bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between ambient temperature and sperm quality in Wuhan, China
Authors: Wang Xiaochen , Tian Xiaojia , Ye Bo , Zhang Yi , Zhang Xiaotong , Huang Shichun , Li Cunlu , Wu Simin , Li Rui , Zou Yuliang , Liao Jingling , Yang Jing , Ma Lu 
Published: April 2020

Abstract
Background
Few epidemiological investigations have focused on the influence of environmental temperature on human sperm quality. Here, we evaluated the potential association between ambient temperature and human sperm quality in Wuhan, China, and examined the interactive effect of particulate matter (PM2.5) and temperature.

Methods
1780 males who had been living in Wuhan for no less than three months and received semen analysis at the Department of Reproductive Medicine in Renmin Hospital of Wuhan University between April 8, 2013 and June 30, 2015 were recruited. Daily mean meteorological data and air pollution data (PM2.5, O3 and NO2) in Wuhan between 2013 and 2015 were collected. A generalized linear model was used to explore the associations between ambient temperature and sperm quality (including sperm concentration, percentage of normal sperm morphology, and progressive motility) at 0–9, 10–14, 15–69, 70–90, and 0–90 days before semen examination, and the interaction between temperature and PM2.5.

Results
The associations between ambient temperature and sperm quality were an inverted U-shape at five exposure windows, except for a lag of 0–9 days for sperm concentration. A 1 °C increase in ambient temperature above the thresholds was associated with a 2.038 (1.292 ~ 2.783), 1.814 (1.217 ~ 2.411), 1.458 (1.138 ~ 1.777), 0.934(0.617 ~ 1.251) and 1.604 (1.258 ~ 1.951) decrease in the percentage of normal sperm morphology at lag 0–9, lag 10–14, lag 15–69, lag 70–90, and lag 0–90 days, respectively. The interaction p-values of PM2.5 and temperature were mostly less than 0.05 at five exposure windows. When ambient temperature exposure levels were above the thresholds, a 0.979 (0.659–1.299) and 3.559 (0.251 ~ 6.867) decrease in percentage of normal sperm morphology per 1 °C increase in temperature at lag 0–90 days was observed in the PM2.5 ≤ P50 group and PM2.5 > P50 group, respectively.

Conclusions
Our results indicate that exposure to ambient temperature has a threshold effect on sperm quality, and PM2.5 enhances the effect of temperature on sperm quality when temperatures are above the threshold.
RETRACTED ARTICLE: M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3
Authors: Xiong Yuan , Chen Lang , Yan Chenchen , Zhou Wu , Yu Tao , Sun Yun , Cao Faqi , Xue Hang , Hu Yiqiang , Chen Dong , Mi Bobin , Liu Guohui 
Published: April 2020

Abstract
Background
Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo, and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation.

Results
We found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 (SIK2 and SIK3) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo.

Conclusions
Our study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.
Influence of schooling on the health-related quality of life of children with rare diseases
Authors: Paz-Lourido Berta , Negre Francisca , de la Iglesia Begoña , Verger Sebastià 
Published: April 2020

Abstract
Background
Although participation of children with rare diseases in school is considered beneficial, it poses new challenges for the educational system, but also for the affected children and their families. The aim of this study is to identify which aspects of the schooling experience may have an impact on the health-related quality of life of children with rare diseases.

Method
A qualitative study was conducted using the social-critical paradigm as theoretical perspective. Participants (n = 28) included children with rare diseases (n = 8), parents (n = 12) and school staff (n = 8). Data was obtained through in-depth interviews and focus groups and analysed through discourse analysis as methodological orientation.

Results
Participants’ discourses placed value on the social benefits of inclusion of children with rare diseases in schooling. Discourses also highlighted how the low numbers of children with rare diseases and the delay, or lack, of a clear diagnosis are among the difficulties experienced in the pursuit of the adaptations that children and teachers need to promote a healthy and normalized school experience. The issues identified in their health-related quality of life were summarized in seven categories: Attendance, Knowledge, Participation, Acceptance, Discrimination, Safety, Health-Related Support.

