bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonfunctional extradural thoracic spine paraganglioma in a pediatric patient: a case report
Authors: Alshaya Weal , Aleissa Sami I , Abdulfaraj Muath I , Aldeghaither Sarah A , Alhandi Ali A
Published: August 2020

Paraganglioma in the spine remains a rare occurrence that is mostly benign and commonly associated with other inherited symptoms. Presentation in the pediatric population is rare with a high risk of recurrence. This case reports an unusual presentation of a slowly progressing nonfunctional thoracic paraganglioma in a 6-year-old female child that presented with mass-related symptoms sparing the spinal canal. Tumor recurred after initial video-assisted thoracoscopic surgery excision with significant involvement of the thoracic spinal canal. Patient underwent a second surgery utilizing a posterior approach and laminectomies. Succinate dehydrogenase-B gene association was confirmed through molecular testing afterward. Such tumors can be malignant with 7% present with distant metastasis. Image-based differentiation of malignant tumors remains difficult, adding to the urgency in diagnosing these tumors. Furthermore, the unlikely age presentation compounds to the challenges of the diagnostic process.x The patient remains tumor free 12 months postoperatively.
A Preliminary Investigation on the Effects of Atenolol for Treating Symptoms of Anxiety
Authors: Armstrong Cody , Kapolowicz Michelle R
Published: July 2020

Introduction

Anxiety disorders are among the most commonly diagnosed of psychiatric disorders. Many symptoms of posttraumatic stress disorder are also anxiety-related. Traditional medications used to treat these disorders, such as antidepressants and benzodiazepines, are often ineffective, not well-tolerated, and can be habit forming. An alternative agent is, therefore, needed. Beta-blockers are one class of medication with potential to treat anxiety-related disorders; however, current evidence remains limited and requires further characterization. To this end, this retrospective study aims to present a novel preliminary report on the use of the beta-blocker, atenolol, to potentially treat anxiety-related disorders.

Materials and methods

Ninety-two patients were identified from outpatient military mental health clinics in Okinawa, Japan, who had received atenolol for mental health-related symptoms. Primary measures collected were the rates of patient-reported (1) general beneficial/positive effect of atenolol, (2) adverse effects from atenolol, and (3) preference of atenolol to propranolol. Data were collected from patients who were given binary response options to report their perceived experiences for each primary measure. This study was approved by the Naval Medical Center San Diego Institutional Review Board.

Results

The results showed 86% of patients reporting a positive effect and continuing to take atenolol, including 87% with a diagnosis of posttraumatic stress disorder, 100% with diagnosis of other specified trauma- and stressor-related disorder, and 81% diagnosed with anxiety disorders. In total, 90% of patients denied adverse effects or found the adverse effects tolerable. Additionally, 100% of patients who had previously taken propranolol for anxiety reported that they preferred atenolol.

Conclusions

The present preliminary observational data suggests that atenolol may be well-tolerated and effective among persons with anxiety disorders. These data also suggest that atenolol may be more effective and better tolerated than propranolol, which is the most commonly prescribed beta-blocker for these conditions; however, more rigorously controlled empirical studies are needed to further substantiate this claim. Despite an overwhelmingly high rate of positive reports from patients’ self-evaluations of atenolol treatment for anxiety-related disorders, this early investigation was not placebo-controlled nor double-blinded, and formal outcome measures were not assessed due to a lack of availability. More detailed examinations are needed to further determine whether atenolol is a viable alternative or augmenting agent to propranolol, benzodiazepines, and antidepressants for anxiety disorders and trauma-related disorders.
Unveiling cloudy exoplanets: the influence of cloud model choices on retrieval solutions
Authors: Barstow Joanna K
Published: August 2020

In recent years, it has become clear that a substantial fraction of transiting exoplanets have some form of aerosol present in their atmospheres. Transit spectroscopy – mostly of hot Jupiters, but also of some smaller planets – has provided evidence for this, in the form of steep downward slopes from blue to red in the optical part of the spectrum, and muted gas absorption features throughout. Retrieval studies seeking to constrain the composition of exoplanet atmospheres must therefore account for the presence of aerosols. However, clouds and hazes are complex physical phenomena, and the transit spectra that are currently available allow us to constrain only some of their properties. Therefore, representation of aerosols in retrieval models requires that they are described by only a few parameters, and this has been done in a variety of ways within the literature. Here, I investigate a range of parametrizations for exoplanet aerosol and their effects on retrievals from transmission spectra of hot Jupiters HD 189733b and HD 209458b. I find that results qualitatively agree for the cloud/haze itself regardless of the parametrization used, and indeed using multiple approaches provides a more holistic picture; the retrieved abundance of H2O is also very robust to assumptions about aerosols. I also find strong evidence that aerosol on HD 209458b covers less than half of the terminator region, whilst the picture is less clear for HD 189733b.
Fast synthetic spectral fitting for large stellar samples: a critical test with 25 bright stars of known rotation
Authors: Schröder K-P , Mittag M , Flor Torres L M , Jack D , Snellen I
Published: August 2020

