bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel LAMA2 c.2217G > A, p.(Trp739*) mutation in a Moroccan patient with congenital muscular dystrophy: a case report
Authors: El Kadiri Youssef , Ratbi Ilham , Laarabi Fatima Zahra , Kriouile Yamna , Sefiani Abdelaziz , Lyahyai Jaber 
Published: April 2021

Abstract
Background
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a rare autosomal recessive genetic condition caused by deleterious mutations in the LAMA2 gene encoding the laminin-α2 chain. It is the most frequent subtype of congenital muscular dystrophies (CMDs) characterized by total laminin-α2 deficiency with muscle weakness at birth or in the first six months of life. To the best of our knowledge, this study reports the first molecular diagnosis and genetic defect of this heterogeneous form of CMD performed in a Moroccan medical genetic center using next-generation sequencing (NGS). It allows us to expand the mutational spectrum of the LAMA2 gene.

Case presentation
We report the case of a female Moroccan child with clinical and paraclinical features in favor of a CMD. She has global congenital hypotonia with generalized muscle weakness, psychomotor retardation, increased serum creatine kinase, and normal brain scan at the age of six months. Targeted NGS leads to the identification of a novel homozygous nonsense mutation c.2217G > A, p.(Trp739*) in the exon 16 of LAMA2. Sanger sequencing confirmed this mutation in the affected patient and showed that her parents are heterozygous carriers.

Conclusions
A modern genetic analysis by NGS improves the genetic diagnosis pathway for adequate genetic counseling of affected families more precisely. An accession number from the National Center for Biotechnology Information (NCBI) ClinVar database was retrieved for this novel LAMA2 mutation.
Small-volume detection: platform developments for clinically-relevant applications
Authors: Sung Wei-Hsuan , Tsao Yu-Ting , Shen Ching-Ju , Tsai Chia-Ying , Cheng Chao-Min 
Published: April 2021

AbstractBiochemical analysis of human body fluids is a frequent and fruitful strategy for disease diagnosis. Point-of-care (POC) diagnostics offers the tantalizing possibility of providing rapid diagnostic results in non-laboratory settings. Successful diagnostic testing using body fluids has been reported on in the literature; however, small-volume detection devices, which offer remarkable advantages such as portability, inexpensiveness, capacity for mass production, and tiny sample volume requirements have not been thoroughly discussed. Here, we review progress in this research field, with a focus on developments since 2015. In this review article, we provide a summary of articles that have detailed the development of small-volume detection strategies using clinical samples over the course of the last 5 years. Topics covered include small-volume detection strategies in ophthalmology, dermatology or plastic surgery, otolaryngology, and cerebrospinal fluid analysis. In ophthalmology, advances in technology could be applied to examine tear or anterior chamber (AC) fluid for glucose, lactoferrin, interferon, or VEGF. These approaches could impact detection and care for diseases including diabetic mellitus, dry-eye disease, and age-related maculopathy. Early detection and easy monitoring are critical approaches for improving overall care and outcome. In dermatology or plastic surgery, small-volume detection strategies have been applied for passive or interactive wound dressing, wound healing monitoring, and blister fluid analysis for autoimmune disease diagnosis. In otolaryngology, the analysis of nasal secretions and mucosa could be used to differentiate between allergic responses and infectious diseases. Cerebrospinal fluid analysis could be applied in neurodegenerative diseases, central neural system infection and tumor diagnosis. Other small-volume fluids that have been analyzed for diagnostic and monitoring purposes include semen and cervico-vaginal fluids. We include more details regarding each of these fluids, associated collection and detection devices, and approaches in our review.
Regulatory standards and processes for over-the-counter availability of hormonal contraception and drugs for medical abortion in five countries in the Eastern Mediterranean Region
Authors: Ammerdorffer Anne , Laws Mark , Awiligwe Arinze , Erb Florence , Im-Amornphong Wallada , Gülmezoglu A. Metin , Chinery Lester , Lucido Briana , Narasimhan Manjulaa 
Published: April 2021

