bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between thyroid autoimmunity and ovarian reserve in women with hypothyroidism
Authors: Morales-Martínez Felipe A. , Sordia-Hernández Luis H. , Ruiz Martha Merino , Garcia-Luna Selene , Valdés-Martínez Otto H. , Vidal-Gutierez Oscar 
Published: March 2021

Abstract
Background
The ovarian function and therefore the ovarian reserve may be compromised by the pathogenesis of autoimmune diseases of which, Hashimoto’s thyroiditis (HT) is the most common in women of reproductive age. Furthermore, a prolonged reduction in thyroid hormone concentration results in a broad spectrum of reproductive alteration. Previous reports in the literature have been controversial regarding the impact of hypothyroidism and alterations in the ovarian reserve. Thus, this prospective and comparative study aimed to evaluate the association of hypothyroidism with low ovarian reserve.

Materials and Methods
A subset of 27 patients with primary autoimmune hypothyroidism were compared to healthy women. The ovarian reserve was assessed through the anti-Mullerian hormone (AMH) and the antral follicle count (AFC).

Results
Overall, the two groups did not display significant differences in length of their menstrual cycles neither in the AMH serum levels nor the AFC.

Conclusions
No significant alteration was found in the ovarian reserve of women with HT.
Impact of the SARS-COV-2 outbreak on epidemiology and management of major traumain France: a registry-based study (the COVITRAUMA study)
Authors:   and the Traumabase Group, Moyer Jean-Denis , James Arthur , Gakuba Clément , Boutonnet Mathieu , Angles Emeline , Rozenberg Emmanuel , Bardon Jean , Clavier Thomas , Legros Vincent , Werner Marie , Mathais Quentin , Ramonda Véronique , Le Minh Pierre , Berthelot Yann , Colas Clélia , Pottecher Julien , Gauss Tobias 
Published: March 2021

Abstract
Background
Emerging evidence suggests that the reallocation of health care resources during the COVID-19 pandemic negatively impacts health care system. This study describes the epidemiology and the outcome of major trauma patients admitted to centers in France during the first wave of the COVID-19 outbreak.

Methods
This retrospective observational study included all consecutive trauma patients aged 15 years and older admitted into 15 centers contributing to the TraumaBase® registry during the first wave of the SARS-CoV-2 pandemic in France. This COVID-19 trauma cohort was compared to historical cohorts (2017–2019).

Results
Over a 4 years-study period, 5762 patients were admitted between the first week of February and mid-June. This cohort was split between patients admitted during the first 2020 pandemic wave in France (pandemic period, 1314 patients) and those admitted during the corresponding period in the three previous years (2017–2019, 4448 patients). Trauma patient demographics changed substantially during the pandemic especially during the lockdown period, with an observed reduction in both the absolute numbers and proportion exposed to road traffic accidents and subsequently admitted to traumacenters (348 annually 2017–2019 [55.4% of trauma admissions] vs 143 [36.8%] in 2020 p < 0.005). The in-hospital observed mortality and predicted mortality during the pandemic period were not different compared to the non-pandemic years.

Conclusions
During this first wave of COVID-19 in France, and more specifically during lockdown there was a significant reduction of patients admitted to designated trauma centers. Despite the reallocation and reorganization of medical resources this reduction prevented the saturation of the trauma rescue chain and has allowed maintaining a high quality of care for trauma patients.
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing
Authors: Gu Xi , Wang Daqi , Xu Zhijiao , Wang Jinghan , Guo Luo , Chai Renjie , Li Genglin , Shu Yilai , Li Huawei 
Published: March 2021

Abstract
Background
Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection.

Results
The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz.

Conclusions
These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.
Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases
Authors: Yao Chen , Joehanes Roby , Wilson Rory , Tanaka Toshiko , Ferrucci Luigi , Kretschmer Anja , Prokisch Holger , Schramm Katharina , Gieger Christian , Peters Annette , Waldenberger Melanie , Marzi Carola , Herder Christian , Levy Daniel 
Published: March 2021

Abstract
Background
DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases.

Results
We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data.