This work presents and tests a reliable, but nonetheless fast, method for determining the physical parameters of large stellar samples with moderate-resolution spectra, with extensive host star–exoplanet studies in mind. The proposed strategy complements spectral synthesis for obtaining spectroscopically sensitive parameters (i.e. effective temperature and rotation velocity) through other data to keep less critical quantities fixed. We test this approach on a sample of 25 bright (4–7 mag), cool main-sequence stars, for which rotation periods are known from chromospheric activity monitoring. On the basis of good-quality (signal-to-noise ratio 70–80) Tracking and Imaging Gamma-Ray Experiment–Heidelberg Extended Range Optical Spectrograph (TIGRE–HEROS) spectra with a modest spectral resolving power of R = 21 000, we employ the fast iSpec tool. With gravities calculated and approximate metallicities taken from uvby photometry (Geneva–Copenhagen catalogue), spectral synthesis is focused on refining the crucial effective temperature. Finally, rotational velocities are fitted. However, these suffer from cross-talk with gravity and convective turbulence. We find that prescribing macroscopic turbulent velocities for most stars within 2–3 km s−1 (with 4–6 km s−1 for only our three warmest stars) and microscopic turbulent velocities within 0.7–1.5 km s−1 (turbulence increasing with effective temperature, from under 5000 K to 6300 K) results in a satisfactory match (with residuals of 2.5 km s−1) of the period-related, very small rotation velocities of our sample stars. With this prescription, the fast spectral synthesis method described yields effective temperatures similar to intensive atmospheric modelling of high-resolution spectra.
Optimal periodicity searching: revisiting the fast folding algorithm for large-scale pulsar surveys
Authors: Morello V , Barr E D , Stappers B W , Keane E F , Lyne A G
Published: August 2020

The fast folding algorithm (FFA) is a phase-coherent search technique for periodic signals. It has rarely been used in radio pulsar searches, having been historically supplanted by the less computationally expensive fast fourier transform (FFT) with incoherent harmonic summing (IHS). Here, we derive from first principles that an FFA search closely approaches the theoretical optimum sensitivity to all periodic signals; it is analytically shown to be significantly more sensitive than the standard FFT+IHS method, regardless of pulse period and duty cycle. A portion of the pulsar phase space has thus been systematically underexplored for decades; pulsar surveys aiming to fully sample the pulsar population should include an FFA search as part of their data analysis. We have developed an FFA software package, riptide, fast enough to process radio observations on a large scale; riptide has already discovered sources undetectable using existing FFT+IHS implementations. Our sensitivity comparison between search techniques also shows that a more realistic radiometer equation is needed, which includes an additional term: the search efficiency. We derive the theoretical efficiencies of both the FFA and the FFT+IHS methods and discuss how excluding this term has consequences for pulsar population synthesis studies.
Uncoupling gene expression noise along the central dogma using genome engineered human cell lines
Authors: Quarton Tyler , Kang Taek , Papakis Vasileios , Nguyen Khai , Nowak Chance , Li Yi , Bleris Leonidas
Published: August 2020

Eukaryotic protein synthesis is an inherently stochastic process. This stochasticity stems not only from variations in cell content between cells but also from thermodynamic fluctuations in a single cell. Ultimately, these inherently stochastic processes manifest as noise in gene expression, where even genetically identical cells in the same environment exhibit variation in their protein abundances. In order to elucidate the underlying sources that contribute to gene expression noise, we quantify the contribution of each step within the process of protein synthesis along the central dogma. We uncouple gene expression at the transcriptional, translational, and post-translational level using custom engineered circuits stably integrated in human cells using CRISPR. We provide a generalized framework to approximate intrinsic and extrinsic noise in a population of cells expressing an unbalanced two-reporter system. Our decomposition shows that the majority of intrinsic fluctuations stem from transcription and that coupling the two genes along the central dogma forces the fluctuations to propagate and accumulate along the same path, resulting in increased observed global correlation between the products.
Management of Thoracic Disc Herniation Using the Mini-Open Retropleural Approach: Technique Illustration and Clinical Outcomes of 33 Patients From a Single Academic Center
Authors: Noureldine Mohammad Hassan A , Pressman Elliot , Krafft Paul R , Molcanyi Marek , Tran Nam D , Greenberg Mark S , Alikhani Puya
Published: August 2020

BACKGROUND

Conventional surgical approaches used in the management of thoracic disc herniation (TDH) are associated with high morbidity. The development of minimally invasive and mini-open approaches has consistently improved patient outcomes.

OBJECTIVE

To report our experience and outcomes of patients with symptomatic TDHs who underwent discectomy and partial corpectomy using the mini-open retropleural (MORP) approach as well as provide a detailed and illustrated technical description of the approach.

METHODS

Retrospective chart review was performed on all patients with symptomatic TDHs who underwent a MORP approach at a tertiary academic center between 2011 and 2019. Patient demographic, clinical, and imaging data were examined (n = 33). The surgical technique is illustrated and described in detail.

RESULTS

Discectomy of the herniated thoracic discs was successfully achieved in all patients using the MORP approach. Calcified discs were present in 63.6% (n = 21) of patients. Immediate instrumentation and fusion were performed in 30.3% (n = 10) of patients, which were among the earlier cases in this series. Symptomatic pleural effusions and cerebrospinal fluid leakage occurred in 6.1% (n = 2) and 9.1% (n = 3), respectively. No patient required chest tube placement.