AbstractThe World Health Organization 2019 WHO consolidated guideline on self-care interventions for health: sexual and reproductive health and rights includes recommendations on self-administration of injectable contraception, over-the-counter (OTC) oral contraception and self-management of medical abortion. A review of the regulatory status of these two self-care interventions can highlight processes required to ensure that the quality of the medicines and safety of individuals are safeguarded in the introduction and scale-up in countries. This review outlines the legal regulatory status of prescription-only medicine (POM) and OTC contraceptives, including emergency contraception, and drugs for medical abortion in Egypt, Jordan, Lebanon, Morocco and Tunisia using information obtained from internet searches, regulatory information databases and personal contacts. In addition, the review examines whether the national medicines regulatory authorities have documented procedures available to allow for a change in status from a POM to OTC to allow for increased accessibility, availability and uptake of self-care interventions recommended by WHO. Egypt, Jordan and Lebanon have a documented national OTC list available. The only contraceptive product mentioned in the OTC lists across all five countries is ellaOne (ulipristal acetate for emergency contraception), which is publicly registered in Lebanon. None of the five countries has an official documented procedure to apply for the change of POM to OTC. Informal procedures exist, such as the ability to apply to the national medicines regulatory authority for OTC status if the product has OTC status in the original country of manufacture. However, many of these procedures are not officially documented, highlighting the need for establishing sound, affordable and effective regulation of medical products as an important part of health system strengthening. From a public health perspective, it would be advantageous for licensed products to be available OTC. This is particularly the case for settings where the health system is under-resourced or over-stretched due to health emergencies. Readiness of national regulatory guidelines and OTC procedures could lead to increased access, availability and usage of essential self-care interventions for sexual and reproductive health and rights.
Community-led HIV self-testing for men who have sex with men in Lebanon: lessons learned and impact of COVID-19
Authors: Maatouk Ismael , Nakib Mostafa El , Assi Moubadda , Farah Patrick , Makso Bertho , Nakib Clara El , Rady Alissar 
Published: April 2021

Abstract
Background
In Lebanon, HIV is concentrated in both native and refugee communities of men who have sex with men (MSM). For over 10 years, the National AIDS Program (NAP) has offered HIV voluntary counselling and testing through a partnership with nongovernmental organizations (NGOs). In 2018, implementation of HIV self-tests (HIVST) was introduced, and this self-care intervention has been further scaled up during the coronavirus disease 2019 (COVID-19) pandemic. This paper (1) describes the effectiveness of implementing HIVST in Lebanon, and (2) discusses how the success of HIVST implementation has been reflected during the COVID-19 pandemic.

Methods
The NAP conducted a series of workshops (July–November 2018) to introduce HIVST services for healthcare workers working at different NGOs. The workshops highlighted that HIVST would be distributed for free, that it would be confidential and voluntary, and that participants were encouraged to notify the NGOs of their results, which would be kept strictly confidential. NGOs collected data anonymously and confidentially from beneficiaries (age, consistency of condom use and HIV testing history), who were asked to call back with the results of their HIVST. At the NAP, data were combined, aggregated and analysed.

Results
In 2019, the NGOs distributed 1103/1380 (79.9%) HIVST kits to their beneficiaries. The NGOs collected feedback on 111 kit results, of which two were HIV-positive. Feedback about HIVST results from beneficiaries was low (111/1103) due to noncompliance of beneficiaries and the lack of human and financial resources in the NGOs. From January through May 2020, a total of 625/780 HIVST kits (80.1%) were distributed. This period was divided into pre-COVID-19 and during COVID-19. The follow-up with the beneficiaries during COVID-19 was much improved because of the absence of on-site activities, shifting more efforts towards HIVST (449/625). There have been no reports of social harm related to HIVST.

