bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysing the radio flux density profile of the M31 galaxy: a possible dark matter interpretation
Authors: Chan Man Ho , Yeung Chu Fai , Cui Lang , Leung Chun Sing
Published: December 2020

Some recent studies have examined the gamma-ray flux profile of our Galaxy to determine the signal of dark matter annihilation. However, the results are controversial and no confirmation is obtained. In this article, we study the radio flux density profile of the M31 galaxy and show that it could manifest a possible signal of dark matter annihilation. By comparing the likelihoods between the archival observed radio flux density profile data and the predicted radio flux density profile contributed by dark matter and stellar emission, we can constrain the relevant dark matter parameters. Specifically, for the thermal annihilation cross section via the $b\bar{b}$ channel, the best-fit value of dark matter mass is ∼30 GeV, which is consistent with the results of many recent studies. We expect that this method would become another useful way to constrain dark matter, which is complementary to the traditional radio analyses and the other indirect detections.
Constraining the shear acceleration model for the X-ray emission of large-scale extragalactic jets
Authors: Tavecchio F
Published: December 2020

The nature of the intense X-ray emission from powerful extragalactic jets at large (>1 kpc) scale is still debated. The scenario that invokes the inverse Compton scattering of the cosmic microwave background by electrons is challenged by the lack of gamma-ray emission in the GeV band. An alternative assumes synchrotron emission by a distinct population of ultra-high energy electrons. Here, we present a concrete attempt to apply this scenario, exploring the specific model in which the ultra-high energy electrons are accelerated in a shear layer surrounding the jet. We limit the study to non-relativistic flows and particle acceleration is treated by a Fokker–Planck equation. The observed relation between low energy (radio, optical) and X-ray emission prompts us to assume that the required population of pre-accelerated particles is provided by a shock responsible for the acceleration of the electrons emitting at low frequencies. We apply the model to the emission of the principal knots of the jets of PKS 0637–752 and PKS 1136–135, two of the best-studied objects. For the set of fiducial parameters adopted, the condition that the jet power does not exceeds a limiting value of 1048 erg s−1 constrains the magnetic field above $10\, \mu$G and indicates moderate beaming (δ ≃ 2) for PKS 0637–752. For both sources, the requirement that acceleration of the electrons proceeds faster than radiative cooling can be met if the magnetic turbulence in the shear layer follows a Kolmogorov spectrum, I(k) ∝ k−q with q = 5/3, but cannot satisfied in the Bohm-like case (q = 1).
RPA complexes inCaenorhabditis elegansmeiosis; unique roles in replication, meiotic recombination and apoptosis
Authors: Hefel Adam , Honda Masayoshi , Cronin Nicholas , Harrell Kailey , Patel Pooja , Spies Maria , Smolikove Sarit
Published: December 2020

Replication Protein A (RPA) is a critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) that form a trimeric complex critical for viability. The Caenorhabditis elegans genome encodes RPA-1, RPA-2 and an RPA-2 paralog RPA-4. In our analysis, we determined that RPA-2 is critical for germline replication and normal repair of meiotic DSBs. Interestingly, RPA-1 but not RPA-2 is essential for somatic replication, in contrast to other organisms that require both subunits. Six different hetero- and homodimeric complexes containing permutations of RPA-1, RPA-2 and RPA-4 can be detected in whole animal extracts. Our in vivo studies indicate that RPA-1/4 dimer is less abundant in the nucleus and its formation is inhibited by RPA-2. While RPA-4 does not participate in replication or recombination, we find that RPA-4 inhibits RAD-51 filament formation and promotes apoptosis of a subset of damaged nuclei. Altogether these findings point to sub-functionalization and antagonistic roles of RPA complexes in C. elegans.
Guide-target mismatch effects on dCas9–sgRNA binding activity in living bacterial cells
Authors: Feng Huibao , Guo Jiahui , Wang Tianmin , Zhang Chong , Xing Xin-hui
Published: December 2020

As an effective programmable DNA targeting tool, CRISPR–Cas9 system has been adopted in varieties of biotechnological applications. However, the off-target effects, derived from the tolerance towards guide-target mismatches, are regarded as the major problems in engineering CRISPR systems. To understand this, we constructed two sgRNA libraries carrying saturated single- and double-nucleotide mismatches in living bacteria cells, and profiled the comprehensive landscape of in vivo binding affinity of dCas9 toward DNA target guided by each individual sgRNA with particular mismatches. We observed a synergistic effect in seed, where combinatorial double mutations caused more severe activity loss compared with the two corresponding single mutations. Moreover, we found that a particular mismatch type, dDrG (D = A, T, G), only showed moderate impairment on binding. To quantitatively understand the causal relationship between mismatch and binding behaviour of dCas9, we further established a biophysical model, and found that the thermodynamic properties of base-pairing coupled with strand invasion process, to a large extent, can account for the observed mismatch-activity landscape. Finally, we repurposed this model, together with a convolutional neural network constructed based on the same mechanism, as a predictive tool to guide the rational design of sgRNA in bacterial CRISPR interference.
Secondary infection of amoeba and typhoid fever in severe malnourished pediatric patient with Type I choledocal cyst: a case report
Authors: Adrizain Riyadi , Aprimadhansari  , Indriasari Vita , Kusmayadi Dikki Drajat , Setiabudi Djatnika
Published: December 2020