Conclusions
Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.
Renaissance of armored immune effector cells, CAR-NK cells, brings the higher hope for successful cancer therapy
Authors: Marofi Faroogh , Rahman Heshu Sulaiman , Thangavelu Lakshmi , Dorofeev Aleksey , Bayas-Morejón Favian , Shirafkan Naghmeh , Shomali Navid , Chartrand Max Stanley , Jarahian Mostafa , Vahedi Ghasem , Mohammed Rebar N. , Shahrokh Somayeh , Akbari Morteza , Khiavi Farhad Motavalli 
Published: March 2021

AbstractIn recent decades, a new method of cellular immunotherapy was introduced based on engineering and empowering the immune effector cells. In this type of immunotherapy, the immune effector cells are equipped with chimeric antigen receptor (CAR) to specifically target cancer cells. In much of the trials and experiments, CAR-modified T cell immunotherapy has achieved very promising therapeutic results in the treatment of some types of cancers and infectious diseases. However, there are also some considerable drawbacks in the clinical application of CAR-T cells although much effort is in progress to rectify the issues. In some conditions, CAR-T cells initiate over-activated and strong immune responses, therefore, causing unexpected side-effects such as systemic cytokine toxicity (i.e., cytokine release syndrome), neurotoxicity, on-target, off-tumor toxicity, and graft-versus-host disease (GvHD). To overcome these limitations in CAR-T cell immunotherapy, NK cells as an alternative source of immune effector cells have been utilized for CAR-engineering. Natural killer cells are key players of the innate immune system that can destroy virus-infected cells, tumor cells, or other aberrant cells with their efficient recognizing capability. Compared to T cells, CAR-transduced NK cells (CAR-NK) have several advantages, such as safety in clinical use, non-MHC-restricted recognition of tumor cells, and renewable and easy cell sources for their preparation. In this review, we will discuss the recent preclinical and clinical studies, different sources of NK cells, transduction methods, possible limitations and challenges, and clinical considerations.
The impact of sleep disorders on microvascular complications in patients with type 2 diabetes (SLEEP T2D): the protocol of a cohort study and feasibility randomised control trial
Authors: Antza Christina , Ottridge Ryan , Patel Smitaa , Slinn Gemma , Tearne Sarah , Nicholls Matthew , Cooper Brendan , Ali Asad , Tahrani Abd A. 
Published: March 2021

Abstract
Background
Obstructive sleep apnoea (OSA) is very common in patients with type 2 diabetes (T2D). We and others have shown that OSA was associated with diabetes-related microvascular complications in patients with T2D in cross-sectional and longitudinal studies and that compliance with continuous positive airway pressure (CPAP) reduced the progression of microvascular complications. Hence, we hypothesised that adequate CPAP reduces the development of microvascular complication in patients with T2D.

Methods
SLEEP T2D is a cohort study with embedded feasibility, open-label, parallel-arm, randomised control trial (RCT) over 2 years. The primary aim is the feasibility of conducting a definitive RCT assessing the impact of CPAP on chronic kidney disease and other microvascular complications in patients with T2D. The main parameters are to assess willingness of participants to be randomised, follow-up rates, CPAP adherence/compliance, to optimise the choice of outcome measures for a substantive trial, and to identify the parameters for sample size calculations. The secondary aims of the study are related to the impact of CPAP, sleep-related disorders, and sleep chronotype on a variety of diabetes-related end points. The study participants were recruited from the T2D services in multiple NHS trusts across England. The main exclusion criteria for the cohort study are as follows: T1D, eGFR < 15 mL/min/1.73 m2, known OSA, active malignancy or chronic kidney disease from reasons other than diabetes, pregnancy, professional drivers, and a history of falling asleep whilst driving within last 2 years. The main exclusion criteria from the RCT were as follows: Apnoea-Hypopnoea Index < 10 and Epworth Sleepiness Score ≥ 11. Study participants were extensively phenotyped clinically and biochemically. The OSA diagnosis was based on multichannel portable device (ApneaLink AirTM, Resmed).

