bluuebunny/crossref_metadata_2025_split huggingface dataset:
MACULAR INFARCTION IN A PATIENT WITH SICKLE CELL TRAIT
Authors: Dow Eliot R. , Tsui Irena , Sarraf David 
Published: June 2020

Purpose:
Sickle cell trait affects 8% of African Americans. Once believed to represent a benign carrier state, it has been linked to an increased risk of several of the pathological conditions that arise in sickle cell disease in at-risk individuals with hematologic and vascular comorbidities. Macular infarction is a known complication of sickle cell disease; this article illustrates this unique presentation in a patient with sickle cell trait.

Methods:
Case report.

Patient:
A 74-year-old African American man presented with the complaint of a central scotoma of the right eye.

Results:
Multimodal retinal imaging identified central macular infarction with severe inner retinal atrophy. Laboratory testing confirmed the presence of sickle cell trait. Other pertinent positives included low levels of protein C and protein S, untreated obstructive sleep apnea, and elevated levels of homocysteine in the setting of alcoholic liver cirrhosis and chronic kidney disease.

Conclusion:
Ocular manifestations of sickle cell trait have most frequently been reported in individuals with systemic medical comorbidities that predispose to erythrocyte sickling and vaso-occlusive disease. This case identifies a novel complication of sickle cell trait disorder, macular infarction, in a patient with comorbid associations.
YELLOW SUBRETINAL PIGMENT EPITHELIUM DEPOSITS: A NOVEL SIGN IN OCULAR TUBERCULOSIS
Authors: Agarwal Aniruddha , Aggarwal Kanika , Katoch Deeksha , Invernizzi Alessandro , Arora Atul , Handa Sabia , Sharma Aman , Sharma Kusum , Gupta Vishali 
Published: June 2020

Purpose:
To describe a novel clinical and imaging finding in patients with tubercular posterior uveitis.

Methods:
A retrospective review of 3 cases presented at a tertiary referral eye centre in North India was performed between June 2016 and March 2019. All the patients had received an initial diagnosis of noninfective etiologies (sympathetic ophthalmia, necrotizing scleritis, and lymphoma). Fundus photography, fluorescein angiography, fundus autofluorescence, and enhanced-depth imaging optical coherence tomography were reviewed.

Results:
Three patients (all Asian Indian women: aged 18, 49, and 52 years) diagnosed with panuveitis were investigated for various etiologies based on the initial clinical suspicion. During the course of therapy, all the patients developed peripheral yellow subretinal pigment epithelium deposits (YSRPE) which appeared hypoautofluorescent on fundus autofluorescence and initially hypofluorescent with late hyperfluorescence on fluorescein angiography. The patients were subjected to detailed systemic evaluation and laboratory tests. All the patients showed acid-fast bacilli on invasive tissue biopsies. After initiation of antitubercular therapy, the lesions resolved in all eyes.

Conclusion:
Yellow subretinal pigment epithelium deposits represent a novel and important diagnostic sign of tubercular posterior uveitis.
JUXTAPAPILLARY CAPILLARY RETINAL ANGIOMA AND EPIRETINAL MEMBRANE MANAGEMENT IN A MONOCULAR PATIENT WITH VON HIPPEL–LINDAU SYNDROME
Authors: Schönbach Etienne M. , Trichonas Georgios 
Published: June 2020

Purpose:
To report a case of von Hippel–Lindau syndrome in a monocular patient with progressive vision loss due to a juxtapapillary capillary retinal angioma and an epiretinal membrane (ERM) formation.

Patient:
We describe a 37-year-old white male patient with von Hippel–Lindau syndrome who presented for retinal evaluation. The right eye was blind with no light perception vision. The left eye had a best-corrected visual acuity of 20/30 and exhibited a peripheral capillary hemangioblastoma at 12 o'clock and a juxtapapillary capillary hemangioma with an ERM covering the fovea. The patient underwent two sessions of fluorescein-potentiated argon laser treatment to the peripheral capillary hemangioblastoma with initial stabilization of vision. After 18 months of follow-up, the ERM contracted causing decline in vision to 20/50. Intravitreal injection of bevacizumab was given without improvement in vision or distortion. Twenty-five–gauge pars plana vitrectomy with ERM peeling and internal limiting membrane removal was performed with immediate improvement in vision and distortion.

