bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany
Authors: Bühler Klaus F. , Fischer Robert , Verpillat Patrice , Allignol Arthur , Guedes Sandra , Boutmy Emmanuelle , Bilger Wilma , Richter Emilia , D’Hooghe Thomas 
Published: June 2021

Abstract
Background
This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany.

Methods
Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle).

Results
Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP.

Conclusions
This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.
Advancing our understanding of HIV co-infections and neurological disease using the humanized mouse
Authors: Endsley Janice J. , Huante Matthew B. , Naqvi Kubra F. , Gelman Benjamin B. , Endsley Mark A. 
Published: June 2021

AbstractHumanized mice have become an important workhorse model for HIV research. Advances that enabled development of a human immune system in immune deficient mouse strains have aided new basic research in HIV pathogenesis and immune dysfunction. The small animal features facilitate development of clinical interventions that are difficult to study in clinical cohorts, and avoid the high cost and regulatory burdens of using non-human primates. The model also overcomes the host restriction of HIV for human immune cells which limits discovery and translational research related to important co-infections of people living with HIV. In this review we emphasize recent advances in modeling bacterial and viral co-infections in the setting of HIV in humanized mice, especially neurological disease, andMycobacterium tuberculosisand HIV co-infections. Applications of current and future co-infection models to address important clinical and research questions are further discussed.
Repeated oral administration of low doses of silver in mice: tissue distribution and effects on central nervous system
Authors: Recordati Camilla , De Maglie Marcella , Cella Claudia , Argentiere Simona , Paltrinieri Saverio , Bianchessi Silvia , Losa Marco , Fiordaliso Fabio , Corbelli Alessandro , Milite Gianpaolo , Aureli Federica , D’Amato Marilena , Raggi Andrea , Cubadda Francesco , Soldati Sabina , Lenardi Cristina , Scanziani Eugenio 
Published: June 2021

Abstract
Background
Widespread use of silver in its different forms raises concerns about potential adverse effects after ingestion, the main exposure route for humans. The aim of this study was to investigate in CD-1 (ICR) male mice the tissue distribution and in vivo effects of 4-week oral exposure to 0.25 and 1 mg Ag/kg bw 10 nm citrate coated silver nanoparticles (AgNPs) and 1 mg Ag/kg bw silver acetate (AgAc) at the end of treatment (EoT) and after 4 weeks of recovery.

Results
There were no treatment-related clinical signs and mortality, and no significant effects on body and organ weights at the EoT and after recovery. Treatment-related changes in hematology and clinical chemistry were found after recovery, the most relevant being a dose-dependent lymphopenia and increased triglycerides in AgNP-treated mice, and increased levels of urea in all treated groups, associated with decreased albumin only in AgAc-treated mice. At the EoT the highest silver concentration determined by Triple Quadrupole ICP-MS analysis was found in the brain, followed by testis, liver, and spleen; much lower concentrations were present in the small intestine and kidney. Tissue silver concentrations were slightly higher after exposure to AgAc than AgNPs and dose dependent for AgNPs. After recovery silver was still present in the brain and testis, highlighting slow elimination. No histopathological changes and absence of silver staining by autometallography were observed in the organs of treated mice. At the EoT GFAP (astrocytes) immunoreactivity was significantly increased in the hippocampus of AgNP-treated mice in a dose-dependent manner and Iba1 (microglial cells) immunoreactivity was significantly increased in the cortex of 1 mg/kg bw AgNP-treated mice. After recovery, a significant reduction of Iba1 was observed in the cortex of all treated groups. TEM analysis of the hippocampus revealed splitting of basement membrane of the capillaries and swelling of astrocytic perivascular end-feet in 1 mg/kg bw AgNP- and AgAc-treated mice at the EoT.

