bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mobile-assisted voice condition analysis system for Parkinson’s disease: assessment of usability conditions
Authors: Carrón Javier , Campos-Roca Yolanda , Madruga Mario , Pérez Carlos J. 
Published: November 2021

Abstract
Background and objective
Automatic voice condition analysis systems to detect Parkinson’s disease (PD) are generally based on speech data recorded under acoustically controlled conditions and professional supervision. The performance of these approaches in a free-living scenario is unknown. The aim of this research is to investigate the impact of uncontrolled conditions (realistic acoustic environment and lack of supervision) on the performance of automatic PD detection systems based on speech.

Methods
A mobile-assisted voice condition analysis system is proposed to aid in the detection of PD using speech. The system is based on a server–client architecture. In the server, feature extraction and machine learning algorithms are designed and implemented to discriminate subjects with PD from healthy ones. The Android app allows patients to submit phonations and physicians to check the complete record of every patient. Six different machine learning classifiers are applied to compare their performance on two different speech databases. One of them is an in-house database (UEX database), collected under professional supervision by using the same Android-based smartphone in the same room, whereas the other one is an age, sex and health-status balanced subset of mPower study for PD, which provides real-world data. By applying identical methodology, single-database experiments have been performed on each database, and also cross-database tests. Cross-validation has been applied to assess generalization performance and hypothesis tests have been used to report statistically significant differences.

Results
In the single-database experiments, a best accuracy rate of 0.92 (AUC = 0.98) has been obtained on UEX database, while a considerably lower best accuracy rate of 0.71 (AUC = 0.76) has been achieved using the mPower-based database. The cross-database tests provided very degraded accuracy metrics.

Conclusion
The results clearly show the potential of the proposed system as an aid for general practitioners to conduct triage or an additional tool for neurologists to perform diagnosis. However, due to the performance degradation observed using data from mPower study, semi-controlled conditions are encouraged, i.e., voices recorded at home by the patients themselves following a strict recording protocol and control of the information about patients by the medical doctor at charge.
Prodrug polymeric micelles integrating cancer-associated fibroblasts deactivation and synergistic chemotherapy for gastric cancer
Authors: Zheng Sheng , Wang Jiafeng , Ding Ning , Chen Wenwen , Chen Hongda , Xue Meng , Chen Fei , Ni Jiaojiao , Wang Zhuo , Lin Zhenghua , Jiang Haiping , Liu Xiangrui , Wang Liangjing 
Published: November 2021

Abstract
Background
The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy.

Methods
Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo.

Results
Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC.

Conclusion
TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC.

Graphical Abstract
The altered immunological status of children conceived by assisted reproductive technology
Authors: Xu Xin , Wu Han , Bian Yuehong , Cui Linlin , Man Yuanyuan , Wang Zhao , Zhang Xin , Zhang Changming , Geng Ling 
Published: November 2021

Abstract
Background
With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring.

Methods
A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads.

Results
Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = − 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05).

Conclusions
Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.
Characteristics of the cytoplasmic halo during fertilisation correlate with the live birth rate after fresh cleaved embryo transfer on day 2 in minimal ovarian stimulation cycles: a retrospective observational study
Authors: Ezoe Kenji , Miki Tetsuya , Okimura Tadashi , Uchiyama Kazuo , Yabuuchi Akiko , Kobayashi Tamotsu , Kato Keiichi 
Published: November 2021

Abstract
Background
Information regarding the influence of cytoplasmic events during fertilisation on the clinical outcome remains limited. The cytoplasmic halo is one of these events. A previous study that used time-lapse technology found an association of the presence and morphokinetics of the cytoplasmic halo with cleavage patterns, development to the blastocyst stage, and the ongoing pregnancy rate after blastocyst transfer. Therefore, the cytoplasmic halo may be a useful predictor of the pregnancy outcome after cleaved embryo transfer. This study evaluated the ability of the cytoplasmic halo to predict a live birth after fresh cleaved embryo transfer on day 2, and sought to identify factors potentially influencing the presence and morphokinetics of the halo.

Methods
A total of 902 embryos cultured in the EmbryoScope+® time-lapse system and subjected to single fresh cleaved embryo transfer were retrospectively analysed. The presence and duration of a cytoplasmic halo were annotated. The initial positions of the pronuclei were also observed. The correlation between the cytoplasmic halo and live birth was evaluated and the association of the cytoplasmic halo with patient, cycle, and embryonic characteristics was determined.

Results
Absence of a cytoplasmic halo was associated with a significant decrease in the likelihood of a live birth after fresh cleaved embryo transfer. Prolongation of the halo, especially the duration of central repositioning of cytoplasmic granules, had an adverse impact on the live birth rate. The characteristics of the cytoplasmic halo were not affected by the ovarian stimulation method used, female age, the serum steroid hormone level on the day of trigger, or semen quality. However, the cytoplasmic halo was significantly affected by male age, oocyte diameter, and the initial position of the male pronucleus.