CONCLUSION

The MORP approach described in this manuscript is feasible and safe in achieving discectomy in patients with symptomatic TDHs. Compared to conventional open and other minimally invasive approaches, patients undergoing the MORP approach may have better outcomes with lower complication rates.
Cholera outbreak investigation, Bhadola, Delhi, India, April–May 2018
Authors: Singh Akhileshwar , Gupta Rakesh , Dikid Tanzin , Saroha Ekta , Sharma Naresh Chand , Sagar Sanjay , Gupta Sudha , Bindra Suneet , Khasnobis Pradeep , Jain Sudhir Kumar , Singh Sujeet
Published: August 2020

Background

In the Gangetic plains of India, including Delhi, cholera is endemic. On 10 May 2018, staff at the north Delhi district surveillance unit identified a laboratory-confirmed cholera outbreak when five people tested positive for Vibrio cholerae O1 Ogawa serotype in Bhadola. We investigated to identify risk factors and recommend prevention measures.

Methods

We defined a case as ≥3 loose stools within 24 h in a Bhadola resident during 1 April–29 May 2018. We searched for cases house-to-house. In a 1 : 1 unmatched case control study, a control was defined as an absence of loose stools in a Bhadola resident during 1 April–29 May 2018. We selected cases and controls randomly. We tested stool samples for Vibrio cholerae by culture. We tested drinking water for fecal contamination. Using multivariable logistic regression we calculated adjusted ORs (aORs) with 95% CIs.

Results

We identified 129 cases; the median age was 14.5 y, 52% were females, 27% were hospitalized and there were no deaths. Symptoms were abdominal pain (54%), vomiting (44%) and fever (29%). Among 90 cases and controls, the odds of illness were higher for drinking untreated municipal water (aOR=2.3; 95% CI 1.0 to 6.2) and not knowing about diarrhea transmission (aOR=4.9; 95% CI 1.0 to 21.1). Of 12 stool samples, 6 (50%) tested positive for Vibrio cholerae O1 Ogawa serotype. Of 15 water samples, 8 (53%) showed growth of fecal coliforms.

Conclusions

This laboratory-confirmed cholera outbreak associated with drinking untreated municipal water and lack of knowledge of diarrhea transmission triggered public health action in Bhadola, Delhi.
Breast Cancer in Patients Younger Than 40 Years: Imaging, Assessment, and Management
Authors: Suleimenova Danara , Eghtedari Mohammad , Rakow-Penner Rebecca , Lim Vivian , Ladd William , Ojeda-Fournier Haydee
Published: July 2020

“Young women,” defined as women younger than 40 years at breast cancer diagnosis, represent approximately 7% of all women diagnosed with breast cancer in developed countries. Breast cancer is the leading cause of cancer-related death in young women. It constitutes more than 12,150 newly diagnosed patients every year in the United States. Young women have specific issues including those related to fertility, cancer genetics, and psychosocial concerns, and often need a different approach than do older women.1 Although breast cancer in older women is detected most commonly by mammographic screening, breast cancer in young women is diagnosed more often by clinical symptoms. Delayed diagnosis in this age group is common due to lack of awareness in women and physicians.2 The radiologist must have an appropriate level of suspicion while evaluating young women so as not to miss breast cancer.
Evaluation of Coronavirus Disease 2019 Severity Using Urine Biomarkers
Authors: Katagiri Daisuke , Ishikane Masahiro , Asai Yusuke , Kinoshita Noriko , Ota Masayuki , Moriyama Yuki , Ide Satoshi , Nakamura Keiji , Nakamoto Takato , Nomoto Hidetoshi , Akiyama Yutaro , Miyazato Yusuke , Suzuki Tetsuya , Okuhama Ayako , Kanda Kohei , Wakimoto Yuji , Morioka Shinichiro , Saito Sho , Yamamoto Kei , Ujiie Mugen , Hayakawa Kayoko , Kustuna Satoshi , Yanagawa Yasuaki , Terada Junko , Takasaki Jin , Izumi Shinyu , Hojo Masayuki , Hinoshita Fumihiko , Sugiyama Masaya , Noiri Eisei , Mizokami Masashi , Ohmagari Norio , Sugiyama Haruhito
Published: August 2020

Subjects:

Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019.

Interventions:

Not applicable.

Measurements and Main Results:

This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary β2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low β2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were β2-microglobulin; severe versus moderate + mild: 2,457 μg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 μg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary β2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend.

Conclusions:

Evaluating urinary biomarkers such as β2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.
Preparedness and Reorganization of Care for Coronavirus Disease 2019 Patients in a Swiss ICU: Characteristics and Outcomes of 129 Patients
Authors: Primmaz Steve , Le Terrier Christophe , Suh Noémie , Ventura François , Boroli Filippo , Bendjelid Karim , Cereghetti Sara , Giraud Raphaël , Heidegger Claudia , Pugin Deborah , Siegenthaler Nils , Tassaux Didier , Cabrol Jean-Clément , Dolet Nathan , Ellenberger Christoph , Keli Barcelos Gleicy , Licker Marc-Joseph , Savoldelli Georges , Schiffer Eduardo , Gayet-Ageron Angèle , Kaiser Laurent , Tramèr Martin R. , Pugin Jérôme
Published: July 2020

Objectives:

In many countries, large numbers of critically ill patients with coronavirus disease 2019 are admitted to the ICUs within a short period of time, overwhelming usual care capacities. Preparedness and reorganization ahead of the wave to increase ICU surge capacity may be associated with favorable outcome. The purpose of this study was to report our experience in terms of ICU organization and anticipation, as well as reporting patient characteristics, treatment, and outcomes.

