bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-genome mate-pair sequencing of apparently balanced chromosome rearrangements reveals complex structural variations: two case studies
Authors: Tan Yaqi , Cheng Dehua , Tan Yue-Qiu 
Published: February 2020

Abstract
BACKGROUND: Apparently balanced chromosome rearrangements (ABCRs) in non-affected individuals are well-known to have high reproductive risks such as infertility, abnormal offspring, and pregnancy loss. However, caution should be exercised in genetic counseling and reproductive intervention because cryptic unbalanced defects and genome structural variations beyond the resolution of routine cytogenetics may get omitted.CASE PRESENTATION: Two cases of ABCRs were recruited in this study. In family 1, the couple suffered two terminated pregnancies and underwent labor induction. Single nucleotide polymorphism (SNP) array analysis of the aborted sample from the second pregnancy showed a 10.8 Mb heterozygous deletion at 10q26.13q26.3 and a 5.5 Mb duplication at 19q13.41-q13.43. The non-affected father was diagnosed as a carrier of three-way complex chromosomal rearrangement [t(6;10;19)(p22;q26;q13)] by karyotyping. Whole-genome mate-pair sequencing revealed a cryptic breakpoint on derivative (der) chromosome 19 indicating that the karyotype was a more complex structural rearrangement including four breakpoints. Three genes, FAM24B, CACNG8, and KIAA0556, were disrupted without causing any abnormal phenotype in the carrier. In family 2, the couple suffered from a spontaneous miscarriage. They had an affected child with multiple congenital malformations and an unbalanced karyotype, 46,XY,der(11)t(6;11)(q13;p11.2). The female partner was considered a balanced translocation carrier with the karyotype 46,XX,t(6;11)(q13;p11.2)dn. Further SNP array and fluorescent in situ hybridization (FISH) indicated a cryptic insertion between chromosome 6 and chromosome 11. Finally, whole-genome mate-pair sequencing revealed an extremely complex genomic structural variation, including a cryptic deletion and 12 breakpoints on derivative chromosome 11[der(11)], and 1 breakpoint on derivative chromosome 6 [der(6)].CONCLUSIONS: Our study investigated two rare cases of ABCRs and demonstrated that whole-genome mate-pair sequencing is a powerful approach to analyze the genome complex structural variation. In case of ABCRs detected by conventional cytogenetic techniques, whole genome sequencing (WGS) based approaches should be considered for accurate diagnosis, effective genetic counseling, and correct reproductive intervention to avoid recurrence risks.
The Role of NMDA receptors in rat propofol self-administration
Authors: Chen Bei ping , Huang Xi-xi , Dong Dong-mei , Wu Hui , Zhu Tian-qi , WANG Ben-fu 
Published: February 2020

Abstract
Aim

Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration.

Methods

Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01).

Conclusion

These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.
Sahaj Samadhi Meditation versus a Health Enhancement Program for depression in chronic pain: protocol for a Randomized Controlled Trial and Implementation Evaluation
Authors: Sud Abhimanyu , Nelson Michelle L. A. , Cheng Darren K. , Armas Alana , Foat Kirk , Greiver Michelle , Hosseiny Fardous , Katz Joel , Moineddin Rahim , Mulsant Benoit H. , Newman Ronnie I. , Rivlin Leon , Vasudev Akshya , Upshur Ross 
Published: February 2020

Abstract
Background: Despite the high prevalence of comorbid chronic pain and depression, this comorbidity remains understudied. Meditation has demonstrated efficacy for both chronic pain and depression independently, yet there have been few studies examining its effectiveness when both conditions are present concurrently. Furthermore, while meditation is generally accepted as a safe and effective health intervention, little is known about how to implement meditation programs within or alongside the healthcare system. Methods: We will conduct a hybrid type 1 effectiveness-implementation evaluation. To measure effectiveness, we will conduct a randomized controlled trial (RCT) comparing Sahaj Samadhi Meditation (SSM) versus the Health Enhancement Program (HEP) in 160 people living with chronic pain, clinically significant depressive symptoms, and on long-term opioid therapy. Changes in depressive symptoms will be our primary outcome; pain severity, pain related function, opioid use, and quality of life will be the secondary outcomes. The primary endpoint will be at 12 weeks with a secondary endpoint at 24 weeks to measure sustainability of acute effects. Patients will be recruited from a community-based chronic pain clinic in a large urban centre in Mississauga, Canada. The meditation program will be delivered in the clinical environment where patients normally receive their chronic pain care by certified meditation teachers who are not regulated healthcare providers. We will use a mixed-methods design using the multi-level framework to understand the implementation of this particular co-location model. Discussion: Results of this hybrid evaluation will add important knowledge about the effectiveness of meditation for managing depressive symptoms in people with chronic pain. The implementation evaluation will inform both effectiveness outcomes and future program development, scalability, and sustainability.
Effectiveness and Tolerability of Repetitive Transcranial Magnetic Stimulation for Preventive Treatment of Episodic Migraine: A Single Centre, Randomised, Double-Blind, Sham-Controlled Phase 2 Trial (Magnet-EM).
Authors: Safiai Nabil Izzaatie Mohamad , Amir Nur Ain , Basri Hamidon bin , Mat Liyana Najwa Inche , Hoo Fan Kee , Khan Abdul Hanif Khan Yusof , Loh Wei Chao , Chia Peck Kee , Ramachandran Vasudevan , Din Hazwan Mat , Samsudin Intan Nureslyna , Fernandez Aaron , Mohamed Mohd Hazmi , Ching Siew Mooi , Hashim Hasnur Zaman , Sulaiman Wan Aliaa Wan 
Published: February 2020