Discussion
The feasibility RCT will help us design the future RCT to assess the impact of CPAP on diabetes-related microvascular complications. The cohort study will generate preliminary data regarding the impact of sleep quality, duration, and chronotype on diabetes-related outcomes which could lead to further mechanistic and interventional studies.

Trial registration
ISRCTN, ISRCTN12361838. Registered 04 April 2018, Protocol version: v5.0 02.12.19.
Light a lamp and look at the stock market
Authors: Chundakkadan Radeef 
Published: March 2021

AbstractIn this study, we investigate the impact of the light-a-lamp event that occurred in India during the COVID-19 lockdown. This event happened across the country, and millions of people participated in it. We link this event to the stock market through investor sentiment and misattribution bias. We find a 9% hike in the market return on the post-event day. The effect is heterogeneous in terms of beta, downside risk, volatility, and financial distress. We also find an increase (decrease) in long-term bond yields (price), which together suggests that market participants demanded risky assets in the post-event day.
A guideline for 3D printing terminology in biomedical research utilizing ISO/ASTM standards
Authors: Alexander Amy E. , Wake Nicole , Chepelev Leonid , Brantner Philipp , Ryan Justin , Wang Kenneth C. 
Published: March 2021

AbstractFirst patented in 1986, three-dimensional (3D) printing, also known as additive manufacturing or rapid prototyping, now encompasses a variety of distinct technology types where material is deposited, joined, or solidified layer by layer to create a physical object from a digital file. As 3D printing technologies continue to evolve, and as more manuscripts describing these technologies are published in the medical literature, it is imperative that standardized terminology for 3D printing is utilized. The purpose of this manuscript is to provide recommendations for standardized lexicons for 3D printing technologies described in the medical literature. For all 3D printing methods, standard general ISO/ASTM terms for 3D printing should be utilized. Additional, non-standard terms should be included to facilitate communication and reproducibility when the ISO/ASTM terms are insufficient in describing expository details. By aligning to these guidelines, the use of uniform terms for 3D printing and the associated technologies will lead to improved clarity and reproducibility of published work which will ultimately increase the impact of publications, facilitate quality improvement, and promote the dissemination and adoption of 3D printing in the medical community.
Ultrasonic welding of magnetic hybrid material systems –316L stainless steel to Ni/Cu/Ni-coated Nd2Fe14B magnets
Authors: Liesegang Moritz , Beck Tilmann 
Published: March 2021

AbstractThe performance of electric sensors is continuously improving due to the demands of modern vehicles and electronic devices. Magnetic sensors are used in a wide field of applications. However, handling and mounting the typical high-performance rare earth permanent magnets are challenging due to their brittleness. A constant magnetic flux is a key property of the magnetic setup in many devices. State-of-the-art adhesive bonding of magnets in devices can cause problems due to the low durability and viscous behaviour of adhesive polymers, as the magnet may change its position and hence, the magnetic flux distribution in the magnetic setup changes.Ultrasonic welding is a powerful technique to join hybrid material systems quickly and reliably, providing high joint strength, even for brittle materials such as glasses, ceramics and rare earth permanent magnets. The latter is being investigated in this work for the first time. The ultrasonic welding process was adapted to join 316L stainless steel, representing potential components of magnetic devices, to Ni/Cu/Ni-coated Nd2Fe14B. In addition to directly joined steel/magnet-hybrids, ductile aluminium and nickel interlayers were used in order to enhance the joint strength.Process parameters were developed and evaluated considering the resulting shear strength of the joints. The highest shear strength of 35 MPa was achieved for 316L/Nd2Fe14B and 316L/Al/Nd2Fe14B, which is more than twice the shear strength of adhesively bonded joints of up to 20 MPa, according to the literature. The functional performance of the hybrid material systems, evaluated by the magnetic flux density of the hybrid material systems was the highest for directly bonded joints, and those with a nickel interlayer, which did not show any losses in comparison to the single magnet in its initial state. Joints with an aluminium interlayer showed losses of 3% and adhesively bonded joints showed losses of 7% of the magnetic flux density.In summary, the results of this work indicate that ultrasonic welding is a suitable technique to improve the production process and performance of magnetic devices.
Tipifarnib in Head and Neck Squamous Cell Carcinoma WithHRASMutations
Authors: Ho Alan L. , Brana Irene , Haddad Robert , Bauman Jessica , Bible Keith , Oosting Sjoukje , Wong Deborah J. , Ahn Myung-Ju , Boni Valentina , Even Caroline , Fayette Jerome , Flor Maria José , Harrington Kevin , Hong David S. , Kim Sung-Bae , Licitra Lisa , Nixon Ioanna , Saba Nabil F. , Hackenberg Stephan , Specenier Pol , Worden Francis , Balsara Binaifer , Leoni Mollie , Martell Bridget , Scholz Catherine , Gualberto Antonio 
Published: March 2021