Amebiasis is caused by the protozoan Entamoeba histolytica. Extraintestinal amebiasis manifestation includes liver abscess and other rare manifestations involving the lungs, heart and brain. Liver abscess is the most common extraintestinal manifestation. Only few cases of amebic splenic abscess and two cases of gall bladder abscess have been reported. Typhoid fever is an infection caused by Salmonella typhi. It can cause extraintestinal complications such as myocarditis, endocarditis, pneumonia, empyema, osteomyelitis, arthritis, cholecystitis, spleen abscess and liver abscess. Choledocal cyst is a congenital dilation of the biliary branch. If left untreated, it can cause morbidity from cholangitis, cyst perforation, liver failure and malignancy. Until now, there is no publication about double infection of amebic and salmonella infection in a child with choledocal cyst.
Point-of-care ultrasound diagnosis of flexor tenosynovitis caused by an unusual pathogen
Authors: Yates Margaret C , Chiasson Katherine F , Pacheco Zachary S , Gullett John P , Denney Brad D , Pigott David C
Published: December 2020

Skin and soft tissue infections are commonly encountered in the emergency department and are typically caused by common gram-positive bacteria. In the immunocompromised patient, however, infections from unusual pathogens should also be considered. We describe the case of a 66-year-old male with a history of renal transplant who was diagnosed with flexor tenosynovitis by point-of-care ultrasound. Although initial wound cultures were negative, subsequent microbiological testing led to the underlying cause, a nontuberculous mycobacterial infection.
Anterior Cervical Discectomy With Fusion and Plating for Correction of Degenerative Cervical Kyphosis: 2-Dimensional Operative Video
Authors: Guinn Jeremy M V , Pennicooke Brenton , Rivera Joshua , Mummaneni Praveen V , Chou Dean
Published: December 2020

This surgical video demonstrates the technique for correcting degenerative cervical kyphosis using an anterior cervical discectomy and fusion (ACDF). Degenerative cervical kyphosis can cause radiculopathy, myelopathy, and difficulty holding up one's head. The goal of surgical intervention is to alleviate pain, improve the ability for upright gaze, and decompress the spinal cord or nerve roots. Posterior-only approaches and anterior corpectomies are alternative treatments to address cervical kyphosis. However, an ACDF allows for sequential induction of lordosis via distraction over multiple segments and for further lordosis induction by sequential screw tightening, pulling the spine towards a lordotic cervical plate.
1
This video shows 2 cases demonstrating a technique of correcting severe cervical degenerative kyphosis. The video illustrates our initial kyphotic Caspar pin placement coupled with sequential anterior distraction to correct kyphosis. The technique is most useful in patients who have good bone density, nonankylosed facets, and degenerative cervical kyphosis. We have received informed consent of this patient to submit this video.
Resection of Ventral Thoracic Calcified Meningiomas Through a Transpedicular Approach: 2-Dimensional Operative Video
Authors: Galgano Michael A , Hoffman Haydn
Published: December 2020

The surgical resection of ventrally located thoracic lesions carries additional complexity because of the constraints of the mediastinum and pleural cavity as well as the intolerance of the spinal cord to manipulation. The creation of a ventrolateral operative corridor through a transpedicular, transarticular route is effective for accessing the ventral thoracic spinal cord. This operative video demonstrates the surgical management of a 67-yr-old female who presented with progressive gait ataxia and bilateral lower extremity weakness and was found to have noncontiguous calcified ventral thoracic meningiomas at T6 and T10. The surgical plan consisted of T4-11 posterior instrumentation, T5-6 and T9-10 laminectomies with unilateral facetectomies and pediculectomies at both segments, and microsurgical resection of both tumors. Postoperatively, the patient's gait and paraparesis improved. Although instrumentation is infrequently utilized when managing intradural pathology, it permitted aggressive bone removal in order to create an unobstructed ventrolateral corridor to the tumor. This allowed us to perform generous durotomies spanning the length of each lesion and obviated the need for spinal cord manipulation during tumor resection. The patient provided informed consent for the surgery and video recording, and institutional review board approval was determined to be unnecessary.
The interface of multisectoral and multilateral dimensions of public health policy: what’s new in the 21st century?
Authors: Nikogosian Haik
Published: December 2020

The article examines key developments unfolding in the 21st century in the intersection of multisectoral and multilateral dimensions of public health policy. Several processes and mechanisms, relatively new or rapidly evolving, are fuelling this dynamic interface. They include, in particular, expansion of the spectrum of sectors involved in the health domain, the upsurge of trans-border and commercial determinants of health, growing presence of health issues in multilateral instruments and processes that are outside of the health sector, and strengthening the legal base of intersectoral relations and responsibilities for health. They also encompass and reflect important transformations in health diplomacy and governance for health, some of the fundamentals of contemporary public and global health. The article argues that overall, multisectoral and multilateral dimensions tend to interact, inform and reinforce each other, and that such interaction would be one of important drivers of 21st century intersectoral policy—and international cooperation—for health.
Flat Connections and the Commutator Map for SU(2)
Authors: Ho Nan-Kuo , Jeffrey Lisa C , Selick Paul , Xia Eugene Z
Published: December 2020