Abstract
Background This is a phase II randomised, double-blind, placebo-controlled trial to evaluate the effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine among migraine subjects. Methods Subjects age 18 to 60 years will undergo a baseline evaluation to ascertain the diagnosis of migraine based on International Classification of Headache Disorder 3 rd Edition (ICHD-3). Only those who fulfil the ICHD-3 criteria for episodic migraine and compliant to the headache diary during a month run-in period will be enrolled. A total of 76 subjects will be randomised to receive either transcranial magnetic stimulation or placebo for 5 sessions within 2 weeks duration. Follow up sessions will be conducted monthly for three consecutive months. Prior to treatment, subjects will be required to fill up questionnaires and undergo few procedures such as electroencephalography, transcranial doppler ultrasound and biochemical analysis for serum serotonin, serum calcitonin-gene related peptide and serum beta-endorphin. These procedures will be repeated post-treatment during their last visit. The primary outcome measure of this study is the difference in mean monthly migraine days at baseline and at month 1, 2 and 3 after treatment sessions. Discussion Following evidence from previous studies showing restoration of dorsolateral prefrontal cortex (DLPFC) activation to near normal level, the rTMS intervention will target left DLPFC in this study. Meanwhile, in terms of treatment frequency, the least number of sessions reported which proved to be effective in treating migraine was three session of rTMS given in alternate days. Hence, for this study, an intermediate duration of treatment sessions is selected. It is set to five treatment sessions given within 2 weeks duration.
Evaluating hearing performance with cochlear implants within the same patient using daily randomization and imaging based fitting - The ELEPHANT study
Authors: Lambriks Lars , Hoof Marc Van , Debruyne Joke , Janssen Miranda , Chalupper Josef , Heijden Kiki Van der , Hof Janny , Hellingman Katja , George Erwin , Devocht Elke 
Published: February 2020

Abstract
Background : Prospective research in the field of cochlear implants is hampered by methodological issues and small sample sizes. The ELEPHANT study presents an alternative clinical trial design with a daily randomized approach evaluating individualized tonotopical CI fitting. Methods : A single blinded, daily randomized clinical trial will be implemented to evaluate a new imaging based CI mapping strategy. A minimum of 20 participants will be included from the start of the rehabilitation process with a 1-year follow-up period. Based on a post-operative cone beam CT scan (CBCT), mapping of electrical input will be aligned to natural place-pitch arrangement in the individual cochlea. Adjustments to the CI’s frequency allocation table will be made so electrical stimulation of frequencies will match as closely as possible with corresponding acoustic locations in the cochlea. A randomization scheme will be implemented whereby the blinded subject crosses over between the experimental and standard fitting program on a daily basis, and thus effectively acts as his own control, followed by a period of free choice between both maps to incorporate patient preference. With this new approach the occurrence of a first-order carryover effect and a limited sample size is addressed. Discussion : The experimental fitting strategy is thought to give rise to a steeper learning curve, result in a better performance in challenging listening situations, improve sound quality, complement better with residual acoustic hearing in the contralateral ear and win the preference of CI-recipients. Concurrently, the suitability of the novel trial design will be considered in investigating these hypotheses. Trial registration : ClinicalTrials.gov: NCT03892941, registered 27 March 2019, https://clinicaltrials.gov/ct2/show/NCT03892941
Understanding access to professional healthcare among asylum seekers facing gender-based violence: a qualitative study from a stakeholder perspective
Authors: Sapia Mirjam Rodella , Wangmo Tenzin , Dagron Stéphanie , Elger Bernice S. 
Published: February 2020

