bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Logarithmic Reading Charts for Visual Assessment in Normally Sighted Participants
Authors: Maeni Yahya A. , Paterson Kevin B. , Maltby John , McGowan Victoria A. , Hutchinson Claire V. 
Published: January 2022

SIGNIFICANCE
Logarithmic reading charts provide standardized measures of reading performance. Here we show that existing charts provide equivalent assessments of visual aspects of reading that are in good agreement with traditional measures of visual acuity and seem uninfluenced by cognitive (linguistic) factors.

PURPOSE
The aims of this study were to (1) determine the equivalence of logarithmic charts of sentence and word reading, (2) evaluate the relationship between reading chart performance and more traditional measures of visual assessment, and (3) establish the influence of linguistic factors on reading chart performance.

METHODS
In a sample of 82 normally sighted participants, we determined performance on the reading measures (e.g., reading acuity, reading speed, critical print size) of the following logarithmic charts of sentence and word reading: The Colenbrander English Continuous Text Near Vision Card, Radner Reading Chart, Minnesota Reading Acuity Chart, and Smith-Kettlewell Reading Chart. In doing so, we compared performance on reading measures between charts and with performance on more traditional measures of visual assessment (uncrowded and crowded letter acuity, stereoacuity, accommodation) and cognitive measures of word knowledge and ability (Wechsler Adult Intelligence Scale Vocabulary Subtest, National Adult Reading Test).

RESULTS
Factor analysis confirmed that performance on the reading measures (reading acuity, reading speed, critical print size) was equivalent across charts. Reading test performance was also related to more traditional measures of vision, the most consistent of which were significant associations between reading acuity and acuity for single-letter optotypes. There were no significant associations between reading chart performance and cognitive measures of word knowledge and ability.

CONCLUSIONS
The findings presented here suggest that logarithmic charts composed of sentences and words represent an alternative to traditional letter acuity testing. This is particularly the case for measures of reading acuity.
Skin and Soft Tissue Infection Treatment and Prevention Practices by Pediatric Emergency Medicine Providers
Authors: Mistry Rakesh D. , Hogan Patrick G. , Parrish Katelyn L. , Thompson Ryley M. , Fritz Stephanie A. 
Published: January 2022

Objective
The aim of the study was to evaluate skin and soft tissue infection (SSTI) treatment and prevention practices among pediatric emergency medicine (PEM) clinicians in the context of current clinical practice guidelines and contemporary evidence.

Methods
This was a cross-sectional survey of PEM clinicians belonging to the American Academy of Pediatrics Section on Emergency Medicine Survey listserv. Four varying hypothetical clinical scenarios of children with SSTI were posed to respondents; subsequent items assessed SSTI treatment and prevention practices. Provider demographics were collected.

Results
Of 160 survey respondents, more than half stated that they would prescribe oral antibiotics for each clinical scenario, particularly for more complex presentations (small uncomplicated abscess, 51.8%; large uncomplicated abscess, 71.5%; recurrent abscess, 83.5%; febrile abscess, 90.3%; P < 0.001). Most commonly selected antibiotics were clindamycin and trimethoprim-sulfamethoxazole. Across scenarios, more than 80% selected a duration of treatment 7 days or more. Of the 121 respondents who prescribe preventive measures, 85.1% recommend hygiene measures; 52.5% would prescribe decolonization with topical antibiotic ointment and 77.5% would recommend antiseptic body washes. Half of the respondents reported that their institution has standard guidance for SSTI management.