We study the topology of the SU(2)-representation variety of the compact oriented surface of genus 2 with one boundary component about which the holonomy is a generator of the center of SU(2).
RESEARCH ON THE ABSOLUTE MEASUREMENT AND CALIBRATION METHODS OF (250–450) KV X-RAY AIR KERMA AT NIM
Authors: Zhao Rui , WU Jin-Jie , XU Yang , REN Guo-Yue , DU Hai-Yan , YU Ji-Li , CHE Wei-Na
Published: December 2020

With the rapid application of nuclear technology, radiation protection is becoming more and more important. For external radiation protection, most of the national metrology institutes in the world have established the primary standard of X-ray air kerma in (10–250) kV and Cs-137 gamma ray, but the energy between 250 and 662 keV needs the establishment of traceability. To provide solution to such issue, a graphite cavity ionization chamber was constructed at National Institute of Metrology to measure the air kerma in (250–450) kV X-ray. The relative standard uncertainty of the method is 0.45%. Two different types of ionization chambers were used to measure the air kerma of N-300 radiation quality, and the result has a deviation of 0.09%.
The New Milk Carton Campaign: An Analysis of Social Media Engagement with Missing Persons’ Cases
Authors: Jeanis Michelle N , Powers Ráchael A , Miley Lauren N , Shunick Charlene E , Storms Margaret
Published: December 2020

The unique feature of social media as a platform for news is that the public can directly engage with content. In this way, the public shapes the narrative on current issues, including crime. Criminal justice agencies have leveraged this engagement to relay information about missing persons’ cases quickly and efficiently to a large audience. Whereas previous research has explored disparities in news coverage of missing persons’ cases, it is unknown whether the public perpetuates these same disparities in the social media realm. This study contributes to the current literature by examining public engagement with missing persons’ social media content. Results suggest that engagement along some dimensions corresponds to disparities found in traditional news coverage, namely with regard to race, where marginalized victims experience less engagement. Further, there is evidence of an interaction between race and runaway status. Certain posting behaviors are also related to several forms of user engagement with missing persons’ posts; however, case characteristics remain prominent engagement-shaping factors. Implications for these findings are discussed from both a theoretical and practitioner standpoint.
Use of modelling to modify trachoma elimination strategies affected by the COVID-19 pandemic
Authors: Emerson Paul M , Hooper P J , Gebre Teshome
Published: December 2020

Models predict that the negative effects of delayed implementation in trachoma elimination programmes caused by the COVID-19 pandemic will be minimal, except in high prevalence districts where progress may be reversed. During times of change we must stand by our principles of evidence-based decision-making, but also be willing to show flexibility. Slow progress to elimination in high prevalence districts was already a significant challenge to the global programme and mitigation of COVID-related delays with enhanced implementation provides an opportunity to simultaneously address an unprecedented challenge and a pre-existing one.
Development of an Inoculation Technique for Rapidly Evaluating Maize Inbred Lines for Resistance to Stalk Rot caused by Fusarium spp. in the Field
Authors: Jiang Wanyi , Han Wenbo , Wang Ruiting , Li Yonggang , Hu Guanghui , Yang Jianfei , Jiang Dan , Han Wenhao , Wang Mingquan , Li Guoliang
Published: December 2020

Maize (Zea mays L.) stalk rot, caused primarily by the soilborne fungal pathogen Fusarium spp., reduces maize quality and yield worldwide. This study was undertaken to develop and utilize a rapid continuous injection inoculation technique to evaluate maize inbred lines for resistance to Fusarium spp. under field conditions, which could facilitate the identification and development of new sources of host resistance to manage the disease. Continuous injection inoculation is a rapid, stable, and simple method that can evaluate the resistance of maize inbred lines to Fusarium stalk rot (FSR) within 20 days. To verify the feasibility and reliability of the inoculation method, Fusarium graminearum, F. proliferatum, and F. subglutinans were isolated, identified, and inoculated into maize at the six-leaf stage (V6) by a veterinary adjustable bottle continuous vaccination syringe. Our results showed that, of a total of 97 inbred maize lines, 6 (6.2%) showed high resistance to maize stalk rot, 20 showed resistance (20.6%), 32 were susceptible (33.0%), and 39 were very susceptible (40.2%). Based on simple sequence repeat markers, an analysis of molecular variance indicated a significant correlation between population of the inbred maize line and resistance to FSR (P = 0.001). Overall, this study provided a systematic, rapid, stable, and simple identification method for maize inbred lines resistant to FSR in the field. At the same time, this method was also suitable for genetic diversity analysis of maize inbred lines resistant to FSR.
Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain
Authors: Ilfeld Brian M. , Eisenach James C. , Gabriel Rodney A.
Published: December 2020