Conclusions
Our study revealed accumulation and slow clearance of silver in the brain after oral administration of 10 nm AgNPs and AgAc at low doses in mice, associated with effects on glial cells and ultrastructural alterations of the Blood-Brain Barrier.
How to deal with the consent of adults with cognitive impairment involved in European geriatric living labs?
Authors: Sacco Guillaume , Noublanche Frédéric , Blazek Frédéric , Hue Catherine , Carballido Loïc , Asfar Marine , Allain Philippe , Annweiler Cédric 
Published: June 2021

Abstract
Background
Living labs are realistic environments designed to create links between technology developers and end-users (i.e. mostly older adults). Research in LLH (Living labs in health) covers a wide range of studies from non-interventional studies to CT (clinical trials) and should involve patients with neurocognitive disorders. However, the ethical issues raised by the design, development, and implementation of research and development projects in LLH have been the subject of only little interest thus far.

Objective
Our aim was to determine a pragmatic, ethical and regulatory correct approach to seek the informed consent of patients with neurocognitive disorders according to the different types of studies carried out in European LLH, with a focus on the French context.

Methods
A narrative review of regulatory texts and clinical articles was conducted, and a pragmatic procedure to determine the decision-making capacity of older adults in LLH was proposed.

Results
Individuals must be adequately informed and freely agree to participate in CT. The capacity to consent should be assessed in CT including cognitively impaired older adults. We propose the following steps: first to assess for delirium using the 4 ‘A’s Test (4AT) or the 3-min Diagnostic interview for Confusion Assessment Method (3D-CAM), second to search for medical history of major neurocognitive disorder, and third to assess the decision capacity using the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC).

Conclusions
Including individuals with neurocognitive disorders in research implies using an efficient and pragmatic strategy to inform participants and obtain their consent. The tool we offer here may be useful in the routine operation of LLH but can also be extended to all CT with this population.
Increased acromiohumeral distance in a double-row arthroscopic rotator cuff surgery compared to a single-row surgery after 12 months
Authors: Turan Kaya , Çabuk Haluk , Köroğlu Cenk , Öztürk Çağatay 
Published: June 2021

Abstract
Background
Arthroscopic rotator cuff surgery is an effective treatment for rotator cuff tears with the considered use of double-row repair techniques becoming popular in the last decade. We aim to compare the effects of double- and single-row arthroscopic rotator cuff repairs (ARCR) on repair integrity (RI) and acromiohumeral distance (AHD).

Methods
In this observational study, we retrospectively identified 98 patients with degenerative rotator cuff tear treated with arthroscopic rotator cuff repair between 2016 and 2019. We excluded 22 patients with partial-thickness tears, 15 with associated subscapularis or SLAP tears, 13 with massive tears, and 5 patients lost to follow-up; we included 43 patients who had ARCR for full-thickness cuff tear and clinical, radiologic follow-up. Of these 43 patients, 23 are grouped as double-row repair group (DRG) and 20 as single-row repair group (SRG). A minimum of 12 months after the surgery, bilateral shoulder MRIs were obtained. Contralateral shoulders without asymptomatic rotator cuff tears served as a control group (CG). The operating surgeon and two other surgeons experienced in arthroscopy blindly measured the AHD and determined the RI at the control MRIs in all groups. Functional assessments relied on UCLA and qDASH Scores.

Results
The mean age was 57.89 (45–78) years, and the mean follow-up time was 28,65 (21–43) months. The mean AHD of the CG was 9.7 ± 0.96 mm, the preoperative AHD of DRG was 8.62 ± 1.45 mm, and SRG was 9.71 ± 0.95 mm. The postoperative mean AHD of DRG 9.61 ± 1.83 mm and SRG was 10.21 ± 1.97 mm. AHD differences between the preoperative and postoperative groups were significant (P=0.009). The increase of the AHD in the double-row group was significantly higher than the single-row group (P=0.004). There was a high correlation between the RI and DASH scores (P=0.005). RI did not correlate with the repair method (P=0.580).