Conclusion:
This case suggests that pars plana vitrectomy is a reasonable treatment option for vision loss due to a juxtapapillary capillary retinal angioma and ERM formation.
COCCIDIOIDAL ENDOPHTHALMITIS: EXCELLENT RECOVERY OF VISION WITH AGGRESSIVE USE OF INTRAVITREAL ANTIFUNGALS AND VITRECTOMY
Authors: Ahmad Tessnim R. , Li Jonathan , Wu Frances , Rahman Salman , Bever Gregory J. , Afshar Armin R. 
Published: June 2020

Purpose:
To report a case of Coccidioides immitis endophthalmitis with severe vision loss and a return to excellent vision after aggressive intervention.

Methods:
Case report.

Results:
A 41-year-old man with a history of solid organ transplantation who complained of floaters and decreased vision in the setting of disseminated Coccidioides infection was found to have presumed coccidioidal endophthalmitis with visual acuities of 20/20 in the right eye and 20/200 in the left eye. The patient was managed with intravenous amphotericin B, oral voriconazole, and intravitreal injections of amphotericin B and voriconazole in the left eye every three days. Five weeks after presentation, his visual acuity remained 20/20 in the right eye and improved to 20/40 in the left eye. The patient was transitioned to twice weekly intravitreal injections and oral voriconazole on hospital discharge. One week later, vision in the left eye decreased to 20/500 with worsening vitritis, prompting vitrectomy. Vision in the left eye subsequently improved to 20/30. Five weeks later, the patient developed a macula-on inferior rhegmatogenous retinal detachment in the left eye and underwent a second vitrectomy, with scleral buckle, laser, and gas injection. Vision in the left eye returned to 20/25. In total, the patient received 22 amphotericin B and 17 voriconazole intravitreal injections in the left eye with two vitrectomies. Vision in the right eye remained 20/20 throughout his treatment course. At four months after presentation, the patient remained on oral voriconazole with no evidence of active intraocular infection on examination.

Conclusion:
Aggressive medical and surgical management can be successful in ocular conservation and restoration of vision in coccidioidal endophthalmitis. Very mild disease may be conservatively monitored and managed with systemic antifungal therapy alone. In severe disease, early diagnosis and prompt and aggressive use of systemic and intravitreal antifungals may spare panophthalmitis and preserve vision.
DARK WITHOUT PRESSURE IN A CASE OF CHOROIDAL OSTEOMA
Authors: Sherman Tatyana , Palileo Bea M. , Adam Christopher R. , Abrams Gary W. 
Published: June 2020

Purpose:
To report a novel case of dark without pressure in a patient with a choroidal osteoma. To our knowledge, this association has not been previously reported.

Methods:
Observational case report. Review of clinical examination and multi-modal imaging findings in a patient with a choroidal osteoma and dark without pressure.

Results:
A 21-year-old African American woman with no significant past medical history presented with a large, unilateral, juxtapapillary, subretinal, orange-colored, ovoid-shaped lesion with macular involvement. An overlying area of mottled pigmentary changes, fibrosis, and atrophy were present. Adjacent to and surrounding the osteoma was an annular band of hyperpigmented mid-peripheral retina with a sharply demarcated scalloped border that abruptly changed to normal-appearing peripheral retina. Multi-modal imaging including wide-field fluorescein angiography, optical coherence tomography, and ophthalmic B-scan were performed. The funduscopic and imaging findings were consistent with a diagnosis of choroidal osteoma and dark without pressure.

Conclusion:
The examination and imaging findings in this patient suggest a unique association between two relatively uncommon lesions, choroidal osteoma, and dark without pressure. Although these two lesions may simply be coinciding in the same eye, there may be an association with space-occupying lesions causing a change in photoreceptor structure.
SPONTANEOUS CLOSURE OF SECONDARY ECCENTRIC MACULAR HOLES FOLLOWING VITREORETINAL SURGERY
Authors: Venkatesh Ramesh , Pereira Arpitha , Yadav Naresh K. 
Published: June 2020

Purpose:
To report two cases of secondary eccentric macular holes that developed following vitrectomy and present their outcomes.

Methods:
Retrospective, observational case report.