The authors provide a comprehensive summary of all randomized, controlled trials (n = 76) involving the clinical administration of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, USA) to control postoperative pain that are currently published. When infiltrated surgically and compared with unencapsulated bupivacaine or ropivacaine, only 11% of trials (4 of 36) reported a clinically relevant and statistically significant improvement in the primary outcome favoring liposomal bupivacaine. Ninety-two percent of trials (11 of 12) suggested a peripheral nerve block with unencapsulated bupivacaine provides superior analgesia to infiltrated liposomal bupivacaine. Results were mixed for the 16 trials comparing liposomal and unencapsulated bupivacaine, both within peripheral nerve blocks. Overall, of the trials deemed at high risk for bias, 84% (16 of 19) reported statistically significant differences for their primary outcome measure(s) compared with only 14% (4 of 28) of those with a low risk of bias. The preponderance of evidence fails to support the routine use of liposomal bupivacaine over standard local anesthetics.
Association of Lumbar Spinal Stenosis with Severe Disability and Mortality Among Community-Dwelling Older Adults
Authors: Hijikata Yasukazu , Kamitani Tsukasa , Otani Koji , Konno Shinichi , Fukuhara Shunichi , Yamamoto Yosuke
Published: December 2020

Study Design.

This prospective cohort study analyzed data from the Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study.

Objective.

To investigate the association between lumbar spinal stenosis (LSS) and severe disability and mortality among community-dwelling older adults.

Summary of Background Data.

Only a few studies have investigated LSS longitudinally, and the study participants were limited to selected patients diagnosed with LSS during a hospital visit. Additionally, the prognosis of LSS remains unclear.

Methods.

We enrolled independent community-dwelling older adults aged 65 years or older at the time of a baseline health checkup in 2008. LSS was diagnosed using a validated diagnostic support tool for LSS. The primary endpoint was a composite of severe disability (long-term care insurance certification grade 4 or 5) and mortality. We used 1 minus Kaplan–Meier failure estimates and the log-rank test to compare the interval between baseline and the predetermined endpoint as well as a Cox proportional hazards model to estimate hazard ratios (HRs) for the LSS group with adjustment for possible confounders. Multiple imputation by chained equations was performed for sensitivity analysis.

Results.

Of 2058 subjects enrolled, 1560 did not have missing covariates; 269 (17%) were diagnosed with LSS. After a median follow-up of 5.8 years, the rates of severe disability and mortality were 0.022 per year in subjects with LSS and 0.012 per year in those without (P = 0.006). The adjusted HR for the composite endpoint in the LSS group was 1.55 (95% confidence interval [CI], 1.01–2.38). A similar association was observed after multiple imputation of missing covariates (adjusted HR, 1.51 [95% CI, 1.06–2.16]).

Conclusion.

LSS was associated with severe disability and mortality in community-dwelling older adults. Detection of adults with LSS in the community may contribute to local health promotion.

Level of Evidence: 2
Transanal Minimally Invasive Proctectomy With Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Iatrogenic Rectourethral Fistulas
Authors: Martín-Pérez Beatriz , Dar Ron , Bislenghi Gabriele , Stijns Jasper , Grégoir Tine , Wolthuis Albert M. , D´Hoore André
Published: December 2020

INTRODUCTION:

Rectourethral fistula is an uncommon pathology, usually iatrogenic, occurring as a complication of surgical or ablative treatments for prostate or rectal cancer. Among other surgical techniques, restorative ultralow rectal anterior resection may be an option of last resort to achieve fistula closure avoiding the need for a permanent stoma. This article aims to describe a transanal minimally invasive-assisted Turnbull-Cutait technique for radiated rectourethral fistulas with a complementary video.

TECHNIQUE:

Turnbull-Cutait pull-through with delayed coloanal anastomosis technique with a proctectomy by transanal minimally invasive surgery and loop ileostomy was performed in 3 patients who developed delayed rectourethral fistula after prostate cancer treatment. Ileostomy was reversed after fistula closure confirmation.

RESULTS:

The first patient had brachytherapy with no surgery. The second patient had radical prostatectomy and adjuvant radiotherapy, developing the fistula after a pelvic abscess drained transrectally. The third patient underwent prostatectomy and brachytherapy, developing the fistula after transanal endoscopic microsurgery resection of a rectal villous polyp. Surgical intervention and postoperative recovery was uneventful. Fistula closure was confirmed in the 3 cases, and all ileostomies were closed without further recurrence at follow-up.