Conclusion
Children with rare diseases remain, in many cases, invisible at the educational level due to the low numbers of children affected, limiting the kind of resources available to the child and teaching staff. This situation requires inter-disciplinary and inter-sector measures between health services and educational environments to articulate a comprehensive approach focused on children’s clinical needs.
How personalised medicine will transform healthcare by 2030: the ICPerMed vision
Authors: Vicente Astrid M. , Ballensiefen Wolfgang , Jönsson Jan-Ingvar 
Published: April 2020

AbstractThis commentary presents the vision of the International Consortium for Personalised Medicine (ICPerMed) on how personalised medicine (PM) will lead to the next generation of healthcare by 2030. This vision focuses on five perspectives: individual and public engagement, involvement of health professionals, implementation within healthcare systems, health-related data, and the development of sustainable economic models that allow improved therapy, diagnostic and preventive approaches as new healthcare concepts for the benefit of the public. We further identify four pillars representing transversal issues that are crucial for the successful implementation of PM in all perspectives. The implementation of PM will result in more efficient and equitable healthcare, access to modern healthcare methods, and improved control by individuals of their own health data, as well as economic development in the health sector.
The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route
Authors: Edelman Robert , Deming Meagan E. , Toapanta Franklin R. , Heuser Mark D. , Chrisley Lisa , Barnes Robin S. , Wasserman Steven S. , Blackwelder William C. , Handwerger Barry S. , Pasetti Marcela , Siddiqui Khan M. , Sztein Marcelo B. 
Published: April 2020

Abstract
Background
Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions.

Results
Fifty-two healthy, community dwelling elderly adults (65–82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21–34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly.

Conclusions
Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations.

Clinical trial registration
ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.
2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
Authors: Grünert Sarah C. , Sass Jörn Oliver 
Published: April 2020

AbstractBackground2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations inACAT1.MethodsWe performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.ResultsFor 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities.ConclusionThis comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
Development and validation of next generation sequencing based 35-gene hereditary cancer panel
Authors: Chan Wing , Lee Mianne , Yeo Zhen Xuan , Ying Dingge , Grimaldi Keith A. , Pickering Craig , Yang Michael M. S. , Sundaram Senthil K. , Tzang Lawrence C. H. 
Published: April 2020

Abstract
Background
Understanding the genetic basis of cancer risk is a major international endeavor. The emergence of next-generation sequencing (NGS) in late 2000’s has further accelerated the discovery of many cancer susceptibility genes. The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has proven to be a viable option, with the accurate and robust detection of a wide range of clinically relevant variants in the targeted genes being crucial.

Methods
We have developed and validated a targeted NGS-based test for hereditary cancer risk assessment using Illumina’s NGS platform by analyzing the protein-coding regions of 35 hereditary cancer genes with a bioinformatics pipeline that utilizes standard practices in the field. This 35-gene hereditary cancer panel is designed to identify germline cancer-causing mutations for 8 different cancers: breast, ovarian, prostate, uterine, colorectal, pancreatic, stomach cancers and melanoma. The panel was validated using well-characterized DNA specimens [NIGMS Human Genetic Cell Repository], where DNA had been extracted using blood of individuals whose genetic variants had been previously characterized by the 1000 Genome Project and the Coriell Catalog.

Results
The 35-gene hereditary cancer panel shows high sensitivity (99.9%) and specificity (100%) across 4820 variants including single nucleotide variants (SNVs) and small insertions and deletions (indel; up to 25 bp). The reproducibility and repeatability are 99.8 and 100%, respectively.

Conclusions
The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has been considered a viable option. In the present study, we developed and validated a 35-gene panel for testing 8 common cancers using next-generation sequencing (NGS). The performance of our hereditary cancer panel is assessed across a board range of variants in the 35 genes to support clinical use.
Influenza infection elicits an expansion of gut population of endogenous Bifidobacterium animalis which protects mice against infection
Authors: Zhang Qiang , Hu Jin , Feng Jia-Wu , Hu Xiao-Tong , Wang Ting , Gong Wen-Xiao , Huang Kun , Guo Yi-Xiong , Zou Zhong , Lin Xian , Zhou Run , Yuan Yu-Qi , Zhang An-Ding , Wei Hong , Cao Gang , Liu Chen , Chen Ling-Ling , Jin Mei-Lin 
Published: April 2020

Abstract
Background
Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism.