Conclusion
Although double-row repairs can maintain greater AHD than single-row repairs in the clinical setting, this difference did not affect functional results. Regardless of the surgical intervention, functional results are favourable if RI is achieved.

Level of evidence
Level III, Retrospective Cohort Study
The comparison between anterior and posterior approaches for removal of infected lumbar interbody cages and a proposal regarding the use of endoscope-assisted technique
Authors: Li Yun-Da , Chi Jia-En , Chiu Ping-Yeh , Kao Fu-Cheng , Lai Po-Liang , Tsai Tsung-Ting 
Published: June 2021

Abstract
Background
In cases of postoperative deep wound infection after interbody fusion with cages, it is often difficult to decide whether to preserve or remove the cages, and there is no consensus on the optimal approach for removing cages. The aim of this study was to investigate the surgical management of cage infection after lumbar interbody fusion.

Methods
A retrospective study was conducted between January 2012 and August 2018. Patients were included if they had postoperative deep wound infection and required cage removal. Clinical outcomes, including operative parameters, visual analog scale, neurologic status, and fusion status, were assessed and compared between anterior and posterior approaches for cage removal.

Results
Of 130 patients who developed postoperative infection and required surgical debridement, 25 (27 levels) were diagnosed with cage infection. Twelve underwent an anterior approach, while 13 underwent cage removal with a posterior approach. Significant differences were observed between the anterior and posterior approaches in elapsed time to the diagnosis of cage infection, operative time, and hospital stay. All patients had better or stationary American Spinal Injury Association impairment scale, but one case of recurrence in adjacent disc 3 months after the surgery.

Conclusions
Both anterior and posterior approaches for cage removal, followed by interbody debridement and fusion with bone grafts, were feasible methods and offered promising results. An anterior approach often requires an additional extension of posterior instrumentation due to the high incidence of concurrent pedicle screw loosening. The use of an endoscope-assisted technique is suggested to facilitate safe removal of cages.
Circulating tumor DNA tracking through driver mutations as a liquid biopsy-based biomarker for uveal melanoma
Authors: Bustamante Prisca , Tsering Thupten , Coblentz Jacqueline , Mastromonaco Christina , Abdouh Mohamed , Fonseca Cristina , Proença Rita P. , Blanchard Nadya , Dugé Claude Laure , Andujar Rafaella Atherino Schmidt , Youhnovska Emma , Burnier Miguel N. , Callejo Sonia A. , Burnier Julia V. 
Published: June 2021

Abstract
Background
Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite good primary tumor control, up to 50% of patients develop metastasis, which is lethal. UM often presents asymptomatically and is usually diagnosed by clinical examination and imaging, making it one of the few cancer types diagnosed without a biopsy. Hence, alternative diagnostic tools are needed. Circulating tumor DNA (ctDNA) has shown potential as a liquid biopsy target for cancer screening and monitoring. The aim of this study was to evaluate the feasibility and clinical utility of ctDNA detection in UM using specific UM gene mutations.

Methods
We used the highly sensitive digital droplet PCR (ddPCR) assay to quantify UM driver mutations (GNAQ, GNA11, PLCβ4 and CYSTLR2) in cell-free DNA (cfDNA). cfDNA was analyzed in six well established human UM cell lines with known mutational status. cfDNA was analyzed in the blood and aqueous humor of an UM rabbit model and in the blood of patients. Rabbits were inoculated with human UM cells into the suprachoroidal space, and mutated ctDNA was quantified from longitudinal peripheral blood and aqueous humor draws. Blood clinical specimens were obtained from primary UM patients (n = 14), patients presenting with choroidal nevi (n = 16) and healthy individuals (n = 15).