CONCLUSIONS:

Transanal minimally invasive proctectomy-assisted Turnbull-Cutait procedure for the treatment of rectourethral fistula is a new combination of already existing techniques, enabling the creation of safe colorectal anastomosis in high-risk cases. Given the difficulty obtaining healing with sphincter preservation in cases of postradiation rectourethral fistula, this technique aids in fistula closure and restoration of the intestinal continuity, and potentially represents an added resource in the surgical armamentarium for this challenging pathology.
VOGT–KOYANAGI–HARADA-LIKE UVEITIS FOLLOWED BY MELANOMA-ASSOCIATED RETINOPATHY WITH FOCAL CHORIORETINAL ATROPHY AND CHOROIDAL NEOVASCULARIZATION IN A PATIENT WITH METASTATIC CUTANEOUS MELANOMA
Authors: Ng Caleb C. , Alsberge Joseph B. , Qian Ying , Freund K. Bailey , Cunningham Emmett T.
Published: December 2020

Purpose:

To report a case of Vogt–Koyanagi–Harada-like uveitis followed by melanoma-associated retinopathy with focal chorioretinal atrophy and subsequent choroidal neovascularization in a patient with metastatic cutaneous melanoma.

Method:

Case report. Main outcome measures include external photography, anterior segment photography, ophthalmoscopic examination, fundus photography, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography, optical coherence tomography angiography, and electroretinography.

Results:

A 68-year-old man with a history cutaneous melanoma presented with Vogt–Koyanagi–Harada-like uveitis. Work-up revealed a pelvic mass, which was excised and found to be metastatic melanoma. Two years later, the patient developed melanoma-associated retinopathy with focal chorioretinal atrophy and adjacent choroidal neovascularization.

Conclusion:

Patients with metastatic cutaneous melanoma can develop distinct and sequential paraneoplastic ocular complications. Onset of a Vogt–Koyanagi–Harada-like uveitis may be a good prognostic factor for survival in patients with metastatic cutaneous melanoma.
Outcomes of COVID-19 Patients Hospitalized at Acute Care Services
Authors: Marsh Kassandra , Decano Arnold , Siegfried Justin , Ahmed Nabeela , Blum Sharon , Tirmizi Samad , Dong Mei Qin , Mehta Dhara , Pham Vinh P. , Papadopoulos John , Dubrovskaya Yanina
Published: December 2020

Background

As New York became the epicenter of the COVID-19 pandemic early on, clinicians were challenged to provide optimal medical and pharmaceutical care, despite the paucity of supporting literature and guidance. We sought to describe prescribing patterns and outcomes of physician response to the urgent need to treat COVID-19 patients before initiation of randomized clinical trials.

Methods

This was a retrospective cohort study of adult patients with COVID-19 initially admitted to acute care services during March 2020. Critically ill patients requiring intensive care unit level of care on admission were excluded.

Results

A total of 639 consecutive patients (supportive care, n = 247; treatment n = 392) were included in the analysis. Overall, the 28-day mortality rate was 12.2%. The mortality was 8.7% higher in the treatment group (15.6% vs 6.9% in the supportive care group, P < 0.001). Treatment was not protective against progression to severe disease (18.4% vs 3.6% with supportive care, P < 0.0001). Time to defervescence, duration of oxygen support, and hospital and intensive care unit (ICU) length of stay were also higher in the treatment group. In multivariate analysis, 60 years or older, presence of severe disease, and need for ICU admission were identified as independent predictors of 28-day mortality. There were 41 (10.5%) adverse event in the treatment group, with the majority being QT prolongation and gastrointestinal effects.

Conclusions

In this cohort of hospitalized patients admitted to acute care services, treatment with hydroxychloroquine, lopinavir/ritonavir or both could not be shown to improve mortality, progression to severe disease, or clinical response.
Developing clinical prediction models for nonrecovery in older patients seeking care for back pain: the back complaints in the elders prospective cohort study
Authors: van der Gaag Wendelien H. , Chiarotto Alessandro , Heymans Martijn W. , Enthoven Wendy T.M. , van Rijckevorsel-Scheele Jantine , Bierma-Zeinstra Sita M.A. , Bohnen Arthur M. , Koes Bart W.
Published: December 2020

Back pain is a leading cause of disability worldwide and is common in older adults. No clinical prediction models for poor long-term outcomes have been developed in older patients with back pain. This study aimed to develop and internally validate 3 clinical prediction models for nonrecovery in this population. A prospective cohort study in general practice was conducted (Back Complaints in the Elders, Netherlands), including 675 patients >55 years with a new episode of care for back pain. Three definitions of nonrecovery were used combining 6-month and 12-month follow-up data: (1) persistent back pain, (2) persistent disability, and (3) perceived nonrecovery. Sample size calculation resulted in a maximum of 14 candidate predictors that were selected from back pain prognostic literature and clinical experience. Multivariable logistic regression was used to develop the models (backward selection procedure). Models' performance was evaluated with explained variance (Nagelkerke's R2), calibration (Hosmer–Lemeshow test), and discrimination (area under the curve [AUC]) measures. The models were internally validated in 250 bootstrapped samples to correct for overoptimism. All 3 models displayed good overall performance during development and internal validation (ie, R2 > 30%; AUC > 0.77). The model predicting persistent disability performed best, showing good calibration, discrimination (AUC 0.86, 95% confidence interval 0.83-0.89; optimism-adjusted AUC 0.85), and explained variance (R2 49%, optimism-adjusted R2 46%). Common predictors in all models were: age, chronic duration, disability, a recent back pain episode, and patients' recovery expectations. Spinal morning stiffness and pain during spinal rotation were included in 2 of 3 models. These models should be externally validated before being used in a clinical primary care setting.
Technical Report: A New Device Attached to a Smartphone for Objective Vision Screening
Authors: Wang Guang-Ji , Wang John Y. , Scott Clifford , Qu Jia , Lu Fan , Rio David , Purcell Howard , Chen Jie
Published: December 2020

SIGNIFICANCE

A new device attached to a smartphone was created for objective vision screening of young children including infants and newborns. The device is compact, lightweight, portable, cost-effective, and easy to operate. Therefore, it is suitable for screening large numbers of children in clinical settings, schools, and communities.