Conclusions
Absence or prolongation of the cytoplasmic halo was negatively correlated with the live birth rate after fresh cleaved embryo transfer. The characteristics of the cytoplasmic halo were strongly associated with oocyte diameter, male age, and the initial position of the male pronucleus. These findings indicate that the characteristics of the cytoplasmic halo can be used to select more competent embryos for transfer at the cleavage stage.
PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes
Authors: Wang Cuizhe , Chu Xiaolong , Deng Yuchun , Wang Jingzhou , Qiu Tongtong , Zhu Jiaojiao , Yang Xin , Pan Chongge , Xiong Jianyu , Xie Jianxin , Chang Yongsheng , Zhang Jun 
Published: November 2021

Abstract
Background
Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism.

Methods
Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors.

Results
KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 μM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 μM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn’t contribute to PA or OA-induced KLF15 reduction.

Conclusions
Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK.
Transit time flow measurement predicts graft patency in off-pump coronary artery bypass grafting upon 5-year angiographic follow-up
Authors: Zeng Caiwu , Li Xiaomi , Dai Yan , Zhou Ye , Li Chenglong , Liu Nan , Wang Jiangang 
Published: November 2021

Abstract
Objective
This retrospective study sought to evaluate the efficacy of transit time flow measurement (TTFM) as a means of predicting bypass graft patency as assessed by coronary artery angiography upon 5-year follow-up.

Methods
Of 311 patients undergone isolated off-pump coronary artery bypass graft surgery from January 2014 through December 2014, 202 (65%) underwent both intraoperative TTFM and angiography at follow-up. 610 grafts, 202 left internal mammary artery grafts and 408 saphenous vein grafts were checked. Any grafts that exhibited Fitzgibbon type B or O lesions upon angiographic evaluation were considered to be failing. Receiver operating characteristic curves were used to identify the optimal TTFM values for predicting graft patency.

Results
A total of 610 grafts were included in this analysis, including 202 LIMA grafts and 408 SV grafts, of which 107, 129, 129, and 43 anastomosed to DIAG, OM, PDA, and PLA, respectively. LIMA, DIAG, OM, PDA, and PLA bypass grafts had overall patency rates of 95.0%, 74.8%, 73.6%, 71.5%, and 74.4%, respectively, upon 5-year follow up. No significant differences in TTFM values (MGF, PI, and DF) were observed when comparing outcomes associated with individual or sequential SV grafting. MGF was found to be predictive of graft failure regardless of the target vessel (P < 0.05). While PI was found to predict LIMA, OM, and PDA graft failure (P < 0.05), it was not associated with the failure of grafts associated with DIAG and PLA vessels. Similarly, DF was found to predict OM and PDA graft failure (P < 0.05), but was not significantly associated with the failure of grafts associated with LIMA, DIAG, or PLA vessels.

Conclusion
LIMA bypass grafts were associated with better 5-year graft patency relative to SV bypass grafts. Similar graft patency rates were observed for both individual and sequential bypass grafts. MGF was able to predict bypass graft failure in patients that underwent off-pump CABG surgery.
Flow reserve fraction: the optimal choice in lesion assessing and interventional guiding for patient with unstable angina pectoris and intermediate lesion wrapped with myocardial bridge: a case report
Authors: Hu Yuecheng , Cong Hongliang , Zheng Liuying , Jin Dongxia 
Published: November 2021

Abstract
Background
It is difficult to choose correctly interventional strategy for coronary intermediate lesions combined with myocardial bridge. Endovascular imaging is advocated to guide treatment, but flow reserve fraction (FFR) is not recommended to guide the interventional treatment of myocardial bridge disease because of the inaccurate judgment misled by myocardial bridge.

Case presentation
In this study, we reported a case of a 56-year-old male patient with unstable angina pectoris (UAP). From his coronary angiography, we found diffuse stenosis near the midsection of the left anterior descending (LAD) branch and the presence of a severe myocardial bridge in the lesion area. We were sure that the LAD was culprit vessel and this lesion was culprit lesion. Both FFR and intravenous ultrasound (IVUS) were performed and the conclusions of them are different. Although stent implantation is not usually recommended in the myocardial bridge area. However, after careful examination, a stent was finally implanted under the precise guidance of FFR. And the patient recovered well up-to now.

Conclusions
This case illustrates that FFR functional test was complimentary to intravascular imaging test for the coronary intermediate lesion, especially the lesion wrapped with myocardial bridges, both in assessing the lesion and in guiding treatment.
Neonatal repair of total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome: a case report
Authors: Ito Takahiro , Hagino Ikuo , Aoki Mitsuru , Umezu Kentaro , Saito Tomohiro , Suzuki Akiyo 
Published: November 2021

Abstract
Background
Total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome is extremely rare.