Conclusions
Although current evidence supports adjuvant antibiotics for all drained SSTI and decolonization for the index patient and household contacts, PEM clinicians do not consistently adhere to these recommendations. In light of these findings, development and implementation of institutional guidelines are necessary to aid PEM clinicians' point-of-care decision making and improving evidence-based practice.
The Evolution of Research and Therapy With Hypomethylating Agents in Acute Myeloid Leukemia and Myelodysplastic Syndrome: New Directions for Old Drugs
Authors: Short Nicholas J. , Dombret Hervé , Adès Lionel , Kantarjian Hagop 
Published: January 2022

Abstract
Azacitidine and decitabine are cytosine analogs that function as DNA methyltransferase inhibitors. These agents, commonly referred to as “hypomethylating agents,” are widely used for the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). In this review, we discuss the clinical development of these drugs, including the early studies that led to the optimization of their doses and schedules, and the pivotal studies that led to their regulatory approval, both as monotherapy and in combination with venetoclax for older adults with AML who are unfit for intensive chemotherapy. We also review the more recent development of oral hypomethylating agent formulations and the novel oral strategies being developed in myelodysplastic syndrome and AML.
Evolution of Therapy for Older Patients With Acute Myeloid Leukemia
Authors: Kadia Tapan M. , Wei Andrew H. 
Published: January 2022

Abstract
Most patients with newly diagnosed acute myeloid leukemia (AML) are 65 years or older. The treatment of AML in older patients has been characterized by distinct patient- and disease-related challenges that have impeded the meaningful progress that has been observed in younger patients with AML. Higher rates of comorbidities and frailty contribute to higher rates of treatment-related complications, whereas adverse disease features such as poor-risk genomics and secondary AML are associated with therapeutic resistance and shortened survival. Intensive chemotherapy and allogeneic stem cell transplant, although still considered standard for many newly diagnosed patients with AML, may not be appropriate for a larger subset of older patients with AML. Lower-intensity approaches such as hypomethylating agents have been widely applied for newly diagnosed older and unfit patients with AML, improving tolerability among this subset, but providing more modest response rates. Numerous analyses have attempted to tackle the utility of higher- versus lower-intensity therapy in older AML and identify the factors that can help choose the approach that best optimizes tolerability and efficacy. Recently, a greater understanding of the genomic and biologic heterogeneity of AML has led to better risk stratification and has contributed to the development of specific targeted therapies that are starting to narrow the gap between safety and efficacy. Newly approved agents, such FLT3 (FMS-like tyrosine kinase 3) inhibitors, IDH1 and IDH2 inhibitors, and the BCL2 inhibitor venetoclax, as well postremission maintenance therapy with CC-486 (oral 5-azacitidine), are being systematically incorporated into the evolving treatment of older patients with newly diagnosed AML.
Multiparametric 18F-FDG and 68GA-DOTATOC PET Imaging in Bone Metastatic Meningioma Before Radionuclide Therapy
Authors: Mairal Elise , Chevalier Elodie , Imbert Laetitia , Boursier-Joppin Caroline , Verger Antoine 
Published: January 2022

Abstract
This report presents the case of a 61-year-old woman with assessment of fronto-temporo-sphenoidal refractory meningioma before radionuclide therapy with pretherapeutic 68Ga-DOTATOC PET/CT. Given the discovery of osteolytic lesions, 18F-FDG PET/CT is planned to search for the primitive origin. Meningioma bone metastasis is confirmed with spine biopsies. The presence of dedifferentiated meningioma lesions indicating that high somatostatin receptor expression does not necessarily coincide with areas of increased glucose metabolism. 18F-FDG and 68Ga-DOTATOC PET/CT allows optimal characterization of tumor heterogeneity and guide targeted therapeutic management before PPRT.
Bacteriological Investigation and Drug Resistance Analysis of Chronic Refractory Wound Secretions
Authors: Dong Xiang-Mei , Pei Li-Li , Lu Peng-Song , Ni Peng , Yu Bao-Fu , Fan Zhi-Qiang 
Published: January 2022

Background:
Chronic refractory wounds were common and the treatments were complicated for burn and plastic surgeons. This study was to investigate the bacterial distribution characteristics and bacterial drug resistance of chronic refractory wound secretions.

Methods:
The authors retrospectively analyzed 425 patients with chronic refractory wound infection. The results of bacterial culture of wound secretions and drug sensitivity test were retrospectively analyzed. Further, the location area of the wound was divided into 4 regions, and the difference of the bacterial culture results between different regions was analyzed.