Case Description:
A 69-year-old woman and a 57-year-old man developed secondary paracentral retinal hole following vitrectomy surgery for stage 4 macular hole and proliferative diabetic retinopathy respectively. In Case 1, the hole was left untreated, whereas in Case 2, laser photocoagulation was done around the paracentral retinal hole. In both cases, spontaneous closure of the paracentral retinal holes was noted 12 weeks and 3 weeks after presentation respectively.

Conclusion:
Secondary eccentric retinal holes are extremely rare following vitrectomy. The pathogenesis of macular holes in our cases is most consistent with contraction of the residual internal limiting membrane or preretinal fibrous tissue. Spontaneous closure of small eccentric retinal holes can occur as well which to the best of our knowledge has not yet been reported in literature.
Duration and reliability of the silent period in individuals with spinal cord injury
Authors: Sfreddo Hannah , Wecht Jaclyn R. , Alsalman Ola , Wu Yu-Kuang , Harel Noam Y. 
Published: June 2020

ObjectiveWe aim to better understand the silent period (SP), an inhibitory counterpart to the well-known motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS), in individuals with spinal cord injury (SCI).MethodsElectromyographic responses were measured in the target abductor pollicis brevis at rest (TMS at 120% of resting motor threshold (RMT)) and during maximal effort (TMS at 110% of RMT). Participants with chronic cervical SCI (n=9) and able-bodied volunteers (n=12) underwent between 3-7 sessions of stimulation on separate days. The primary outcomes were the magnitude and reliability of SP duration, resting and active MEP amplitudes, and RMT.ResultsSCI participants showed significantly increased RMT, decreased MEP amplitudes, and non-significantly longer SP duration compared to AB participants. In contrast to high inter-participant variability, SP duration demonstrated reduced intra-participant variability within and across sessions compared with resting and active MEP amplitudes. SCI participants also demonstrated a higher prevalence of SP ‘interruptions’ compared to AB participants.ConclusionsSP reflects a balance between corticospinal excitatory and inhibitory processes. SP duration is more reliable within and across multiple sessions than MEP amplitude.SignificanceThe higher reliability of SP duration may make it a useful outcome measure for future trials of SCI interventions.HighlightsWe compared characteristics of the silent period between individuals with spinal cord injury and able-bodied volunteers.Silent period duration was insignificantly longer in spinal cord injury individuals.Silent period duration was found to be a more reliable within-subject metric than motor evoked potential amplitude.
Thiamine pyrophosphokinase deficiency induces Alzheimer’s pathology
Authors: Sang Shaoming , Qian Ting , Cai Fang , Qiu Hongyan , Xu Yangqi , Zhang Yun , Zhang Qing , Huang Shajin , Jiang Donglang , Wu Yun , Tong Haiyang , Pan Xiaoli , Wang Changpeng , Cheng Xiaoqin , Zhong Kai , Guan Yihui , Zhu Michael X. , Yu Xiang , Song Weihong , Zhong Chunjiu 
Published: June 2020

AbstractBackgroundThiamine diphosphate (TDP) reduction plays an important role in cerebral glucose hypometabolism, the neurodegenerative indicator, in Alzheimer’s disease (AD). The mechanism underlying TDP reduction remains elusive. Thus, it is critical to define the mechanism and its effect on neurodegeneration, the pathological basis of the disease occurrence and progression.MethodsThe mRNA levels of all known genes associated with thiamine metabolism, includingthiamine pyrophosphokinase(TPK),Solute Carrier Family 19 Member 2 (SLC19A2),SLC19A3, andSLC25A19, in brain samples of patients with AD and other neurodegenerative disorders in multiple independent datasets were analyzed. TPK protein levels were further examined in the brain tissues of AD patients and control subjects. A mouse model with conditional knockout (cKO) ofTPKgene in the excitatory neurons of adult brain was established.ResultsThe brainTPKmRNA level was markedly lower in AD patients, but not in other neurodegenerative disorders. The brain TPK protein level was also significantly decreased in AD patients.TPKgene knockout in the mice caused cerebral glucose hypometabolism, β-amyloid deposition, Tau hyperphosphorylation, neuroinflammation, and neuronal loss and brain atrophy. Cross-species correlation analysis revealed the similar changes of gene profiling between the cKO mice and AD patients.ConclusionsThe deficiency of brain TPK, a key enzyme for TDP synthesis, is specific to AD. The cKO mice show AD-associated phenotypes and could serve as a new mouse model for AD studies. Our study provides a novel insight into the critical role of TPK in AD pathogenesis and its potential for the disease treatment.
Temperature-dependent fasciation mutants connect mitochondrial RNA processing to control of lateral root morphogenesis
Authors: Otsuka Kurataka , Mamiya Akihito , Konishi Mineko , Nozaki Mamoru , Kinoshita Atsuko , Tamaki Hiroaki , Arita Masaki , Saito Masato , Yamamoto Kayoko , Hachiya Takushi , Noguchi Ko , Ueda Takashi , Yagi Yusuke , Kobayashi Takehito , Nakamura Takahiro , Sato Yasushi , Hirayama Takashi , Sugiyama Munetaka 
Published: June 2020