Conclusion
HIVST implementation in Lebanon serves as an example of introducing a self-care intervention as part of a community-led effort. In order to maintain HIVST services at the same improved level, reorganization of care is needed within each NGO following the adaptation process due to COVID-19, along with continuous monitoring and evaluation of HIVST reported data.
Protein phosphatases in TLR signaling
Authors: Seumen Clovis H. T. , Grimm Tanja M. , Hauck Christof R. 
Published: April 2021

AbstractToll-like receptors (TLRs) are critical sensors for the detection of potentially harmful microbes. They are instrumental in initiating innate and adaptive immune responses against pathogenic organisms. However, exaggerated activation of TLR receptor signaling can also be responsible for the onset of autoimmune and inflammatory diseases. While positive regulators of TLR signaling, such as protein serine/threonine kinases, have been studied intensively, only little is known about phosphatases, which counterbalance and limit TLR signaling. In this review, we summarize protein phosphorylation events and their roles in the TLR pathway and highlight the involvement of protein phosphatases as negative regulators at specific steps along the TLR-initiated signaling cascade. Then, we focus on individual phosphatase families, specify the function of individual enzymes in TLR signaling in more detail and give perspectives for future research. A better understanding of phosphatase-mediated regulation of TLR signaling could provide novel access points to mitigate excessive immune activation and to modulate innate immune signaling.
Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Authors: Wirth Klaus J. , Scheibenbogen Carmen 
Published: April 2021

AbstractChronic Fatigue Syndrome or Myalgic Encephaloymelitis (ME/CFS) is a frequent debilitating disease with an enigmatic etiology. The finding of autoantibodies against ß2-adrenergic receptors (ß2AdR) prompted us to hypothesize that ß2AdR dysfunction is of critical importance in the pathophysiology of ME/CFS. Our hypothesis published previously considers ME/CFS as a disease caused by a dysfunctional autonomic nervous system (ANS) system: sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles, which in the latter is opposed by the metabolically stimulated release of endogenous vasodilators (functional sympatholysis). An enigmatic bioenergetic disturbance in skeletal muscle strongly contributes to this release. Excessive generation of these vasodilators with algesic properties and spillover into the systemic circulation could explain hypovolemia, suppression of renin (paradoxon) and the enigmatic symptoms. In this hypothesis paper the mechanisms underlying the energetic disturbance in muscles will be explained and merged with the first hypothesis. The key information is that ß2AdR also stimulates the Na+/K+-ATPase in skeletal muscles. Appropriate muscular perfusion as well as function of the Na+/K+-ATPase determine muscle fatigability. We presume that dysfunction of the ß2AdR also leads to an insufficient stimulation of the Na+/K+-ATPase causing sodium overload which reverses the transport direction of the sodium-calcium exchanger (NCX) to import calcium instead of exporting it as is also known from the ischemia–reperfusion paradigm. The ensuing calcium overload affects the mitochondria, cytoplasmatic metabolism and the endothelium which further worsens the energetic situation (vicious circle) to explain postexertional malaise, exercise intolerance and chronification. Reduced Na+/K+-ATPase activity is not the only cause for cellular sodium loading. In poor energetic situations increased proton production raises intracellular sodium via sodium-proton-exchanger subtype-1 (NHE1), the most important proton-extruder in skeletal muscle. Finally, sodium overload is due to diminished sodium outward transport and enhanced cellular sodium loading. As soon as this disturbance would have occurred in a severe manner the threshold for re-induction would be strongly lowered, mainly due to an upregulated NHE1, so that it could repeat at low levels of exercise, even by activities of everyday life, re-inducing mitochondrial, metabolic and vascular dysfunction to perpetuate the disease.
Utilization of wearable technology to assess gait and mobility post-stroke: a systematic review
Authors: Peters Denise M. , O’Brien Emma S. , Kamrud Kira E. , Roberts Shawn M. , Rooney Talia A. , Thibodeau Kristen P. , Balakrishnan Swapna , Gell Nancy , Mohapatra Sambit 
Published: April 2021

Abstract
Background
Extremity weakness, fatigue, and postural instability often contribute to mobility deficits in persons after stroke. Wearable technologies are increasingly being utilized to track many health-related parameters across different patient populations. The purpose of this systematic review was to identify how wearable technologies have been used over the past decade to assess gait and mobility in persons with stroke.