PURPOSE

This article introduces a new device attached to a smartphone for objective vision screening. It can detect and categorize significant refractive errors, anisometropia, strabismus, cloudy ocular media, and ptosis that may cause amblyopia.

METHODS

The new device applies the same principles as conventional streak retinoscopy but examines both eyes simultaneously and records the results electronically. The device comprises optical elements that produce a precise streak light beam and move it across a child's both eyes. The smartphone's video camera catches and records the motion of retinal reflex inside the child's pupils. By observing the direction of motion of the retinal reflex relative to the light beam motion, as well as its speed, width, and brightness, the examiner is able to assess the individual and comparative refractive status, ocular alignment, and other conditions.

RESULTS

Vision screening with this device does not require any subjective response from children. The examination can be performed and analyzed by nonprofessionals after a short learning period of time. Because the examination results are electronically recorded by the smartphone, they can be stored in the child's files and sent out for professional consultations.

CONCLUSIONS

The new device will provide the same functions as conventional streak retinoscopy but examines a child's both eyes simultaneously, so that, in addition to categorizing refractive errors and assessing clarity of refractive media of the eyes, it can also detect anisometropia, strabismus, and anisocoria. In addition to showing the examination results on the smartphone's screen, the device can also store the results electronically.
In Vivo Human Corneal Shear-wave Optical Coherence Elastography
Authors: Lan Gongpu , Aglyamov Salavat R. , Larin Kirill V. , Twa Michael D.
Published: December 2020

SIGNIFICANCE

A novel imaging technology, dynamic optical coherence elastography (OCE), was adapted for clinical noninvasive measurements of corneal biomechanics.

PURPOSE

Determining corneal biomechanical properties is a long-standing challenge. Elasticity imaging methods have recently been developed and applied for clinical evaluation of soft tissues in cancer detection, atherosclerotic plaque evaluation, surgical guidance, and more. Here, we describe the use of dynamic OCE to characterize mechanical wave propagation in the human cornea in vivo, thus providing a method for clinical determination of corneal biomechanical properties.

METHODS

High-resolution phase-sensitive optical coherence tomography imaging was combined with microliter air-pulse tissue stimulation to perform dynamic elasticity measurements in 18 eyes of nine participants. Low-pressure (0.1 mmHg), spatiotemporally discreet (150 μm, 800 μs) tissue stimulation produced submicron-scale tissue deformations that were measured at multiple positions over a 1-mm2 area. Surface wave velocity was measured and used to determine tissue stiffness. Elastic wave propagation velocity was measured and evaluated as a function of IOP and central corneal thickness.

RESULTS

Submicron corneal surface displacement amplitude (range, 0.005 to 0.5 μm) responses were measured with high sensitivity (0.24 nm). Corneal elastic wave velocity ranged from 2.4 to 4.2 m/s (mean, 3.5; 95% confidence interval, 3.2 to 3.8 m/s) and was correlated with central corneal thickness (r = 0.64, P < .001) and IOP (r = 0.52, P = .02).

CONCLUSIONS

Phase-sensitive optical coherence tomography imaging combined with microliter air-pulse mechanical tissue stimulation has sufficient detection sensitivity to observe submicron elastic wave propagation in corneal tissue. These measurements enable in vivo corneal stiffness determinations that will be further studied for use with disease detection and for monitoring clinical interventions.
Speckle tracking echocardiographic assessment of left ventricular longitudinal strain in female patients with subclinical hyperthyroidism
Authors: Abdelrazk Randa R. , El-Sehrawy Amr A. , Ghoniem Mohamed G. M. , Amer Maged Z.
Published: December 2020

Background

Patients with subclinical hypothyroidism (SCH) are subjected to many cardiac changes. However, these changes are of gradual onset and cannot be usually detected using conventional diagnostic methods. Speckle tracking echocardiography (STE) is capable to detect cardiac function alterations usually unidentified by conventional echocardiography. The present study aimed to evaluate the role of STE in the detection of early cardiac changes in female patients with SCH.

Methods

The study included 33 female patients with SCH and 30 matched healthy volunteer women with normal thyroid functions who served as controls. Upon recruitment, all participants were subjected to careful history taking, thorough clinical examination and routine laboratory investigations, including thyroid-stimulating hormone and Free T4. The echocardiographic examination included conventional, color Doppler and two-dimensional STE.