Results:
The wound secretions were cultured into 401 bacterial strains, including 206 gram-positive bacteria strains, accounting for 51.4%, with the highest detection rate of Staphylococcus aureus at 26.2% (105/401). There were 195 gram-negative bacteria strains, accounting for 48.6%, with the highest detection rate of Pseudomonas aeruginosa at 14.2% (57/401). There were 6 fungal strains. The proportion of gram-negative bacteria in the III region of the wound zone was significantly greater than that in the other 3 regions.

Conclusions:
The detection rate of gram-positive bacteria and gram-negative bacteria of chronic refractory wound secretions is not much different. However, in the area close to the perineum (III region), gram-negative bacteria is significantly higher, which has a certain reference value for the use of antibiotics in clinical practice.

Level of evidence:
Level 4.
Intraoperative Neurophysiological Monitoring Alerts During Three-Column Osteotomy: Incidence and Risk Factors
Authors: Liu Wanyou , Qiu Junyin , Zhu Zezhang , Shi Benlong , Li Yang , Liu Zhen , Sun Xu , Qiu Yong 
Published: January 2022

Prupose:
To analyze the incidence and risk factors of intraoperative neurophysiological monitoring (IONM) alerts in patients undergoing three-column osteotomy.

Methods:
A total of 551 patients (340 males and 211 females) with an average age of 31.9 years undergoing posterior 3-column osteotomy were retrospectively reviewed. The coronal Cobb angle of main curve and sagittal global kyphosis were measured on preoperative standing whole spinal x-rays. The Frankel scores at preoperation, postoperation, and the last follow-up were recorded and applied for assessment of neurologic status. Surgical procedures and other factors associated with IONM alerts were analyzed.

Results:
A total of 98 (17.8%) IONM alerts were reported during surgery, including 82 somatosensory evoked potential alerts and 91 motor evoked potential alerts. Positive wake-up test was revealed in 57 patients (10.3%) even after prompt managements, and new neurologic deficits were observed in 50 patients (9.1%) at immediate postoperation. Of the 50 patients with new neurologic deficits at postoperation, the Frankel scores were A in 5 patients, B in 4, C in 9, and D in 32. The χ2 test showed that patients with congenital deformities, global kyphosis >90°, vertebral column resection procedure, cervicothoracic/thoracic osteotomy, blood loss >3,000 mL, and preoperative neurologic deficit were at a higher risk of IONM alerts.

Conclusions:
The incidence of IONM alerts in patients undergoing 3-column osteotomy was 17.8%. Congenital deformities, global kyphosis >90°, vertebral column resection, cervicothoracic/thoracic osteotomy, blood loss >3,000 mL, and preoperative neurologic deficit indicated high risk of IONM alerts.
Detection and upsurge of SARS-CoV-2 Omicron variant in Islamabad Pakistan
Authors: Umair Massab , Ikram Aamer , Rehman Zaira , Haider Syed Adnan , Badar Nazish , Ammar Muhammad , Ali Qasim , Ahad Abdul , Suleman Rana , Khalid Ayesha , Tariq Amna , Jamal Zunera , Salman Muhammad 
Published: January 2022

AbstractThe SARS-CoV-2 omicron variant was first detected in South Africa in November, 2021 and has rapidly spread to more than 90 countries. The emergence of Omicron variant demands for enhanced genomic surveillance to track the mutation profile and spread of virus. In the current study, we have sequenced 15 whole-genome sequences of SARS-CoV-2 Omicron variant from Islamabad region of Pakistan. Among the 15 isolates, 66% were from Islamabad whereas 33% of cases had international travel history of United Kingdom, Maldives, South Africa, and Oman. The detection of Omicron in local community and in travelers highlights the need for rigorous screening at national level and at entry points in order to contain the spread of variant.
A family of C. elegans VASA homologs control Argonaute pathway specificity and promote transgenerational silencing
Authors: Dai Siyuan , Tang Xiaoyin , Li Lili , Ishidate Takao , Ozturk Ahmet R , Chen Hao , Yan Yonghong , Dong Mengqiu , Shen Enzhi , Mello Craig C 
Published: January 2022