Methods
We performed a systematic search of Ovid MEDLINE, CINAHL, and Cochrane databases using select keywords. We identified a total of 354 articles, and 13 met inclusion/exclusion criteria. Included studies were quality assessed and data extracted included participant demographics, type of wearable technology utilized, gait parameters assessed, and reliability and validity metrics.

Results
The majority of studies were performed in either hospital-based or inpatient settings. Accelerometers, activity monitors, and pressure sensors were the most commonly used wearable technologies to assess gait and mobility post-stroke. Among these devices, spatiotemporal parameters of gait that were most widely assessed were gait speed and cadence, and the most common mobility measures included step count and duration of activity. Only 4 studies reported on wearable technology validity and reliability metrics, with mixed results.

Conclusion
The use of various wearable technologies has enabled researchers and clinicians to monitor patients’ activity in a multitude of settings post-stroke. Using data from wearables may provide clinicians with insights into their patients’ lived-experiences and enrich their evaluations and plans of care. However, more studies are needed to examine the impact of stroke on community mobility and to improve the accuracy of these devices for gait and mobility assessments amongst persons with altered gait post-stroke.
Sex differences in association between cognitive impairment and clinical correlates in Chinese patients with first-episode drug-naïve schizophrenia
Authors: Zhao Na , Wang Xiao Hong , Kang Chuan Yi , Zheng Yue , Yang Li Ying , Guan Tie Feng , Bai Yun Xia , Wei Ran , Hinman Hunter C. , Zhang Xiang Yang 
Published: April 2021

Abstract
Background
Schizophrenia is a complex mental illness with significant sex differences. Cognitive impairment is common in patients with schizophrenia, even in remission. This study was designed to examine the sex differences in the relationship between cognitive impairment and clinical correlations with first-episode drug-naïve (FEDN) schizophrenia.

Methods
93 FEDN patients (male/female = 45/48) and 160 controls (male/female = 74/86) were enrolled to compare the sex differences in cognitive functions measured by the MATRICS Consensus Cognitive Battery (MCCB). Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Scale (HAMD) were used to evaluate patients' clinical symptoms. We compared cognitive impairment with sociodemographic characteristics and measures of different genders, as well as group-by-sex interactions.

Results
Our results showed that male patients had significantly lower scores for symbol coding, digital sequence, and verbal learning than female patients, while the healthy controls showed similar sex differences. In female patients, multiple linear regression analysis confirmed that PANSS negative symptoms and general psychopathology scores, HAMD total score, and education level were independent contributors to MCCB total score. In male patients, only education was an independent contributor to MCCB total score.

Conclusions
These findings revealed significant sex differences in cognitive impairments and clinical symptoms in FEDN, which will be worthy of a follow-up study of schizophrenia in the future.
Development and validation of a nomogram predicting the risk of recurrent lumbar disk herniation within 6 months after percutaneous endoscopic lumbar discectomy
Authors: Jia Mengxian , Sheng Yadong , Chen Guoliang , Zhang Wenbin , Lin Jiajin , Lu Sheng , Li Fayi , Ying Jinwei , Teng Honglin 
Published: April 2021

Abstract
Objective
To develop and validate a nomogram useful in predicting recurrent lumbar disk herniation (rLDH) within 6 months after percutaneous endoscopic lumbar discectomy (PELD).