Results

Analysis of conventional echocardiographic data revealed that patients had significantly higher end-systolic volume when compared with controls. In addition, it was noted that SCH patients had significantly lower mitral E/A ratio, isovolumetric relaxation time and significantly higher left atrium volume index in comparison to controls. In respect to STE data, we noted that patients had significantly lower values of mid-anteroseptal, apical lateral, apical septal, apical apex, AP4L strain and global strain % when compared with controls.

Conclusions

Patients with SCH have deteriorated global strain in comparison to healthy controls.
CKS1-dependent proteostatic regulation has dual roles combating acute myeloid leukemia whilst protecting normal hematopoiesis
Authors: Grey W. , Rio-Machin A. , Casado-Izquierdo P. , Miettinen J.J. , Copley F. , Parsons A. , Heckman C.A. , Cutillas P. , Gribben J. , Fitzgibbon J. , Bonnet D.
Published: December 2020

Acute myeloid leukemia (AML) is an aggressive hematological disorder comprising a hierarchy of quiescent leukemic stem cells (LSCs) and proliferating blasts with limited self-renewal ability. AML has a dismal prognosis, with extremely low two-year survival rates in the poorest cytogenetic risk patients, primarily due to the failure of intensive chemotherapy protocols unable to deplete LSCs, which reconstitute the diseasein vivo, and the significant toxicity towards healthy hematopoietic cells. Whilst much work has been done to identify genetic and epigenetic vulnerabilities in AML LSCs, little is known about protein dynamics and the role of protein degradation in drug resistance and relapse. Here, using a highly specific inhibitor of the SCFSKP2-CKS1complex, we report a dual role for CKS1-dependent protein degradation in reducing AML blastsin vivo, and importantly depleting LSCs. Whilst many AML LSC targeted therapies show significant toxicity to healthy hematopoiesis, inhibition of CKS1-dependent protein degradation has the opposite effect, protecting normal hematopoietic cells from chemotherapeutic toxicity. Together these findings demonstrate CKS1-dependent proteostasis is key for normal and malignant hematopoiesis.

Significance

CKS1-dependent protein degradation is a specific vulnerability in AML LSCs. Specific inhibition of SCFSKP2-CKS1is lethal toCKS1BhighAML blasts and all AML LSCs. Normal hematopoiesis is protected from chemotherapeutic toxicity by inhibition of CKS1-dependent protein degradation, substantiating a dual role for CKS1-dependent protein degradation in clinical treatment of AML.
Novel insights into the mode of action of 1,4-dioxane using a systems screening approach
Authors: Charkoftaki Georgia , Golla Jaya Prakash , Santos-Neto Alvaro , Orlicky David J. , Garcia-Milian Rolando , Chen Ying , Rattray Nicholas J.W. , Cai Yuping , Wang Yewei , Shern Colin T , Mironova Varvara , Wang Yensheng , Johnson Caroline H. , Thompson David C. , Vasiliou Vasilis
Published: December 2020

1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States (US). While it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, female BDF-1 mice were exposed to 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one or four weeks, to explore the toxic effects. Histopathological studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Immunohistochemical analysis of the liver revealed increased H2AXγ-positive hepatocytes (a marker of DNA double strand breaks), and an expansion of precholangiocytes (reflecting both DNA damage and repair mechanisms) after exposure. Liver transcriptomics revealed 1,4-DX-induced perturbations in signaling pathways predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, feces and urine metabolomic profiling revealed no effect of 1,4-DX exposure, and bile acid quantification in liver and feces similarly showed no effect of exposure. We speculate that the results may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death but have activated the repair systems in response to 1,4-DX exposure.
Feeding intervention potentiates the effect of mechanical loading to induce new bone formation in mice
Authors: Samvelyan Hasmik Jasmine , Mathers John Cummings , Skerry Timothy Michael
Published: December 2020

The benefits of increased human lifespan depend upon duration of healthy, independent living; the healthspan. Bone-wasting disorders contribute significantly to loss of independence, frailty and morbidity in older people. Therefore, there is an unmet need globally for lifestyle interventions to reduce the likelihood of bone fractures with age. Although many mechanisms are involved in disorders of bone loss, there is no single regulatory pathway and, therefore, there is no single treatment available to prevent their occurrence. Our aim in these studies was to determine whether fasting/feeding interventions alter the effect of mechanical loading on bone anabolic activities and increase bone mass. In young 17-week-old mice, 16-hour fasting period followed by reintroduction of food for 2 hours increased markedly the potency of mechanical loading, that mimics the effect of exercise, to induce new cortical bone formation. Consistent with this finding, fasting and re-feeding increased the response of bone to a loading stimulus that, alone, does not stimulate new bone formation in ad-lib fed mice. Older mice (20-months) experienced no potentiation of loading-induced bone formation with the same timing of feeding interventions. Interestingly, the pre-, prandial and postprandial endocrine responses in older mice were different from those in young animals. The hormones that change in response to timing of feeding have osteogenic effects that interact with loading-mediated effects. Our findings indicate associations between timing of food ingestion and bone adaptation to loading. If translated to humans, such non-pharmacological lifestyle interventions may benefit skeletal health of humans throughout life-course and in older age.
Attentionally modulated subjective images reconstructed from brain activity
Authors: Horikawa Tomoyasu , Kamitani Yukiyasu
Published: December 2020