ABSTRACTGermline Argonautes direct transcriptome surveillance within peri-nuclear membraneless organelles called nuage. In C. elegans, a family of Vasa-related Germ Line Helicase (GLH) proteins localize in, and promote the formation of nuage called P granules. Previous studies have implicated GLH proteins in inherited silencing but direct roles in amplification of small RNAs, or in target mRNA or Argonatue binding have not been identified. Here we show that GLH proteins compete with each other to control Argonaute pathway specificity, bind directly to Argonaute-target mRNAs and act to promote the amplification of small RNAs required for transgenerational inheritance. We show that the ATPase cycle of GLH-1 regulates its direct binding to the Argonaute WAGO-1 which engages amplified small RNAs. Our findings support a dynamic and direct role for GLH proteins in inherited silencing beyond their role as structural components of nuage.
The Alzheimer’s disease risk gene BIN1 modulates neural network activity via the regulation of L-type calcium channel expression in human-induced neurons
Authors: Saha Orthis , Melo de Farias Ana Raquel , Pelletier Alexandre , Siedlecki-Wullich Dolores , Gadaut Johanna , Landeira Bruna Soares , Carrier Arnaud , Vreulx Anaïs-Camille , Guyot Karine , Bonnefond Amelie , Amouyel Philippe , Queiroz Cláudio Marcos , Kilinc Devrim , Delahaye Fabien , Lambert Jean-Charles , Costa Marcos R. 
Published: January 2022

AbstractBackgroundBridging Integrator 1 (BIN1) is the second most important Alzheimer’s disease (AD) risk gene, but its physiological roles in neurons and its contribution to brain pathology remain largely elusive. In this work, we show that BIN1 plays a critical role in the regulation of calcium homeostasis, electrical activity, and gene expression of glutamatergic neurons.MethodsWe generated 3D cerebral organoids and 2D enriched neuronal cell cultures from isogenicBIN1wild-type (WT), heterozygous (HET) and homozygous knockout (KO) human-induced pluripotent stem cells (hiPSCs). Using single-cell RNA-sequencing, biochemical assays, immunocytochemistry and multi-electrode array(MEA) electrophysiology, we characterized the molecular and functional consequences of reduced BIN1 expression in different neural cell types.ResultsWe show thatBIN1is mainly expressed by oligodendrocytes and glutamatergic neurons of cerebral organoids, like in the human brain. BothBIN1HET and KO cerebral organoids show specific transcriptional alterations, mainly associated with ion transport and synapses in glutamatergic neurons. We then demonstrate thatBIN1cell-autonomously regulates gene expression in glutamatergic neurons by using a novel protocol to generate pure culture of human-derived induced neurons (hiNs). Using this system, we also show that BIN1 plays a key role in the regulation of neuronal calcium transients and electrical activity via its interaction with the L-type voltage-gated calcium channel Cav1.2.BIN1KO hiNs show reduced activity-dependent internalization and higher Cav1.2expression compared to WT hiNs. Pharmacological treatment with clinically relevant doses of nifedipine, a calcium channel blocker, partly rescues neuronal electrical and gene expression alterations inBIN1KO glutamatergic neurons. Further, we show that transcriptional alterations inBIN1KO hiNs affecting biological processes related to calcium homeostasis are also present in glutamatergic neurons of the human brain at late stages of AD pathology.ConclusionsTogether, our findings suggest that BIN1-dependent alterations in neuronal properties could contribute to AD pathophysiology and that treatment with low doses of clinically approved calcium blockers should be considered as an option to dampen disease onset and progression.
How a Formate Dehydrogenase Responds to Oxygen: Unexpected O2 Insensitivity of an Enzyme Harboring Tungstopterin, Selenocysteine, and [4Fe-4S] Clusters
Authors: Graham Joel E. , Niks Dimitri , Zane Grant M. , Gui Qin , Hom Kellie , Hille Russ , Wall Judy D. , Raman C. S. 
Published: January 2022