Design:

A prospective observational study.

Setting:

The division of intensive care at the Geneva University Hospitals (Geneva, Switzerland).

Patients:

All consecutive adult patients with acute respiratory failure due to coronavirus disease 2019 admitted in the ICU between March 9, 2020, and May 19, 2020, were enrolled. Patients’ demographic data, comorbidities, laboratory values, treatments, and clinical outcomes were collected.

Interventions:

None.

Measurements and Main Results:

The ICU was reorganized into cells of six to eight patients under the care of three physicians and five nurses. Its capacity increased from 30 to 110 beds, fully equipped and staffed, transforming the surgical intermediate care unit, the postoperative care facility, and operating theaters into ICUs. Surge capacity has always exceeded the number of patients hospitalized. Among 129 critically ill patients with severe acute hypoxemic respiratory failure, 96% required invasive mechanical ventilation. A total of 105 patients (81%) were discharged alive and 24 died, corresponding to a mortality of 19%. Patients who died were significantly older, with higher severity scores at admission, had higher levels of d-dimers, plasma creatinine, high-sensitive troponin T, C-reactive protein, and procalcitonin, and required more frequent prone sessions.

Conclusions:

A rapid increase in ICU bed capacity, including adequate equipment and staffing, allowed for a large number of critically ill coronavirus disease 2019 patients to be taken care of within a short period of time. Anticipation and preparedness ahead of the wave may account for the low mortality observed in our center. These results highlight the importance of resources management strategy in the context of the ongoing coronavirus disease 2019 pandemic.
Tissue sodium content in hypertension and related organ damage
Authors: Kolwelter Julie , Uder Michael , Schmieder Roland E.
Published: August 2020

Most textbooks state that sodium (Na) accumulation goes hand in hand with fluid retention to maintain the environmental isotonicity. In the last century, several studies found, however, that Na is stored in the extravascular space leading to an activation of the monocyte phagocytic system cells that work as a regulator of the interstitial electrolyte homeostasis. 23Na-MRI was developed to quantify noninvasively, accurately and reliably tissue Na content. In this review, we give an up-to-date overview of clinical studies utilizing this 23Na-MRI technique to elucidate the importance of tissue Na content in patients with cardiovascular risk factors leading to microvascular and macrovascular complications. Na storage leads ultimately to organ damage such as left ventricular hypertrophy or hypertrophic vascular remodeling of resistance vessels. Elevated Na content in muscle and skin has been detected in patients with treatment resistant hypertension, type 2 diabetes mellitus, acute and chronic heart failure, chronic kidney disease and end-stage renal failure. Pharmacological interventions have shown that a mobilization of extracellular accumulated Na is possible and may emerge as a new therapeutic approach in some diseases.
Comparison of Flexible 3D Printed Stenotic Airway Model Versus Standard Model for Therapeutic Bronchoscopy Training a Proof of Concept
Authors: Chee Alex , Sierra-Ruiz Melibea , Parikh Mihir S. , Majid Adnan
Published: July 2020

Aim:

This study aimed to determine operator impressions of an airway obstruction procedure using a custom silicone model of low cost and high accuracy.

Background:

Current procedural education for therapeutic bronchoscopy relies on animal models, supervised in-patient training, and inanimate artificial models. Model manufacturing via lost-wax casting allows for the flexibility of the material selection and reproduction of complex airway shapes.

Methods:

A patient computed tomography scan was anonymized and segmented into a stereolithographic (STL) file. The water dissolvable interior airway mold was 3-dimensional (D) printed using polyvinyl alcohol and the exterior mold was printed with polylactic acid. Flexible silicone was injected into the mold. During advanced bronchoscopy courses (2017-2018) at Beth Israel Deaconess Medical Center, participants were asked to evaluate both standard bronchoscopy manikin and the manikin with 3D customization.

Results:

We evaluated 17 participants with different levels in training in the pulmonary field. All of them reported that they previously have performed >100 bronchoscopies, 88% having treated patients with airway stenosis. In total, 77% of participants thought the 3D model was better or much better for airway inspection when compared with Broncho-Boy. Overall, 94% of participants reported the 3D model was accurate or very accurate for realism. In total, 69% of trainees reported the overall experience as excellent. All of them reported 3D model would improve their skills on stent placement.

Conclusion:

3D printing with silicone lost wax casting can be used to reproduce airway abnormalities for tactile simulation bronchoscopy. Reproducible custom airway models can be created for a relatively low cost.
Quality of Life in Parents of Children With Biliary Atresia
Authors: Rodijk Lyan H. , Schins Eke M.W. , Witvliet Marieke J. , Alizadeh Behrooz Z. , Verkade Henkjan J. , de Kleine Ruben H. , Hulscher Jan B.F. , Bruggink Janneke L.M.
Published: August 2020

Objectives:

The aim of the study was to determine quality of life (QoL), stress, and anxiety levels in parents of children with biliary atresia (BA), and to assess factors associated with parental QoL.