Results
The in vitro model validated the specificity and accuracy of ddPCR to detect mutated cfDNA from UM cell supernatant. In the rabbit model, plasma and aqueous humor levels of ctDNA correlated with tumor growth. Notably, the detection of ctDNA preceded clinical detection of the intraocular tumor. In human specimens, while we did not detect any trace of ctDNA in healthy controls, we detected ctDNA in all UM patients. We observed that UM patients had significantly higher levels of ctDNA than patients with nevi, with a strong correlation between ctDNA levels and malignancy. Noteworthy, in patients with nevi, the levels of ctDNA highly correlated with the presence of clinical risk factors.

Conclusions
We report, for the first time, compelling evidence from in vitro assays, and in vivo animal model and clinical specimens for the potential of mutated ctDNA as a biomarker of UM progression. These findings pave the way towards the implementation of a liquid biopsy to detect and monitor UM tumors.
Two Fusarium copper radical oxidases with high activity on aryl alcohols
Authors: Cleveland Maria , Lafond Mickael , Xia Fan Roderick , Chung Ryan , Mulyk Paul , Hein Jason E. , Brumer Harry 
Published: June 2021

AbstractBackgroundBiomass valorization has been suggested as a sustainable alternative to petroleum-based energy and commodities. In this context, the copper radical oxidases (CROs) from Auxiliary Activity Family 5/Subfamily 2 (AA5_2) are attractive biocatalysts for the selective oxidation of primary alcohols to aldehydes. Originally defined by the archetypal galactose 6-oxidase fromFusarium graminearum, fungal AA5_2 members have recently been shown to comprise a wide range of specificities for aromatic, aliphatic and furan-based alcohols. This suggests a broader substrate scope of native CROs for applications. However, only 10% of the annotated AA5_2 members have been characterized to date.ResultsHere, we define two homologues from the filamentous fungiFusarium graminearumandF. oxysporumas predominant aryl alcohol oxidases (AAOs) through recombinant production inPichia pastoris, detailed kinetic characterization, and enzyme product analysis. Despite possessing generally similar active-site architectures to the archetypalFgrGalOx,FgrAAO andFoxAAO have weak activity on carbohydrates, but instead efficiently oxidize specific aryl alcohols. Notably, bothFgrAAO andFoxAAO oxidize hydroxymethyl furfural (HMF) directly to 5-formyl-2-furoic acid (FFCA), and desymmetrize the bioproduct glycerol to the uncommon L-isomer of glyceraldehyde.ConclusionsThis work expands understanding of the catalytic diversity of CRO from AA5_2 to include unique representatives fromFusariumspecies that depart from the well-known galactose 6-oxidase activity of this family. Detailed enzymological analysis highlights the potential biotechnological applications of these orthologs in the production of renewable plastic polymer precursors and other chemicals.
Enriched gardens improve cognition and independence of nursing home residents with dementia: a pilot controlled trial
Authors: Bourdon Etienne , Belmin Joël 
Published: June 2021

Abstract
Background
Dementia is a major issue worldwide, and considerable efforts were made to design therapeutic mediation tools and evaluate their benefits on the health of patients.

Methods
Design: Multi-center cluster-controlled pilot trial.
Settings and participants: Four nursing homes that offered separated access to one conventional sensory garden (CSG) and one enriched garden (EG). The participants were residents with dementia, independent for walking and with no severe dementia or behavioural troubles. Eligible residents were divided into three groups according to the proximity of their room: close to the CSG or EG gardens for the first two groups and further from the gardens for the third (control) group.
Interventions: We asked staff members to frequently invite residents to visit the EG or the CSG depending on their group allocation. No invitation to gardens was made to the control group. We installed 12 enrichment modules in the EG that stimulated cognitive, independence and walking/balance functions.
Measures: Cognitive function (MMSE), independence for activities of daily living (ADL) and risk of falls (unipodal stance and timed up and go – (TUG)) were assessed at baseline and after 6 months.