AbstractAlthough mechanisms that activate organogenesis in plants are well established, much less is known about the subsequent fine-tuning of cell proliferation, which is crucial for creating properly structured and sized organs. Here we show, through analysis of temperature-dependent fasciation (TDF) mutants of Arabidopsis,root redifferentiation defective 1(rrd1),rrd2, androot initiation defective 4(rid4), that mitochondrial RNA processing is required for limiting cell division during early lateral root (LR) organogenesis. These mutants formed abnormally broadened (i.e., fasciated) LRs under high-temperature conditions due to excessive cell division. All TDF proteins localized to mitochondria, where they were found to participate in RNA processing: RRD1 in mRNA deadenylation, and RRD2 and RID4 in mRNA editing. Further analysis suggested that LR fasciation in the TDF mutants is triggered by reactive oxygen species generation caused by defective mitochondrial respiration. Our findings provide novel clues for the physiological significance of mitochondrial activities in plant organogenesis.
Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis
Authors: Huang He-ming , Fan Shi-jie , Zhou Xiao-ru , Liu Yan-jun , Li Xiao , Liao Li-ping , Huang Jing , Shi Cui-cui , Yu Liang , Fu Rong , Fan Jian-gao , Zhang Yuan-yuan , Luo Cheng , Li Guang-ming 
Published: June 2020

AbstractNon-alcoholic steatohepatitis (NASH) is a common chronic liver disease that causes worldwide morbidity and mortality, yet there is still a lack of pharmacological therapies. Liver inflammation is an important contributor for disease progression from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). We identified HDAC inhibitor givinostat as a potent inhibitor of macrophages inflammatory activation, and aimed to evaluate the therapeutic potential of givinostat for treatment of NASH. Daily administration of givoinostat (10mg/kg) alleviated inflammation and attenuated hepatic fibrosis in methionine- and choline-deficient diet (MCD)-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In hepatocyte givinostat reduced palmitic acid induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in fructose, palmitate, cholesterol diet (FPC) induced NASH mice. Givinostat attenuated hepatic steatosis, inflammation as well as liver injury in FPC-induced NASH. In conclusion, givinostat appears to be efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for treatment of human NASH.
Genomic Profiling Identifies Somatic Mutations Predicting Thromboembolic Risk in Patients with Solid Tumors
Authors: Dunbar Andrew , Bolton Kelly L. , Devlin Sean M. , Sanchez-Vega Francisco , Gao Jianjiong , Mones Jodi V. , Wills Jonathan , Kelly Daniel , Farina Mirko , Cordner Keith , Park Young , Kishore Sirish , Juluru Krishna , Iyengar Neil M. , Levine Ross L. , Zehir Ahmet , Park Wungki , Khorana Alok A. , Soff Gerald A. , Mantha Simon 
Published: June 2020