Results
Transferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mock-infected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect.

Conclusions
These findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.
The MiLES intervention targeting employers to promote successful return to work of employees with cancer: design of a pilot randomised controlled trial
Authors: Greidanus Michiel A. , de Boer Angela G. E. M. , de Rijk Angelique E. , Frings-Dresen Monique H. W. , Tamminga Sietske J. 
Published: April 2020

Abstract
Background
Employers express a need for support to facilitate the return to work (RTW) process of employees with cancer. We have developed the MiLES intervention, an online toolbox targeting employers during the RTW of employees with cancer. To evaluate the MiLES intervention, we propose the design of a pilot randomised controlled trial (RCT). The aim of this pilot is to determine whether a future RCT to study the effectiveness of this intervention on successful RTW of employees with cancer is feasible. Secondary aims are to obtain preliminary results on the effectiveness of the intervention and to determine the sample size needed in a future definitive RCT.

Methods
A pilot RCT with a 6-month follow-up will be conducted. Using medical specialists at Dutch hospitals, we aim to enrol 90 participants diagnosed with cancer (<2 years earlier) aged 18–63 years who are in paid employment with an employer and who are currently sick-listed or partly sick-listed for <1 year. Participants randomised to the intervention group will be asked to inform their employer about the online toolbox supporting employers during the RTW process of employees with cancer. Participants in the control group will receive ‘care as usual’ from their employer. All measures will be assessed at the level of the employee using questionnaires at baseline and after 3 and 6 months of follow-up. The feasibility of a future RCT will be determined using criteria concerning method-related uncertainties and acceptability of the study protocol. The primary effect measure will be successful RTW (that is, RTW perceived as being successful by the cancer survivor themselves). This effect measure will be used to perform the sample size calculation for a future definitive RCT.

Discussion
The design is proposed to determine the feasibility to study the effectiveness of the MiLES intervention targeting employers on the successful RTW of employees diagnosed with cancer. This pilot RCT can increase the probability of a successful future definitive RCT on the effectiveness of the intervention and potentially obviate the need to carry out an unfeasible and resource-intensive study.

Trial registration
Dutch Trial Register (NTR): NL6758, NTR7627. Registered on 30 October 2018.
Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis: study protocol for a multicenter, prospective, randomized controlled trial
Authors: Wang Wenwen , Ma Xiangyi , Zhang Wei , Li Zhiying , Wang Yan , Yu Zhiying , Zhang Chunlian , Hong Li , Luo Ruoyu , Xing Hui , Wang Wuliang , Yue Qingfen , Wei Jia , Zhang Minli , Wang Shixuan 
Published: April 2020

Abstract
Background
The preservation of fertility and integrity of the reproductive organs has increasingly been of concern to most women with adenomyosis. Adenomyomectomy is conservative surgery that is now widely applied; however, relapse is a serious problem after the operation. Postoperative treatment, such as gonadotropin-releasing hormone agonist (GnRHa) has been suggested to result in reducing the rate of disease recurrence. However, there is still a lack of evidence from randomized clinical trials examining the efficacy of GnRHa in decreasing the postoperative recurrence rate.

Method/design
Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis is a multicenter, prospective, randomized controlled trial. The primary outcome is relapse assessed using a visual analogue scale (VRS) and numeric rating scale (NRS), pictorial blood loss assessment chart (PBAC) score, and the size of the uterus and the lesion as measured by two/three-dimensional color doppler ultrasonography (2D/3D-CDUS) or magnetic resonance imaging (MRI). The secondary outcomes include quality of life, clinical pregnancy, ovarian reserve, adverse events, assessment by the Short Form (36) Health Survey and Female Sexual Function index, serum follicle-stimulating hormone, estradiol levels, and anti-Muellerian hormone and so on. All these indexes are measured at 3, 6, 12, 18, 24, 30, and 36 months after conservative surgery.