Results
The 120 participants were 81·0 ± 3·5 years old and comprised of 83 women. Their MMSE score was 17·5 ± 2·9. Patients’ characteristics were not significantly different between the three groups. Among the participants invited to visit the EG group, 6-month changes in MMSE showed improvement compared to other groups (+ 0·93 ± 0·65 vs −0·25 ± 0·71 and −0·24 ± 0·73 in the EG vs CSG and control groups, respectively, P < 0·0001). Changes in ADL, TUG and unipodal stance were significantly improved in the group visiting the EG as compared to other groups, which indicates better functioning.

Conclusions
EGs offer a new approach to therapeutic mediation for residents of nursing homes with dementia.
Differential diagnosis of uncommon prostate diseases: combining mpMRI and clinical information
Authors: Han Chao , Zhu Lina , Liu Xiang , Ma Shuai , Liu Yi , Wang Xiaoying 
Published: June 2021

AbstractThe differential diagnosis of abnormalities in the prostate is broad, covering common (acinar adenocarcinoma, benign prostatic hyperplasia, chronic prostatitis, hemorrhage, cysts, calcifications, atrophy and fibrosis) and less common conditions (tumors other than acinar adenocarcinoma, granulomatous prostatitis containing tuberculosis, abscesses and other conditions, and idiopathic disorders such as amyloidosis and exophytic benign prostatic hyperplasia). Recent advances in magnetic resonance imaging (MRI) of the prostate gland and imaging guidelines, such as the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1), have dramatically improved the ability to distinguish common abnormalities, especially the ability to detect clinically significant prostate cancer (csPCa). Overlap can exist in the clinical history and imaging features associated with various common/uncommon prostate abnormalities, and biopsy is often required but is invasive. Prostate abnormalities can be divided into two categories: category 1, diseases for which PI-RADS scores are suitable for use, and category 2, diseases for which PI-RADS scores are unsuitable for use. Radiologists must have an intimate knowledge of other diseases, especially uncommon conditions. Past relevant history, symptoms, age, serum prostate-specific antigen (PSA) levels, MRI manifestations, and the applicability of the PI-RADS assessment should be considered when diagnosing prostate abnormalities.
RETRACTED ARTICLE: Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
Authors: Zhang Ruijie , Li Peng , Lv Heli , Li Nana , Ren Suliang , Xu Wentao 
Published: June 2021

Abstract
Background
Glioma is one of the most common central nervous system malignant tumors, accounting for 45~60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy.

Methods
Long non-coding RNA (lncRNA) SNHG16 expression level was measured by microarray and qRT-PCR assay; ISH was used to identify the location of SNHG16. Cancer stem cells (CSCs) were separated from glioma tissues and identified using immunofluorescence. Exosomes were isolated from CSCs and cancer cells and identified by TEM and western blot. MTT, wound healing, transwell, and colony formation assay were performed to explore the role of SNHG16 or si-SNHG16 from CSCs on progression of glioma cells. RIP was used to verify the interaction between SNHG16 and TLR7. The experiment of Xenograft used for exploring the function of SNHG16/ TLR7/MyD88/NFκB/c-Myc on growth on glioma in vivo.

Results
Microarray assay showed long non-coding RNA (lncRNA) SNHG16 was upregulated in glioma. Followed qRT-PCR also showed an increase of SNHG16 in glioma tissues; high expression of SNHG16 indicated a poor prognosis in glioma patients. Interestingly, SNHG16 was packaged into exosomes and derived from CSCs. Functional analysis showed exo-SNHG16 secreted by CSCs promoted the progression of glioma cell lines SHG44 and U251. Furthermore, SNHG16 interacted with TLR7 and activated NFκB/c-Myc signaling in glioma cells. And the silencing of TLR7 inhibited the progression of SHG44 and U251 cells by exo-SNHG16 from CSCs. In vivo tumorigenesis experiments showed that exo-SNHG16 induced glioma progression by activating TLR7/MyD88/NFκB/c-Myc signaling.

Conclusion
Our study suggested CSC-derived exo-SNHG16 promoted cancer progression by activating TLR7/MyD88/NFκB/c-Myc signaling pathway.