Methods:

Parents of children (6–16 years) with BA were included in this cross-sectional study. We used validated questionnaires to assess parental QoL, stress, and anxiety levels. We compared the results with reference data from the general population and determined associated factors using generalized linear mixed model analysis. Results are given as mean ± SD or median [min-max].

Results:

We included 61 parents of 39 children (aged 11 ± 3 years). Thirty-one children (79%) had undergone a liver transplantation (LTx). Parents reported reduced family activities (88 [8–100] vs 95 [30–100], P = 0.002) and more emotional worry (83 [17–100] vs 92 [95–100], P < 0.001) compared with reference data, but a stronger family cohesion (85 [30–100] vs 60 [30–100], P = 0.05). Scores on parental QoL, anxiety and stress were similar to reference data. Fathers (16.0 [11–19]) and mothers (15.4 ± 1.4) scored higher on the psychological domain compared with reference data (vs 14.7 ± 2.2, P < 0.01). There was no significant difference in QoL of parents with children with native liver or those who had undergone LTx. Older age and high anxiety trait in parents were adversely associated with physical QoL. Household income below €35 000/year and high anxiety trait were adversely associated with environmental QoL.

Conclusions:

QoL in parents of school-aged children with BA appears to be unaffected. Parents with high-anxiety personality trait, older age, and low household income are at increased risk of impaired QoL.
Case Report: Presumed Optic Neuropathy after Amiodarone and then Dronedarone for Treatment of Atrial Fibrillation
Authors: Maharshak Idit , Paul Michael , Steiner Hillel
Published: August 2020

SIGNIFICANCE

Amiodarone and dronedarone have recognized ophthalmological adverse effects including optic neuropathy. The recognition of optic neuropathy as a complication of amiodarone and dronedarone treatment may enable withdrawing the drug and accordingly preventing permanent vision loss.

PURPOSE

This study aimed to describe a case of optic neuropathy after substitution of amiodarone with dronedarone for treatment of atrial fibrillation.

CASE REPORT

An 81-year-old man treated with dronedarone for atrial fibrillation after amiodarone had caused tremor developed sequential permanent vision loss in both eyes.

CONCLUSIONS

The importance of timely recognition of optic neuropathy as a complication of amiodarone and dronedarone treatment may enable discontinuing the drug, thus preventing permanent vision loss.
Geographic Distribution of HIV Transmission Networks in the United States
Authors: Board Amy R. , Oster Alexandra M. , Song Ruiguang , Gant Zanetta , Linley Laurie , Watson Meg , Zhang Tianchi , France Anne Marie
Published: July 2020

Background:

Understanding geographic patterns of HIV transmission is critical to designing effective interventions. We characterized geographic proximity by transmission risk and urban–rural characteristics among people with closely related HIV strains suggestive of potential transmission relationships.

Methods:

We analyzed US National HIV Surveillance System data of people diagnosed between 2010 and 2016 with a reported HIV-1 partial polymerase nucleotide sequence. We used HIV TRAnsmission Cluster Engine (HIV-TRACE) to identify sequences linked at a genetic distance of ≤0.5%. For each linked person, we assessed median distances between counties of residence at diagnosis by transmission category and urban–rural classification, weighting observations to account for persons with multiple linked sequences.

Results:

There were 24,743 persons with viral sequence linkages to at least one other person included in this analysis. Overall, half (50.9%) of persons with linked viral sequences resided in different counties, and the median distance from persons with linked viruses was 11 km/7 miles [interquartile range (IQR), 0–145 km/90 miles]. Median distances were highest for men who have sex with men (MSM: 14 km/9 miles; IQR, 0–179 km/111 miles) and MSM who inject drugs, and median distances increased with increasing rurality (large central metro: 0 km/miles; IQR, 0–83 km/52 miles; nonmetro: 103 km/64 miles; IQR, 40 km/25 miles–316 km/196 miles).

Conclusion:

Transmission networks in the United States involving MSM, MSM who inject drugs, or persons living in small metro and nonmetro counties may be more geographically dispersed, highlighting the importance of coordinated health department efforts for comprehensive follow-up and linkage to care.
Course Review
Authors: Challoner Tom
Published: July 2020

The Hand and Wrist Sculpture Course, organized by the Surgical Sculpture Workshops and badged by the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS), is a 2-day innovative course aimed at trainees in plastic and orthopedic surgery, as well as therapists, teaching about the bony and soft tissue anatomy through a hands-on sculpting workshop for application in clinical work. The course is delivered by an expert faculty of hand surgeons with a keen interest in art and sculpture, and costs £300. The following review details the course and provides a detailed evaluation of the course.
Modified Use of Costal Cartilage in Asians for the Correction of Nostril Asymmetry in Unilateral Secondary Cleft Lip Nasal Deformity
Authors: Zhang Zhenyu , Huang Tony Chieh-Ting , He Yinhai , Li Shang , Li Zhengyong , Chen Junjie , Cen Ying , Qing Yong
Published: July 2020

Background

Weak alar cartilage and lack of soft tissue on the cleft side are considered to be the main critical factors leading to the asymmetry of bilateral nostrils. The costal cartilage can provide strong structural support and can be used to maintain long-term stability of nostril shape after surgical correction. With the advancement in rhinoplasty techniques, the application and understanding of costal cartilage in cleft lip nasal deformity is still on going. Herein, we present our technique of applying costal cartilage to provide nostril support and correct asymmetry in Asian patients with unilateral secondary cleft lip nasal deformity.

