory and cardiovascular diseases, low birth weight, development of severe pneumonia, and PICU admission were significantly associated with recurrent wheezing.

Conclusion
Male gender, past history of respiratory and cardiovascular diseases, low birth weight, severe pneumonia, and PICU admission are independent risk factors of recurrent wheezing in the pediatric population.
Paraneoplastic pemphigus and Castleman’s disease: a case report and a revision of the literature
Authors: Irrera Mariangela , Bozzola Elena , Cardoni Antonello , DeVito Rita , Diociaiuti Andrea , El Hachem Maya , Girardi Katia , Marchesi Alessandra , Villani Alberto 
Published: March 2023

Abstract
Background
In literature, a few reports described an association between paraneoplastic pemphigus (PNP) and Castelman’s disease (CD), but no consensus have been proposed for the diagnostic-therapeutical approach. Aim of this study is to present a case report and explore the relationship between PNP and CD in pediatric patients, focusing on clinical manifestations, histopathological findings, treatment and outcome to find elements for an early diagnosis.

Case presentation
We present the clinical case of a 13 years old girl with a challenging diagnosis of PNP and CD who underwent therapy at first with Rituximab and then with Siltuximab, for the control of symptoms.

Conclusions
Reviewing literature, 20 clinical cases have been described in the pediatric age. Diagnosis may be challenging, requiring an average of 3 months (range from 3 weeks to 2 years). In all cases, the initial manifestations were mucocutaneous lesions, especially oral lesions with poor response to conventional treatment. Systemic symptoms may be present as well. Therapeutical approach is still discussed with no consensus. Almost all patients received corticosteroids with poor response. Other drugs including azathioprine, methotrexate, cyclosporine and monoclonal antibodies have been evaluated for the control of the disease. Further studies and experimental trials urge to define the diagnostic criteria and therapy protocol.
Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients
Authors: da Cruz Mônica Rodrigues , Camilo Luciana Moisés , da Costa Xavier Tiago Batista , da Motta Ribeiro Gabriel Casulari , Medeiros Denise Machado , da Fonseca Reis Luís Felipe , da Silva Guimarães Bruno Leonardo , Japiassú André Miguel , Carvalho Alysson Roncally Silva 
Published: March 2023

Abstract
Background
The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients.

Methods
Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT).

Results
184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation.

Conclusions
A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.
The Role of Transcriptomics in Redefining Critical Illness
Authors: Pelaia Tiana M. , Shojaei Maryam , McLean Anthony S. 
Published: March 2023

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Interrogating the sepsis host immune response using cytomics
Authors: Lindell Robert B. , Meyer Nuala J. 
Published: March 2023

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online athttps://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available fromhttps://link.springer.com/bookseries/8901.
Hemodynamic Implications of Prone Positioning in Patients with ARDS
Authors: Lai Christopher , Monnet Xavier , Teboul Jean-Louis 
Published: March 2023

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Update on the management of acute respiratory failure using non-invasive ventilation and pulse oximetry
Authors: Abe Tatsuhiko , Takagi Toshishige , Fujii Tomoko 
Published: March 2023

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Managing the Physiologically Difficult Airway in Critically Ill Adults
Authors: Jabaley Craig Steven 
Published: March 2023

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
Setting and Monitoring of Mechanical Ventilation During Venovenous ECMO
Authors: Assouline Benjamin , Combes Alain , Schmidt Matthieu 
Published: March 2023

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.