Abstract
Background: When it comes to gender-based violence (GBV), migrant women and girls represent the most vulnerable group. GBV can happen at any stage of migrants’ flight and/or during asylum process. It has severe consequences on their life and health. Victims therefore need timely access to healthcare. This study explores the context GBV victims are faced with when they seek refuge in Switzerland. The study focuses on the organizational framework and the current strategies handling medical and psychological support. It identifies access barriers and maps needed support within the health system. Methods : Qualitative methodology was used where we conducted five semi-structured focus groups and three interviews with sixteen stakeholders involved in the asylum process and health care professionals. We analysed the data using framework analysis. Results : Study participants noted lack of confidence from the GBV victims in the legal and in the healthcare system as major barriers to disclosure of GBV. Since only GBV exerted before fleeing the home country gives the right to asylum, they also pointed out that victims do not disclose GBV that took place after they left their home country. Language was identified as a barrier to disclosure as well as healthcare access. Continuity of care at the moment of transfer from federal to cantonal accommodations is another issue that was deemed critical. Study participants felt that health professionals must be trained to identify GBV victims. First-contact caregivers available to these victims were deemed as the most competent professionals that could act as a “GBV coordinator”. Conclusion : In Switzerland, access to healthcare is guaranteed to all asylum seekers on a legal and structural level. Yet, health seeking by GBV survivors is hindered by major factors such as (lack of) confidence in the legal system, trust building in health providers and a breach in continuity of care during the asylum process. Trust building in legal institutions, health structures and professionals should be enhanced to facilitate disclosure and strengthen resilience. This includes a healthcare system with competent professional, support with language, cultural needs and seamless continuity of care beyond cantonal borders.
An overlooked cause of longitudinally extensive spinal cord lesions: Primary central nervous system lymphoma
Authors: Wang Meng , Qi Baochang , Han Jinming , Guo Chunjie , Qu Limei , Zhu Jie , jin tao 
Published: February 2020

Abstract
Background: Primary central nervous system lymphoma (PCNSL ) is a rare and aggressive malignant tumor. It is easy to be misdiagnosed due to its low incidence and unspecific presentations in clinical practice. PCNSL mainly occurs intracranially in the brain while spinal cord is rarely involved. Case presentation: Here we report a 76-year-old woman who had a suspicious tumor history and presented retardant paralysis, bladder dysfunction and sensory loss of the lower limbs. Magnetic resonance imaging (MRI) of the thoracic spine disclosed longitudinally extensive lesions extending from thoracic 4 (T4) to lumbar 1 (L1) vertebral level with an enhanced nodular lesion noting at levels of T10 and T11 . In order to further identify the cause, the whole body 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) was performed and showed a hypermetabolic nodule corresponded to MRI enhancing lesions, which further suggesting the possibility of a tumor. The patient then underwent a surgical resection and spinal cord biopsy confirmed the diagnosis of non-Hodgkin's lymphoma (diffuse large B-cell type). The patient then received a high-dose chemotherapy based on methotrexate combined with Rituximab. Unfortunately, the symptoms of this patient have not been improved significantly after three rounds of chemotherapy. Conclusion: Our case indicates that PCNSL may also serve as a possible cause for longitudinally extensive spinal cord lesions, especially the patients who had a suspicious tumor history, MRI enhancing lesion s in the spinal cord corresponded to hypermetabolic nodules on 18 F-FDG- PET/CT at the same level.
Accommodating conscientious objection in the midwifery workforce: a ratio-data analysis of midwives, birth and late abortions in 18 European countries in 2016
Authors: Fleming Valerie , Maxwell Clare , Ramsayer Beate 
Published: February 2020

Abstract
Background In recent years the role of a midwife has expanded to include the provision of abortion related care. The laws on abortion in many European countries allow for those who hold a conscientious objection to participating to refrain from such participation. However, some writers have expressed concerns that this may have a detrimental effect on the workforce and limit women’s access to the service. Method The aim of this study was to provide a picture of the potential exposure midwives in Europe have to late abortions, an important factor in the integration of accommodation of conscientious objection to abortion by midwives into workload planning. We collected data from Ministries of Health or government statistical departments in 32 European countries on numbers of: births, abortions, late abortions and midwives in 2016. We conducted a ratio-data analysis in those countries that met the inclusion criteria. Results 18 of the 32 countries provided full data thus our calculations are based on a total of 4,036,633 live births, 49,834 late abortions and a total of 132,071 midwives. The calculated ratios of live births to midwife, abortions to midwife and late abortions to midwife illustrate the wide variations between countries in relation to ratios of midwives to live births (15.22 - 53.99) and late abortions, (0.17-1.47) Conclusions This study provides the first comprehensive insight to ratios relating to birth and abortion, especially late abortion services, with regard to the midwifery workforce. It is essential to improve the reporting of abortion data and access to it within Europe to support evidence-informed decisions on optimising the contribution of the midwifery workforce especially within highly contentious fields such as abortion services. However, given our findings, we believe that there should be neither be any difficulty for those who are responsible for workload allocation nor compromises to a women’s right to abortion services.
Cervical and oropharyngeal human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil
Authors: Suehiro Tamy Taianne , Damke Gabrielle Marconi Zago Ferreira , Damke Edilson , Ramos Paloma Luana Rodrigues de Azevedo , Silva Marcela de Andrade Pereira , Pelloso Sandra Marisa , Huh Warner K , Franco Ricardo Argemiro Fonseca , Silva Vânia Ramos Sela da , Scarinci Isabel Cristina , Consolaro Marcia Edilaine Lopes 
Published: February 2020