ABSTRACTThe reversible two-electron interconversion of formate and CO2 is catalyzed by both non-metallo and metallo-formate dehydrogenases (FDHs). The latter group comprises molybdenum-or tungsten-containing enzymes with the metal coordinated by two equivalents of a pyranopterin cofactor, a cysteinyl or selenocysteinyl ligand supplied by the polypeptide, and a catalytically essential terminal sulfido ligand. In addition, these biocatalysts incorporate one or more [4Fe-4S] clusters for facilitating long-distance electron transfer. But an interesting dichotomy arises when attempting to understand how the metallo-FDHs react with O2. Whereas existing scholarship portrays these enzymes as being unable to perform in air due to extreme O2 lability of their metal centers, studies dating as far back as the 1930s emphasize that some of these systems exhibit formate oxidase (FOX) activity, coupling formate oxidation to O2 reduction. Therefore, to reconcile these conflicting views, we explored context-dependent functional linkages between metallo-FDHs and their cognate electron acceptors within the same organism vis-à-vis catalysis under atmospheric conditions. Here, we report the discovery and characterization of an O2-insensitive FDH2 from the sulfate-reducing bacterium Desulfovibiro vulgaris Hildenborough that ligates tungsten, selenocysteine, and four [4Fe-4S] clusters. Notably, we advance a robust expression platform for its recombinant production, eliminating both the requirement of nitrate or azide during purification and reductive activation with thiols and/or formate prior to catalysis. Because the distinctive spectral signatures of formate-reduced DvH-FDH2 remain invariant under anaerobic and aerobic conditions, we benchmarked the enzyme activity in air, identifying CO2 as the bona fide product of catalysis. Full reaction progress curve analysis uncovers a high catalytic efficiency when probed with an artificial electron acceptor pair. Furthermore, we show that DvH-FDH2 enables hydrogen peroxide production sans superoxide release to achieve O2 insensitivity. Direct electron transfer to cytochrome c in air also reveals that electron bifurcation is operational in this system. Taken together, our work unambiguously proves for the first time the coexistence of redox bifurcated FDH and FOX activities within a metallo-FDH scaffold. These findings have important implications for engineering O2-tolerant FDHs and bio-inspired artificial metallocatalysts, as well as for the development of authentic formate/air biofuel cells, modulation of catalytic bias, assessing the limits of reversible catalysis, understanding directional electron transfer, and discerning formate bioenergetics of gut microbiota.
The synaptic vesicle protein Mover/TPRG1L is associated with lipid droplets in astrocytes
Authors: Krohn Jeremy , Domart Florelle , Do Thanh Thao , Dresbach Thomas 
Published: January 2022

AbstractCrucial brain functions such as neurotransmission, myelination, and signaling pose a high demand for lipids. Lipid dysregulation is associated with neuroinflammation and neurodegeneration. Astrocytes protect neurons from lipid induced damage by accumulating and metabolizing toxic lipids in organelles called lipid droplets (LDs). LDs have long been considered as lipid storage compartments in adipocytes, but less is known about their biogenesis and composition in the brain. In particular, proteins covering the LD surface are not yet fully identified.Here, we report that the synaptic vesicle protein Mover/TPRG1L, which regulates the probability of neurotransmitter release in neurons, is a component of the LD coat in astrocytes. Using conventional and super resolution microscopy, we demonstrate that Mover surrounds naive and oleic acid induced astrocytic LDs. We confirm the identity of astrocytic LDs using the neutral lipid stains Bodipy and LipidTox, as well as immunofluorescence for perilipin-2, a known component of the LD coat. In astrocytes, recombinant Mover was sufficient to induce an accumulation of LDs. Furthermore, we identified point mutations that abolish targeting to LDs and show similarities in the required binding sequences for association to the presynapse and LDs.Our results show that Mover is not only a presynaptic protein but also a candidate for LD regulation. This highlights the dual role of Mover in synaptic transmission and regulation of astrocytic LDs, which may be particularly important in the context of lipid-related neurological disorders.Main points- Mover is a lipid droplet protein- Overexpression of Mover drives lipid droplet accumulation- The F206 is important for LD targeting