Discussion
The result of this large, multicenter randomized trial will provide evidence for one of the strategies of long-term management in focal adenomyosis after conservative operation.

Trial registration
Chinese Clinical Trial Registry: ChiCTR1800014340. Registered on 6 January 2018.
LSD1 inhibition yields functional insulin-producing cells from human embryonic stem cells
Authors: He Fei , Li Ning , Huang Hai-Bo , Wang Jing-Bo , Yang Xiao-Fei , Wang Hua-Dong , Huang Wei , Li Fu-Rong 
Published: April 2020

Abstract
Background
Human embryonic stem cells represent a potentially unlimited source of insulin-producing cells for diabetes therapy. While tremendous progress has been made in directed differentiation of human embryonic stem cells into IPCs in vitro, the mechanisms controlling its differentiation and function are not fully understood. Previous studies revealed that lysine-specific demethylase 1(LSD1) balanced the self-renewal and differentiation in human induced pluripotent stem cells and human embryonic stem cells. This study aims to explore the role of LSD1 in directed differentiation of human embryonic stem cells into insulin-producing cells.

Methods
Human embryonic stem cell line H9 was induced into insulin-producing cells by a four-step differentiation protocol. Lentivirus transfection was applied to knockdown LSD1 expression. Immunofluorescence assay and flow cytometry were utilized to check differentiation efficiency. Western blot was used to examine signaling pathway proteins and differentiation-associated proteins. Insulin/C-peptide release was assayed by ELISA. Statistical analysis between groups was carried out with one-way ANOVA tests or a student’s t test when appropriate.

Results
Inhibition or silencing LSD1 promotes the specification of pancreatic progenitors and finally the commitment of functional insulin-producing β cells; Moreover, inhibition or silencing LSD1 activated ERK signaling and upregulated pancreatic progenitor associated genes, accelerating pre-maturation of pancreatic progenitors, and conferred the NKX6.1+ population with better proliferation ability. IPCs with LSD1 inhibitor tranylcypromine treatment displayed enhanced insulin secretion in response to glucose stimulation.

Conclusions
We identify a novel role of LSD1 inhibition in promoting IPCs differentiation from hESCs, which would be emerged as potential intervention for generation of functional pancreatic β cells to cure diabetes.
Double-strand breaks in lymphocyte DNA of humans exposed to [18F]fluorodeoxyglucose and the static magnetic field in PET/MRI
Authors: Brix Gunnar , Günther Elisabeth , Rössler Ute , Endesfelder David , Kamp Alexandra , Beer Ambros , Eiber Matthias 
Published: April 2020

Abstract
Background
Given the increasing clinical use of PET/MRI, potential risks to patients from simultaneous exposure to ionising radiation and (electro)magnetic fields should be thoroughly investigated as a precaution. With this aim, the genotoxic potential of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and a strong static magnetic field (SMF) were evaluated both in isolation and in combination using the γH2AX assay detecting double-strand breaks in lymphocyte DNA.

Methods
Thirty-two healthy young volunteers allocated to three study arms were exposed to [18F]FDG alone, to a 3-T SMF alone or to both combined over 60 min at a PET/CT or a PET/MRI system. Blood samples taken after in vivo exposure were incubated up to 60 min to extend the irradiation of blood by residual [18F]FDG within the samples and the time to monitor the γH2AX response. Absorbed doses to lymphocytes delivered in vivo and in vitro were estimated individually for each volunteer exposed to [18F]FDG. γH2AX foci were scored automatically by immunofluorescence microscopy.

Results
Absorbed doses to lymphocytes exposed over 60 to 120 min to [18F]FDG varied between 1.5 and 3.3 mGy. In this time interval, the radiotracer caused a significant median relative increase of 28% in the rate of lymphocytes with at least one γH2AX focus relative to the background rate (p = 0.01), but not the SMF alone (p = 0.47). Simultaneous application of both agents did not result in a significant synergistic or antagonistic outcome (p = 0.91).

Conclusion
There is no evidence of a synergism between [18F]FDG and the SMF that may be of relevance for risk assessment of PET/MRI.