Abstract
Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects concerning the interrelationship between HPV infections in both body sites remain unknown, specifically in human immunodeficiency virus (HIV)-positive (HIV+) female patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oropharyngeal HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil. Material and methods: Cervical and endocervical samples for cytological screening and HPV detection and oropharyngeal samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. Detection and typing of HPV were performed using the Kit Multiplex XGEN Multi HPV Chip HS12. Results: HIV infection was well controlled in this cohort, but women who exhibited 1–100.000 viral copies/mL were significantly associated with HPV-positive status (P = 0.03). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oropharyngeal HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oropharyngeal HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oropharyngeal infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women, however HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented types less common, mainly in oropharyngeal mucosa. Conclusion: Our data support the importance of HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women.
Successful pregnancy after complete resection of leiomyomatosis peritonealis disseminate without recurrence: A case report with next generation sequencing analysis and literature review
Authors: Bu Hualei , Jin Chengjuan , Fang Yan , Ma Yana , Wang Xiao , Chen Jingying , Chen Lijun 
Published: February 2020

Abstract
Background: Peritoneal leiomyomatosis disseminate (LPD) is a rare disease characterized by widespread dissemination of leiomyomas nodules throughout the peritoneal and omental surfaces. Reports of pregnancy with LPD are even rarer. Therefore, there is no clear consensus on the treatment of LPD on pregnancy, and the pathogenesis is still unclear. Case presentation：We reported a case of LPD patient who developed during pregnancy. The patient underwent cesarean section at 32 weeks of gestation while removing all visible tumors, and no LPD lesions were seen in the subsequently cesarean section at full-term. NGS of LPD lesions detected 4 mutations with focal high-level amplifications of CDK4 (Cyclin-dependent kinases 4), NBN (Nibrin), DAXX (Death domain associated protein) and MYC (Myelocytomatosis oncogene). Immunohistochemistry staining analysis among benign leiomyoma, LPD and leiomyosarcoma verified that LPD was an unusual intermediate between benign and malignant uterine smooth muscle tumors. Besides, LPD is a hormonal-dependent leiomyoma. After detailed literature search, we summarized the detailed clinical features and follow-up information of patients with LPD during pregnancy. Conclusions: This is the first reported LPD case of successful term pregnancy without recurrence, following resection of all visible lesions in prior pregnancy. LPD is an unusual intermediate between benign and malignant uterine smooth muscle tumors.
Systemic cytokine potential in patients with chronic obstructive pulmonary disease who completed treatment for pulmonary tuberculosis
Authors: Khrenov A. A. , Fedoseeva V. M. , Grishin M. M. 
Published: February 2020

The objective: to investigate the cytokine potential (TGF-β1, TNF-α, IL-1β, IL-4) in the systemic blood circulation of patients who successfully completed treatment for pulmonary tuberculosis, depending on whether they have chronic obstructive lung disease (COPD).Subjects and methods. The study included 118 patients who had successfully completed treatment for pulmonary tuberculosis by the time of the examination. Group 1 included 79 patients with different forms of pulmonary tuberculosis without COPD, Group 2 – 39 patients with different forms of pulmonary tuberculosis and concurrent COPD. The Control Group consisted of 24 healthy individuals.In all patients, the levels of IL-1β, TNF-α and IL-4, as well as the active form of TGF-β1 were tested in the systemic blood circulation using commercial ELISA test systems.Results. By the time of successful tuberculosis treatment completion, COPD patients were found to develop the following: a special Th2-associated form of immune imbalance characterized by the reduced systemic level of TNF-α in combination with the increased level of IL-4; the increased risk of development and progression of pulmonary fibrosis due to the high level of growth factor TGF-β1 (in comparison with patients without COPD); elevated levels of TGF-β1 (compared with patients without COPD), creating favorable endogenous conditions for tuberculosis relapse.