Methods

Ninety-seven patients who underwent nostril asymmetry correction from January 1, 2013, to October 31, 2018, were analyzed retrospectively. Modified integrative alar cartilage strut and diced nostril augmentation with costal cartilage were implemented to improve the collapsed and flat cleft-side nostril. The release and restoration of muscle and bone were also performed when required. Surgical outcomes were analyzed based on the comparison of nostril parameters, the shape and contour, and symmetry of bilateral nostrils after surgery. During postoperative follow-up, the patients' satisfactions with the corrective outcomes were also investigated.

Results

All patients received the corrective operations with complete survival of all implanted cartilages. The nostril width was narrower in postoperative group (P < 0.05). The nostril height and long axis angle were higher postoperatively (P < 0.05). After correction, the proportion of moderate type increased from 13.4% to 80.4%, whereas the proportion of horizontal type decreased from 86.6% to 17.5%. The symmetry score on the nostril parameters manifested the rate of high score (AS >3) in postoperative groups were 84.5%, 93.8%, and 87.6% for width, height, and angle of the long axis, respectively. They were higher compared with those of preoperative group (0%). More than 95% of the patients were satisfied with the overall aesthetic outcome of the surgery.

Conclusions

Through ameliorating its constructive technology and optimizing its filling form, the modified use of costal cartilage displayed excellent correction effects in the width, height, and long axis angle asymmetry of Asian patients' nostril. Precise and comprehensive rhinoplasty technique is the cornerstone for achieving satisfactory long-term aesthetic outcomes, especially in severe cases, such as secondary cleft lip nasal deformity.
A note on the Stokes phenomenon in flow under an elastic sheet
Authors: Lustri Christopher J. , Koens Lyndon , Pethiyagoda Ravindra
Published: August 2020

The Stokes phenomenon is a class of asymptotic behaviour that was first discovered by Stokes in his study of the Airy function. It has since been shown that the Stokes phenomenon plays a significant role in the behaviour of surface waves on flows past submerged obstacles. A detailed review of recent research in this area is presented, which outlines the role that the Stokes phenomenon plays in a wide range of free surface flow geometries. The problem of inviscid, irrotational, incompressible flow past a submerged step under a thin elastic sheet is then considered. It is shown that the method for computing this wave behaviour is extremely similar to previous work on computing the behaviour of capillary waves. Exponential asymptotics are used to show that free-surface waves appear on the surface of the flow, caused by singular fluid behaviour in the neighbourhood of the base and top of the step. The amplitude of these waves is computed and compared to numerical simulations, showing excellent agreements between the asymptotic theory and computational solutions.

This article is part of the theme issue ‘Stokes at 200 (part 2)’.
George Gabriel Stokes as a biologist
Authors: Ceredig Rhodri
Published: August 2020

It is universally acknowledged that George Gabriel Stokes (1819–1903) was a polymath who made major contributions to the fields of mathematics, chemistry, physics, fluidics and optics. However, his contributions to biology have received far less attention and this brief communication examines two of Stokes' major biological contributions, namely his description of the phenomenon of fluorescence and his studies on the changes in the colour of blood following oxidation and reduction. The paper on fluorescence is discussed because in it, Stokes demonstrates his wide-ranging biological knowledge and because the use of fluorescence is an invaluable experimental tool in biology. It was by developing the experimental approaches and equipment used to investigate fluorescence that Stokes then applied these to other investigations, including that of blood. From what we now know, what Stokes was describing in his paper on blood were the changes in the configuration of the haemoglobin molecule upon the acquisition and release of oxygen.

This article is part of the theme issue ‘Stokes at 200 (part 2)'.
Roseobacter cerasinus sp. nov., isolated from a fish farm
Authors: Muramatsu So , Kanamuro Masataka , Sato-Takabe Yuki , Hirose Setsuko , Muramatsu Yuki , Takaichi Shinichi , Hanada Satoshi
Published: July 2020

An obligate aerobic and bacteriochlorophyll a-containing bacterium, designated strain AI77T, was isolated from a fish farm in Uwa Sea, Japan. Cells were Gram-stain-negative, coccoid- to oval-shaped, and showed no motility. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain AI77T is a member of the genus

Roseobacter

and closely related to

Roseobacter ponti

MM-7T (97.8 %),

Roseobacter denitrificans

OCh 114T (97.3 %) and

Roseobacter litoralis

OCh 149T (97.3 %). The G+C content of strain AI77T was 61.0 mol%. The average amino acid identity values of the genome in strain AI77T with those in

R. denitrificans

OCh 114T and

R. litoralis

OCh 149T were 73.26 % (SD 16.46) and 72.63 % (SD 16.76), respectively. The digital DNA–DNA hybridization values of strain AI77T with the type strains