Methods
Information on patients’ lumbar disk herniation (LDH) between January 2018 and May 2019 in addition to 26 other features was collected from the authors’ hospital. The least absolute shrinkage and selection operator (LASSO) method was used to select the most important risk factors. Moreover, a nomogram was used to build a prediction model using the risk factors selected from LASSO regression. The concordance index (C-index), the receiver operating characteristic (ROC) curve, and calibration curve were used to assess the performance of the model. Finally, clinical usefulness of the nomogram was analyzed using the decision curve and bootstrapping used for internal validation.

Results
Totally, 352 LDH patients were included into this study. Thirty-two patients had recurrence within 6 months while 320 showed no recurrence. Four potential factors, the course of disease, Pfirrmann grade, Modic change, and migration grade, were selected according to the LASSO regression model. Additionally, the C-index of the prediction nomogram was 0.813 (95% CI, 0.726-0.900) and the area under receiver operating characteristic curve (AUC) value was 0.798 while the interval bootstrapping validation C-index was 0.743. Hence, the nomogram might be a good predictive model.

Conclusion
Each variable, the course of disease, Pfirrmann grade, Modic change, and migration grade in the nomogram had a quantitatively corresponding risk score, which can be used in predicting the overall recurrence rate of rLDH within 6 months.
Diagnostic delays in vasculitis and factors associated with time to diagnosis
Authors:   for the Vasculitis Patient-Powered Research Network, Sreih Antoine G. , Cronin Keri , Shaw Dianne G. , Young Kalen , Burroughs Cristina , Kullman Joyce , Machireddy Kirthi , McAlear Carol A. , Merkel Peter A. 
Published: April 2021

Abstract
Background
Patients with vasculitis, a set of rare diseases, encounter delays in obtaining an accurate diagnosis which can lead to substantial morbidity and increased mortality. This study sought to describe the diagnostic journey of patients with vasculitis and identify factors associated with time to diagnosis.

Methods
Patients with vasculitis enrolled in an online registry completed a two-stage study: Stage 1: survey of open-ended questions about patients’ diagnostic journeys and perceived factors associated with rapid or delayed diagnosis; Stage 2: survey with specific questions based on data from Stage 1 and additional investigator-identified factors.

Results
375 patients with vasculitis participated in Stage 1; 456 patients participated in Stage 2. 85% of patients were seen by a healthcare provider within 3 months of the onset of symptoms. The median time to diagnosis of vasculitis was 7 months. 313/456 (73%) of patients were misdiagnosed initially. 40% of diagnoses were made in a hospital setting; 2% of diagnoses were made at a specialized vasculitis center. 60% of patients had at least 1 visit to an emergency room prior to diagnosis. Unemployment, time to travel to a medical center > 1 h, initial misdiagnosis, and delays in seeing a specialist were all associated with longer times to diagnosis. 373/456 (82%) of patients reported that a delayed diagnosis had negative consequences on their health.

Conclusion
Patients with vasculitis encounter substantial delays in achieving an accurate diagnosis and these delays are associated with negative health consequences. Both patient-related factors and healthcare-related factors are associated with diagnostic delays.
Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy
Authors: Tang Kai , Wu Ya-Hong , Song Yihui , Yu Bin 
Published: April 2021

AbstractIndoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme that catalyzes the oxidation of L-tryptophan. Functionally, IDO1 has played a pivotal role in cancer immune escape via catalyzing the initial step of the kynurenine pathway, and overexpression of IDO1 is also associated with poor prognosis in various cancers. Currently, several small-molecule candidates and peptide vaccines are currently being assessed in clinical trials. Furthermore, the “proteolysis targeting chimera” (PROTAC) technology has also been successfully used in the development of IDO1 degraders, providing novel therapeutics for cancers. Herein, we review the biological functions of IDO1, structural biology and also extensively summarize medicinal chemistry strategies for the development of IDO1 inhibitors in clinical trials. The emerging PROTAC-based IDO1 degraders are also highlighted. This review may provide a comprehensive and updated overview on IDO1 inhibitors and their therapeutic potentials.