PURPOSEMutations in the HRAS (m HRAS) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M m HRAS HNSCC.METHODSWe enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m HRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m HRAS variant allele frequency (VAF) data, enrollment was limited to those with a m HRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles.RESULTSOf the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%).CONCLUSIONTipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist ( NCT02383927 ).
Extended UV detection bandwidth: h-BN/Al powder nanocomposites photodetectors sensitive in a middle UV region due to localized surface plasmon resonance effect
Authors: Volkov Ilia N. , Yermekova Zhanna S. , Khabibrakhmanov Almaz I. , Kovalskii Andrey M. , Corthey Shakty , Tameev Alexey R. , Aleksandrov Alexey E. , Sorokin Pavel B. , Shtansky Dmitry V. , Matveev Andrei T. 
Published: March 2021

AbstractThe development of high-effective photodetectors operating in a wide spectral range is an important technological task. In this work we have demonstrated that the detection bandwidth ofh-BN photodetectors in the UV range can be extended due to the surface plasmon resonance (SPR) effect. Theoretical calculations showed that, among Al, Au, Ag, and Cu, Al is the most suitable metal for theh-BN UV sensible detectors due to the SPR effect in the middle UV range. Based on the theoretical predictions, a simple and highly efficient method for obtainingh-BN/Al nanocomposites for localized SPR-based UV detectors was developed. It was demonstrated that theh-BN/Al material is sensitive to UV radiation with a wavelength of 266 nm that is far away of the detection limit of 240 nm inherent for pureh-BN.
Management of psychotropic medications in adults with intellectual disability: a scoping review protocol
Authors: Costello Ashley , Hehir Cian , Sharma Drona , Doody Owen , Kelly Dervla 
Published: March 2021

Introduction: Psychotropic medications are commonly prescribed among adults with intellectual disability (ID), often in the absence of a psychiatric diagnosis. As such, there is great disparity between the estimated prevalence of mental illness and the rates of psychotropic medication use amongst people with ID. ‘Off-label’ use of these medications may account for much of this discrepancy, in particular their use in the management of challenging behaviour. This has come under scrutiny due to the myriad of side effects and the deficiency of high-quality data supporting their use for this indication. Understanding the causes and justifications for such disparity is essential in discerning the efficacy of current prescription practice. Objective: To explore the existing evidence base regarding the prescription and management of psychotropic medications in adults with ID. The aim will be achieved through identifying the psychotropic medications commonly prescribed, the underlying rationale(s) for their prescription and the evidence available that demonstrates their appropriateness and effectiveness. Additionally, the paper will seek to evaluate the availability of any existing guidance that informs the management of these medications, and the evidence and outcomes of psychotropic medication dose reduction and/or cessation interventions. Inclusion criteria: This review will consider studies that focus on the use of psychotropic medications amongst patients with ID. Methods: Research studies (qualitative, quantitative and mixed design) and Grey Literature (English) will be included. The search will be conducted without time restrictions. Databases will include: Ovid MEDLINE, Embase, CINAHL, JBI Evidence Synthesis, Cochrane Central Register of Controlled Trials, Cochrane Databased of Systematic Reviews, PsycINFO and Scopus. A three-step search strategy will be followed, with results screened by two independent reviewers. Data will be extracted independently by two reviewers using a data extraction tool with results mapped and presented using a narrative form supported by tables and diagrams.