R. denitrificans

OCh 114T and

R. litoralis

OCh 149T were 18.70 and 18.50 %, respectively. The dominant fatty acids (>10 % of total fatty acids) of AI77T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and saturated fatty acid C16 : 0. The sole respiratory quinone was ubiquinone-10. The predominant polar lipids were phosphatidylcholine, phosphatidylglycerol and diphosphatidylglycerol. Based on the genetic and phenotypic data obtained herein, we conclude that strain AI77T represents a new species of the genus

Roseobacter

, for which we propose the name Roseobacter cerasinus sp. nov.; the type strain is AI77T (=DSM 110091T=NBRC 114115T).
Developing Small Molecules that Inhibit K-Ras/GTP Binding Based on New Affinity Measurements
Authors: Carta Luca , Hutcheson Rebecca , Davis Simon A. , Rudolph Michael J. , Reynolds Charles H. , Quick Matthias , Williams Theresa M. , Schmertzler Michael , Hadari Yaron R.
Published: July 2020

RASgenes encode small GTPases essential for proliferation, differentiation, and survival of mammalian cells.RASgene mutations are associated with approximately 30% of all human cancers. However, based on measurements reported three decades ago of Ras protein affinities to GTP in the 10-20 picomolar range, it has been accepted in the scientific and medical communities that Ras proteins are undruggable targets. Here, we report MicroScale Thermophoresis and scintillation proximity assay measurements of the affinity of K-Ras and several K-Ras mutants for GTP in the range of 200 nanomolar, a 10,000-fold difference from that previously reported, and the identification of over 400 small molecules that block GTP binding to K-Ras. Focusing on two of those molecules, we report small molecule inhibition of Ras downstream signaling and cellular proliferation in human pancreatic and non-small cell lung cancer cells expressing wild type and K-Ras G12C, G12D and G12S, and N-Ras Q61K mutants.
Classification of complex emotions using EEG and virtual environment: proof of concept and therapeutic implication
Authors: De Filippi Eleonora , Wolter Mara , Melo Bruno , Tierra-Criollo Carlos J. , Bortolini Tiago , Deco Gustavo , Moll Jorge
Published: July 2020

During the last decades, neurofeedback training for emotional self-regulation has received significant attention from both the scientific and clinical communities. However, most studies have focused on broader emotional states such as “negative vs. positive”, primarily due to our poor understanding of the functional anatomy of more complex emotions at the electrophysiological level. Our proof-of-concept study aims at investigating the feasibility of classifying two complex emotions that have been implicated in mental health, namely tenderness and anguish, using features extracted from the electroencephalogram (EEG) signal in healthy participants. Electrophysiological data were recorded from fourteen participants during a block-designed experiment consisting of emotional self-induction trials combined with a multimodal virtual scenario. For the within-subject classification, the linear Support Vector Machine was trained with two sets of samples: random cross-validation of the sliding windows of all trials; and 2) strategic cross-validation, assigning all the windows of one trial to the same fold. Spectral features, together with the frontal-alpha asymmetry, were extracted using Complex Morlet Wavelet analysis. Classification results with these features showed an accuracy of 79.3% on average when doing random cross-validation, and 73.3% when applying strategic cross-validation. We extracted a second set of features from the amplitude time-series correlation analysis, which significantly enhanced random cross-validation accuracy while showing similar performance to spectral features when doing strategic cross-validation. These results suggest that complex emotions show distinct electrophysiological correlates, which paves the way for future EEG-based, real-time neurofeedback training of complex emotional states.

Significance statement

There is still little understanding about the correlates of high-order emotions (i.e., anguish and tenderness) in the physiological signals recorded with the EEG. Most studies have investigated emotions using functional magnetic resonance imaging (fMRI), including the real-time application in neurofeedback training. However, concerning the therapeutic application, EEG is a more suitable tool with regards to costs and practicability. Therefore, our proof-of-concept study aims at establishing a method for classifying complex emotions that can be later used for EEG-based neurofeedback on emotion regulation. We recorded EEG signals during a multimodal, near-immersive emotion-elicitation experiment. Results demonstrate that intraindividual classification of discrete emotions with features extracted from the EEG is feasible and may be implemented in real-time to enable neurofeedback.
NEURAL ENCODING OF FELT AND IMAGINED TOUCH WITHIN HUMAN POSTERIOR PARIETAL CORTEX
Authors: Chivukula Srinivas , Zhang Carey , Aflalo Tyson , Jafari Matiar , Pejsa Kelsie , Pouratian Nader , Andersen Richard A.
Published: July 2020

In the human posterior parietal cortex (PPC), single units encode high-dimensional information withpartially mixedrepresentations that enable small populations of neurons to encode many variables relevant to movement planning, execution, cognition, and perception. Here we test whether a PPC neuronal population previously demonstrated to encode visual and motor information is similarly selective in the somatosensory domain. We recorded from 1423 neurons within the PPC of a human clinical trial participant during objective touch presentation and during tactile imagery. Neurons encoded experienced touch with bilateral receptive fields, organized by body part, and covered all tested regions. Tactile imagery evoked body part specific responses that shared a neural substrate with experienced touch. Our results are the first neuron level evidence of touch encoding in human PPC and its cognitive engagement during tactile imagery which may reflect semantic processing, sensory anticipation, and imagined touch.
Impact of reduction of susceptibility to SARS-CoV-2 on epidemic dynamics in four early-seeded metropolitan regions
Authors: Barrett T. J. , Patterson K. C. , James T. M. , Krüger P.
Published: July 2020