Case presentation
We present a case of total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome in a patient who was diagnosed based on transthoracic echocardiography and computed tomography. We observed complete absence of the lung, the bronchial tree, and vascular structures on the right side, with abnormal drainage of the left pulmonary veins into the innominate vein. The patient showed clear clinical evidence of pulmonary venous obstruction and underwent surgery 3 days after birth. The pulmonary venous chamber containing the vertical vein was anastomosed to the left atrium using 7–0 PDS running sutures via a median sternotomy. Echocardiography and computed tomography performed 1 year postoperatively revealed no pulmonary venous obstruction.

Conclusion
We report a rare case of total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome, which was successfully repaired 3 days after birth. A median sternotomy is a safe and effective approach for surgical repair of congenital heart disease with unilateral lung agenesis. Repair of the supra cardiac total anomalous pulmonary connection using the vertical vein is feasible in patients with a small pulmonary venous chamber.
Long-term outcomes of pericardial strip versus prosthetic ring annuloplasty for secondary tricuspid regurgitation by a minimally invasive approach
Authors: Nasso Giuseppe , Di Bari Nicola , Santarpino Giuseppe , Moscarelli Marco , Siro Brigiani Mario , Condello Ignazio , Bartolomucci Francesco , Speziale Giuseppe 
Published: November 2021

Abstract
Background
This study was conducted to compare the outcomes of prosthetic ring versus autologous pericardial strip for the treatment of functional tricuspid regurgitation during left-sided valve surgery by minimally invasive approach.

Methods
From January 2008 and July 2016, autologous pericardial strip (group P-TAP) was used in 109 patients, and prosthetic ring (group R-TAP) in 115 patients. The primary outcomes were long-term overall survival, development of patch degeneration, and significant tricuspid regurgitation recurrence. The second outcome was the assessment of right ventricular functional parameters.

Results
Operative mortality was 1 case (0.9%) in the R-TAP group. At the time of hospital discharge only one patient (0.9%) in the R-TAP group had grade III+ tricuspid regurgitation, and none had grade IV+. Mean follow-up was 94.1 ± 24.5 months. Mild and moderate tricuspid regurgitation recurrence was 3.7% and 4.5% (P-TAP vs. R-TAP groups, p = 0.99). Severe regurgitation was observed in 1.8% of cases only in the R-TAP group (p = 0.49). There were no reoperations. Late mortality was 3.7% and 5.4% (P-TAP vs. R-TAP groups, p = 0.75). Freedom from death, all causes, were comparable among groups (log-rank p = 0.45). There were no statistically significant differences between two groups in TAPSE, left ventricular end-diastolic diameter, left ventricular ejection fraction, and left atrial diameter.

Conclusions
Tricuspid annuloplasty using an autologous pericardial strip in patients undergoing minimally invasive surgery is associated to similar long results (survival, late tricuspid regurgitation, and functional echocardiographic parameters) than annuloplasty with a prosthetic ring. In particular, the pericardial strip over time does not develop any degeneration or retraction.
The use of medical cannabis in pediatric palliative care: a case series
Authors: Divisic Antuan , Avagnina Irene , De Tommasi Valentina , Santini Anna , Brogelli Laura , Giacomelli Luca , Benini Franca 
Published: November 2021

Abstract
Background
Medical cannabis may be a useful tool for managing treatment-resistant epilepsy and chronic pain, which affect many patients in pediatric palliative care (PPC); however, little evidence is available in this setting.

Case presentation
We aimed to describe a clinical experience in a setting where high-level evidence may not be obtained. We report our clinical experience in a pediatric palliative care department in Italy. Caregivers reported changes in intensity and frequency of pain and epilepsy events. Six patients received a titrated plant extract of cannabis sativa for 1 year. Only mild and transient adverse events occurred: drowsiness, euphoria, restlessness and tachycardia; the resolution was either spontaneous or obtained by modifying the administration schedule. Treatment was never discontinued. No overdoses occurred. All patients experienced seizures during the pre-treatment observation period, and obtained a reduction in seizure frequency, although with variable extent while receiving cannabis. In addition, a benefit on pain was observed, based on the caregiver’s evaluation, and a reduction of analgesic use.

Conclusion
Our experience suggests that a titrated plant extract preparation of medical cannabis may be useful to control treatment-resistant pain and epilepsy in PPC patients.
Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients
Authors: Zeng Cong , Evans John P. , Reisinger Sarah , Woyach Jennifer , Liscynesky Christina , Boghdadly Zeinab El , Rubinstein Mark P. , Chakravarthy Karthik , Saif Linda , Oltz Eugene M. , Gumina Richard J. , Shields Peter G. , Li Zihai , Liu Shan-Lu 
Published: November 2021

AbstractThere is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin’s lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT50) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT50 levels, with 50-60% of them below the detection limit; (3) mean NT50 levels in patients with CLL and NHL was ~2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT50 levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.