Visual image reconstruction from brain activity produces images whose features are consistent with the neural representations in the visual cortex given arbitrary visual instances [1–3], presumably reflecting the person’s visual experience. Previous reconstruction studies have been concerned either with how stimulus images are faithfully reconstructed or with whether mentally imagined contents can be reconstructed in the absence of external stimuli. However, many lines of vision research have demonstrated that even stimulus perception is shaped both by stimulus-induced processes and top-down processes. In particular, attention (or the lack of it) is known to profoundly affect visual experience [4–8] and brain activity [9–21]. Here, to investigate how top-down attention impacts the neural representation of visual images and the reconstructions, we use a state-of-the-art method (deep image reconstruction [3]) to reconstruct visual images from fMRI activity measured while subjects attend to one of two images superimposed with equally weighted contrasts. Deep image reconstruction exploits the hierarchical correspondence between the brain and a deep neural network (DNN) to translate (decode) brain activity into DNN features of multiple layers, and then create images that are consistent with the decoded DNN features [3, 22, 23]. Using the deep image reconstruction model trained on fMRI responses to single natural images, we decode brain activity during the attention trials. Behavioral evaluations show that the reconstructions resemble the attended rather than the unattended images. The reconstructions can be modeled by superimposed images with contrasts biased to the attended one, which are comparable to the appearance of the stimuli under attention measured in a separate session. Attentional modulations are found in a broad range of hierarchical visual representations and mirror the brain–DNN correspondence. Our results demonstrate that top-down attention counters stimulus-induced responses and modulate neural representations to render reconstructions in accordance with subjective appearance. The reconstructions appear to reflect the content of visual experience and volitional control, opening a new possibility of brain-based communication and creation.
Conflict-mediated tasks for studying the act of facing threats in pursuit of rewards
Authors: Illescas-Huerta Elizabeth , Ramirez-Lugo Leticia , Sierra Rodrigo Ordonez , Quillfeldt Jorge A. , Sotres-Bayon Francisco
Published: December 2020

Survival depends on the ability of animals to avoid threats and approach rewards. Traditionally, these two opposing motivational systems have been studied separately. In nature, however, they regularly occur simultaneously. When threat- and reward-eliciting stimuli (learned or unlearned) co-occur, a motivational conflict emerges that challenges individuals to weigh available options and execute a single behavioral response (avoid or approach). Previous animal models using approach-avoidance conflicts have often focused on the ability to avoid threats by forgoing the opportunity to obtain rewards. In contrast, behavioral tasks designed to capitalize on the ability to actively choose to execute approach behaviors despite threats are lacking. Thus, we developed three conflict-mediated tasks to directly study rats confronting threats to obtain rewards guided by innate and conditioned cues. One conflict task involves crossing a potentially electrified grid to obtain food on the opposite end of a straight alley, the second task is based on the step-down threat avoidance paradigm, and the third one is a modified version of the open field test. We used diazepam to pharmacologically validate conflict-mediated behaviors in our tasks. We found that, regardless of whether competing stimuli were conditioned or innate, a low diazepam dose facilitated taking action to obtain rewards in the face of threats during conflict, without affecting choice behavior when there was no conflict involved. Using this validated set of innate/learned conflict-mediated tasks could help understand the underlying brain mechanisms that allow animals to confront threats, by actively suppressing defensive responses, to achieve goals.
SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity
Authors: Alvarez Carlos Ramirez , Sharma Ashwini Kumar , Kee Carmon , Thomas Leonie , Boulant Steeve , Herrmann Carl
Published: December 2020

COVID-19 outbreak is the biggest threat to human health in recent history. Currently, there are over 1.5 million related deaths and 75 million people infected around the world (as of 22/12/2020). The identification of virulence factors which determine disease susceptibility and severity in different cell types remains an essential challenge. The serine proteaseTMPRSS2has been shown to be important for S protein priming and viral entry, however, little is known about its regulation.SPINT2is a member of the family of Kunitz type serine protease inhibitors and has been shown to inhibitTMPRSS2. Here, we explored the existence of a co-regulation betweenSPINT2/TMPRSS2and found a tightly regulated protease/inhibitor expression balance across tissues. We found thatSPINT2negatively correlates with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines and was down-regulated in secretory cells from COVID-19 patients. We validated our findings using Calu-3 cell lines and observed a strong increase in viral load afterSPINT2knockdown. Additionally, we evaluated the expression ofSPINT2in datasets from comorbid diseases using bulk and scRNA-seq data. We observed its down-regulation in colon, kidney and liver tumors as well as in alpha pancreatic islets cells from diabetes Type 2 patients, which could have implications for the observed comorbidities in COVID-19 patients suffering from chronic diseases.