As we enter a chronic phase of the SARS-CoV-2 pandemic, with uncontrolled infection rates in many places, relative regional susceptibilities are a critical unknown for policy planning. Tests for SARS-CoV-2 infection or antibodies are indicative but unreliable measures of exposure. Here instead, for four highly-affected countries, we determine population susceptibilities by directly comparing country-wide observed epidemic dynamics data with that with their main metropolitan regions. We find significant susceptibility reductions in the metropolitan regions as a result of earlier seeding, with a relatively longer phase of exponential growth before the introduction of public health interventions. During the post-growth phase, the lower susceptibility of these regions contributed to the decline in cases, independent of intervention effects. Forward projections indicate that non-metropolitan regions will be more affected during recurrent epidemic waves compared with the initially heavier-hit metropolitan regions. Our findings have consequences for disease forecasts and resource utilisation.
Neuropeptidome regulation after baculovirus infection. A focus on proctolin and its relevance in locomotion and digestion
Authors: Llopis-Giménez Angel , Parenti Stefano , Han Yue , Ros Vera I.D. , Herrero Salvador
Published: July 2020

Baculoviruses constitute a large group of invertebrate DNA viruses, predominantly infecting larvae of the insect order Lepidoptera. During a baculovirus infection, the virus spreads throughout the insect body producing a systemic infection in multiple larval tissues. Some behavioral and physiological changes in lepidopteran larvae have been described following a baculovirus infection and those changes could be connected with alterations in the host’s central nervous system (CNS). As a main component of the CNS, neuropeptides are small protein-like molecules functioning as neurohormones, neurotransmitters or neuromodulators. These peptides are involved in regulating animal physiology and behaviour and could also be targeted by baculoviruses in order to achieve host behavioural manipulations leading to increased viral fitness. In this study, we have investigated the effect of aSpodoptera exigua multiple nucleopolyhedrovirus(SeMNPV) infection on the neuropeptidome gene expression ofSpodoptera exigualarval heads and brains. Expression of the gene encoding the neuropeptide proctolin was severely downregulated following infection and was chosen for further analysis. A recombinantAutographa californica multiple nucleopolyhedrovirus(AcMNPV) overexpressing theS. exigua proctolingene was generated and used in bioassays usingS. exigualarvae to study its influence on the viral infection. AcMNPV-proctolin infected larvae showed less locomotion activity and suffered a loss of weight compared to larvae infected with wild type AcMNPV or mock-infected larvae. These results provide additional information on the role ofproctolinduring a baculovirus infection, and offers a novel hypothesis for the molecular bases for the behavioral changes associated with a baculovirus infection.
Evaluation of Polygenic Prediction Methodology within a Reference-Standardized Framework
Authors: Pain Oliver , Glanville Kylie P. , Hagenaars Saskia P. , Selzam Saskia , Fürtjes Anna E. , Gaspar Héléna A. , Coleman Jonathan R. I. , Rimfeld Kaili , Breen Gerome , Plomin Robert , Folkersen Lasse , Lewis Cathryn M.
Published: July 2020

Background

The predictive utility of polygenic scores is increasing, and many polygenic scoring methods are available, but it is unclear which method performs best. This study evaluates the predictive utility of polygenic scoring methods within a reference-standardized framework, which uses a common set of variants and reference-based estimates of linkage disequilibrium and allele frequencies to construct scores.

Methods

Eight polygenic score methods were tested: p-value thresholding and clumping (pT+clump), SBLUP, lassosum, LDPred1, LDPred2, PRScs, DBSLMM and SBayesR, evaluating their performance to predict outcomes in UK Biobank and the Twins Early Development Study (TEDS). Strategies to identify optimal p-value threshold and shrinkage parameters were compared, including 10-fold cross validation, pseudovalidation and infinitesimal models (with no validation sample), and multi-polygenic score elastic net models.

Results

LDPred2, lassosum and PRScs performed strongly using 10-fold cross-validation to identify the most predictive p-value threshold or shrinkage parameter, giving a relative improvement of 16-18% over pT+clump in the correlation between observed and predicted outcome values. Using pseudovalidation, the best methods were PRScs and DBSLMM, with a relative improvement of >10% over other pseudovalidation and infinitesimal methods (lassosum, SBLUP, SBayesR, LDPred1, LDPred2). PRScs pseudovalidation was only 3% worse than the best polygenic score identified by 10-fold cross validation. Elastic net models containing polygenic scores based on a range of parameters consistently improved prediction over any single polygenic score.

Conclusion

Within a reference-standardized framework, the best polygenic prediction was achieved using LDPred2, lassosum and PRScs, modeling multiple polygenic scores derived using multiple parameters. This study will help researchers performing polygenic score studies to select the most powerful and predictive analysis methods.