AbstractCancer-associated venous thromboembolism (CAT) is a well-described complication of cancer and a leading cause of death in cancer patients. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clonal hematopoiesis. We analyzed deep-coverage targeted DNA-sequencing data of >14,000 solid tumor samples using the MSK-IMPACT™ platform to identify somatic alterations associated with VTE. Endpoint was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis. Cause-specific Cox proportional hazards regression was used, adjusting for pertinent clinical covariates. Of 11,695 evaluable individuals, 72% had metastatic disease at time of IMPACT. Tumor-specific mutations in KRAS (HR=1.34 [1.09-1.64]; adjusted p=0.08), STK11 (HR=2.12 [1.55-2.89]; adjusted p<0.001), KEAP1 (HR=1.84 [1.21-2.79]; adjusted p=0.07), CTNNB1 (HR=1.73 [1.15-2.60]; adjusted p=0.09), CDKN2B (HR= 1.45 [1.13-1.85], adjusted p=0.07) and MET (HR=1.83 [1.15-2.92]; adjusted p=0.09) were associated with a significantly increased risk of CAT independent of tumor type. Mutations in SETD2 were associated with a decreased risk of CAT (HR=0.35 [0.16-0.79], adjusted p=0.09). The presence of clonal hematopoiesis was not associated with an increased VTE rate. This is the first large-scale analysis to elucidate tumor-specific genomic events associated with CAT. Somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B and MET were associated with an increased risk of VTE in solid tumor patients. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types.Key PointsTumor mutations in STK11, KRAS, CTNNB1, KEAP1, CDKN2B, MET and SETD2 modulate the risk of cancer-associated thrombosis.The presence of clonal hematopoiesis does not affect the risk of cancer-associated thrombosis.
Clinical validation and performance evaluation of the automated Vitros Total Anti-SARS-CoV-2 Antibodies assay for screening of serostatus in COVID-19
Authors: Garnett Emily , Jung Joanna , Tam Estella , Rajapakshe Deepthi , Cheney Stephen , Brown Cameron , Muldrew Kenneth L. , Cao Jing , Singh Ila , Versalovic James , Devaraj Sridevi 
Published: June 2020

AbstractObjectivesEvaluation of serostatus against SARS-CoV-2 has emerged as an important tool in identification of exposure to COVID-19. We report on the validation of the Vitros Anti-SARS-CoV-2 Total (CoV2T) assay for qualitative serological testing of SARS-CoV-2 antibodies.MethodsWe performed validation studies according to COLA guidelines, using samples previously tested for SARS-CoV-2 by RT-PCR. We evaluated precision, analytical interferences, and cross-reactivity with other viral infections. We also evaluated concordance with molecular and other serological testing, and evaluated seroconversion.ResultsThe Vitros CoV2T assay exhibited acceptable precision, was resistant to analytical interference, and did not exhibit cross-reactivity with samples positive for other respiratory viruses. The CoV2T assay exhibited 100% negative predictive agreement (56/56) and 71% positive predictive agreement (56/79) with RT-PCR across all patient samples, and was concordant with other serological assays. Concordance with RT-PCR was 97% > 7 days after symptom onset.ConclusionsThe Vitros CoV2T assay was successfully validated in our laboratory. We anticipate it will be a useful tool in screening for exposure to SARS-CoV-2, however, the use of the CoV2T and other serological assays in clinical management of COVID-19 patients is yet unknown, and must be evaluated in future studies.Key pointsWhat issue or core problem does the study address?Multiple serological assays for detection of anti-SARS-CoV-2 antibodies have received FDA Emergency Use Authorizations, but few data have been published on the performance of these assays.What would one take-home point for the working medical professional be?The Vitros Anti-SARS-CoV-2 Total assay is a total antibody test to be used as a serological screen for exposure to COVID-19. This assay performs well, and is comparable to other serological tests.What is the most significant or most interesting finding of the study?We confirmed that the Vitros Anti-SARS-CoV-2 Total assay, like other serological tests, is not suitable for diagnosis of acute infection, as it is not sensitive to infection <7 days post-onset.
Use of face coverings in public during the COVID-19 pandemic: an observational study
Authors: Arp Nicholas L. , Nguyen Tung H. , Linck Emma J. Graham , Feeney Austin K. , Schrope Jonathan H. , Ruedinger Katrina L. , Gao Anqi , Miranda-Katz Margot , Kates Ashley E. , Safdar Nasia 
Published: June 2020

AbstractPublic health agencies have recommended that the public wear face coverings, including face masks, to mitigate COVID-19 transmission. However, the extent to which the public has adopted this recommendation is unknown. An observational study of 3,271 members of the public in May and June 2020 examined face covering use at grocery stores across Wisconsin. We found that only 41.2% used face coverings. Individuals who appeared to be female or older adults had higher odds of using face coverings. Additionally, location-specific variables such as expensiveness of store, county-level population and county-level COVID-19 case prevalence were associated with increased odds of using face coverings. To our knowledge, this is the first direct observational study examining face covering behavior by the public in the U.S., and our findings have implications for public health agencies during the COVID-19 pandemic.